RESUMEN
Phototherapy is a promising antitumor modality, which consists of photothermal therapy (PTT) and photodynamic therapy (PDT). However, the efficacy of phototherapy is dramatically hampered by local hypoxia in tumors, overexpression of indoleamine 2,3-dioxygenase (IDO) and programmed cell death ligand-1 (PD-L1) on tumor cells. To address these issues, self-assembled multifunctional polymeric micelles (RIMNA) were developed to co-deliver photosensitizer indocyanine green (ICG), oxygenator MnO2, IDO inhibitor NLG919, and toll-like receptor 4 agonist monophosphoryl lipid A (MPLA). It is worth noting that RIMNA polymeric micelles had good stability, uniform morphology, superior biocompatibility, and intensified PTT/PDT effect. What's more, RIMNA-mediated IDO inhibition combined with programmed death receptor-1 (PD-1)/PD-L1 blockade considerably improved immunosuppression and promoted immune activation. RIMNA-based photoimmunotherapy synergized with PD-1 antibody could remarkably inhibit primary tumor proliferation, as well as stimulate the immunity to greatly suppress lung metastasis and distant tumor growth. This study offers an efficient method to reinforce the efficacy of phototherapy and alleviate immunosuppression, thereby bringing clinical benefits to cancer treatment.
Asunto(s)
Neoplasias del Colon , Inmunoterapia , Micelas , Fototerapia , Polímeros , Receptor de Muerte Celular Programada 1 , Animales , Neoplasias del Colon/terapia , Neoplasias del Colon/inmunología , Neoplasias del Colon/tratamiento farmacológico , Ratones , Inmunoterapia/métodos , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Polímeros/química , Línea Celular Tumoral , Fototerapia/métodos , Verde de Indocianina/química , Verde de Indocianina/uso terapéutico , Verde de Indocianina/farmacología , Ratones Endogámicos BALB C , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Fotoquimioterapia/métodos , Femenino , Humanos , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/metabolismo , Lípido A/análogos & derivadosRESUMEN
Gene transfection, defined by the delivery of nucleic acids into cellular compartments, stands as a crucial procedure in gene therapy. While branched polyethylenimine (PEI) is widely regarded as the "gold standard" for nonviral vectors, its cationic nature presents several issues, including nonspecific protein adsorption and notable cytotoxicity. Additionally, it often fails to achieve high transfection efficiency, particularly with hard-to-transfect cell types. To overcome these challenges associated with PEI as a vector for plasmid DNA (pDNA), the photothermal agent indocyanine green (ICG) is integrated with PEI and pDNA to form the PEI/ICG/pDNA (PI/pDNA) complex for more efficient and safer gene transfection. The negatively charged ICG serves a dual purpose: neutralizing PEI's excessive positive charges to reduce cytotoxicity and, under near-infrared irradiation, inducing local heating that enhances cell membrane permeability, thus facilitating the uptake of PI/pDNA complexes to boost transfection efficiency. Using pDNA encoding vascular endothelial growth factor as a model, our system shows enhanced transfection efficiency in vitro for hard-to-transfect endothelial cells, leading to improved cell proliferation and migration. Furthermore, in vivo studies reveal the therapeutic potential of this system in accelerating the healing of infected wounds by promoting angiogenesis and reducing inflammation. This approach offers a straightforward and effective method for gene transfection, showing potentials for tissue engineering and cell-based therapies.
Asunto(s)
Verde de Indocianina , Plásmidos , Polietileneimina , Transfección , Verde de Indocianina/química , Verde de Indocianina/farmacología , Polietileneimina/química , Humanos , Transfección/métodos , Animales , Plásmidos/genética , Plásmidos/metabolismo , Plásmidos/química , Ratones , ADN/química , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Células Endoteliales de la Vena Umbilical Humana , Proliferación Celular/efectos de los fármacosRESUMEN
Antibody therapy of anti-HER2 monoclonal antibody (mAb) has been an important strategy in treating HER2-positive cancers. However, the efficacy is restricted by many factors, including the level of HER2 expressed by tumor cells and antibody resistance. To overcome these and boost the efficacy, a novel nanoparticle (NP) was constructed in this study for combined antibody therapy of antibody and photothermal therapy (PTT). This novel NP was assembled from 1-pyrenecarboxylic acid (PCA) functionalized anti-HER2 mAb and indocyanine green (ICG), a photothermal transduction agents (PTA), by non-covalent interactions, which was named as Anti-HER2 mAb-pyrene-indocyanine green (H-P-I). Notably, the constructed H-P-I NP not only maintained the affinity and cytotoxicity of anti-HER2 mAb, but also exhibited high photothermal conversion efficiency mediated by ICG. Both in vitro and in vivo assessments confirmed that compared with monotherapy of antibody or ICG, H-P-I demonstrated preferable efficacy in treating HER2-positive cancers. Further biochemistry analysis and pathological analysis ensured the biosafety of H-P-I administration. Taked together, this study proposes a feasible method for constructing tumor-targeted nano PTA based on anti-HER2 mAb through supramolecular self-assembly strategy, achieving synergistic antibody photothermal anticancer treatment, which has the potential to be a promising candidate for combination therapy of HER2-positive cancers.
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Inmunoconjugados , Terapia Fototérmica , Receptor ErbB-2 , Receptor ErbB-2/metabolismo , Receptor ErbB-2/inmunología , Receptor ErbB-2/antagonistas & inhibidores , Humanos , Terapia Fototérmica/métodos , Animales , Inmunoconjugados/farmacología , Inmunoconjugados/química , Inmunoconjugados/uso terapéutico , Ratones , Línea Celular Tumoral , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/química , Nanopartículas/química , Verde de Indocianina/química , Verde de Indocianina/farmacología , Verde de Indocianina/uso terapéutico , Femenino , Neoplasias/terapia , Neoplasias/inmunologíaRESUMEN
Subcutaneous (SC) administration of chemotherapeutics combined with near-infrared (NIR) light activation can effectively target skin tumors by triggering localized drug release and enhancing cytotoxic effects. In this study, we developed NIR-responsive indocyanine green (ICG) and the chemotherapeutic agent doxorubicin (Dox) loaded into gelatin nanoparticles (NPs) for SC delivery in a skin tumor-bearing mouse model. Histological examination (hematoxylin and eosin staining) confirmed the successful delivery and swelling behavior of the Dox/ICG-loaded gelatin NPs at the SC site. In vitro and in vivo experiments demonstrated that NIR activation of the Dox/ICG-loaded gelatin NPs generated significant photothermal heat (48 and 46 °C), leading to targeted drug release and a substantial reduction in skin tumor size (from 15 to 3 mm3). Our findings suggest that this dual-modality approach of SC chemotherapeutic administration and NIR-triggered photothermal therapy can concentrate cytotoxic drugs at the tumor site, offering a promising strategy for improving skin cancer treatment.
Asunto(s)
Doxorrubicina , Gelatina , Verde de Indocianina , Rayos Infrarrojos , Ensayo de Materiales , Nanopartículas , Neoplasias Cutáneas , Gelatina/química , Doxorrubicina/química , Doxorrubicina/farmacología , Doxorrubicina/administración & dosificación , Animales , Nanopartículas/química , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Ratones , Verde de Indocianina/química , Verde de Indocianina/administración & dosificación , Verde de Indocianina/farmacología , Tamaño de la Partícula , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Supervivencia Celular/efectos de los fármacos , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/administración & dosificación , Humanos , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacología , Antibióticos Antineoplásicos/administración & dosificación , Proliferación Celular/efectos de los fármacos , Sistemas de Liberación de Medicamentos , Ratones Endogámicos BALB C , Línea Celular Tumoral , Terapia Fototérmica , Liberación de Fármacos , Portadores de Fármacos/química , Inyecciones SubcutáneasRESUMEN
Abnormal amyloid ß-protein (Aß42) fibrillation is a key event in Alzheimer's disease (AD), and photodynamic therapy (PDT) possesses great potential in modulating Aß42 self-assembly. However, the poor blood-brain barrier (BBB) penetration, low biocompatibility, and limited tissue penetration depth of existing photosensitizers limit the progress of photo-oxidation strategies. In this paper, novel indocyanine green-modified graphene quantum dot nano-assemblies (NBGQDs-ICGs) were synthesized based on a molecular assembly strategy of electrostatic interactions for PDT inhibition of Aß42 self-assembly process and decomposition of preformed fibrils under near-infrared light. Combining the small-size structure of graphene quantum dots and the near-infrared light-responsive properties of ICGs, the NBGQDs-ICGs could achieve BBB penetration under 808â¯nm irradiation. More importantly, the neuroprotective mechanism of NBGQDs-ICG was studied for the first time by AFM, which effectively weakened the adhesion of Aß42 aggregates to the cell surface by blocking the interaction between Aß42 and the cell membrane, and restored the mechanical stability and adhesion of the neuron membrane. Meanwhile, NBGQDs-ICG promoted phagocytosis of Aß42 by microglia. In addition, the good biocompatibility and stability ensured the biosafety of NBGQDs-ICG in future clinical applications. We anticipate that such multifunctional nanocomponents may provide promising avenues for the development of novel AD inhibitors.
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Péptidos beta-Amiloides , Barrera Hematoencefálica , Puntos Cuánticos , Péptidos beta-Amiloides/metabolismo , Péptidos beta-Amiloides/química , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/efectos de los fármacos , Puntos Cuánticos/química , Humanos , Animales , Grafito/química , Grafito/farmacología , Fragmentos de Péptidos/química , Fragmentos de Péptidos/metabolismo , Tamaño de la Partícula , Verde de Indocianina/química , Verde de Indocianina/farmacología , Fagocitosis/efectos de los fármacos , Carbono/química , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Propiedades de SuperficieRESUMEN
Reactive oxygen species (ROS) are widely considered to the effective therapeutics for fighting bacterial infections especially those associated with biofilm. However, biofilm microenvironments including hypoxia, limited H2O2, and high glutathione (GSH) level seriously limit the therapeutic efficacy of ROS-based strategies. Herein, we have developed an acidic biofilm microenvironment-responsive antibacterial nanoplatform consisting of copper-dopped bovine serum albumin (CBSA) loaded with copper peroxide (CuO2) synthesized in situ and indocyanine green (ICG). The three-in-one nanotherapeutics (CuO2/ICG@CBSA) are capable of releasing Cu2+ and H2O2 in a slightly acidic environment, where Cu2+ catalyzes the conversion of H2O2 into hydroxyl radical (â¢OH) and consumes the highly expressed GSH to disrupt the redox homeostasis. With the assistance of an 808 nm laser, the loaded ICG not only triggers the production of singlet oxygen (1O2) by a photodynamic process, but also provides photonic hyperpyrexia that further promotes the Fenton-like reaction for enhancing â¢OH production and induces thermal decomposition of CuO2 for the O2-self-supplying 1O2 generation. The CuO2/ICG@CBSA with laser irradiation demonstrates photothermal-augmented multi-mode synergistic bactericidal effect and is capable of inhibiting biofilm formation and eradicating the biofilm bacteria. Further in vivo experiments suggest that the CuO2/ICG@CBSA can effectively eliminate wound infections and accelerate wound healing. The proposed three-in-one nanotherapeutics with O2/H2O2-self-supplied ROS generating capability show great potential in treating biofilm-associated bacterial infections. STATEMENT OF SIGNIFICANCE: Here, we have developed an acidic biofilm microenvironment-responsive nanoplatform consisting of copper-dopped bovine serum albumin (CBSA) loaded with copper peroxide (CuO2) synthesized in situ and indocyanine green (ICG). The nanotherapeutics (CuO2/ICG@CBSA) are capable of releasing Cu2+ and H2O2 in an acidic environment, where Cu2+ catalyzes the conversion of H2O2 into â¢OH and consumes the overexpressed GSH to improve oxidative stress. With the aid of an 808 nm laser, ICG provides photonic hyperpyrexia for enhancing â¢OH production, and triggers O2-self-supplying 1O2 generation. CuO2/ICG@CBSA with laser irradiation displays photothermal-augmented multi-mode antibacterial and antibiofilm effect. Further in vivo experiments prove that CuO2/ICG@CBSA effectively eliminates wound infection and promotes wound healing. The proposed three-in-one nanotherapeutics show great potential in treating biofilm-associated bacterial infections.
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Biopelículas , Cobre , Glutatión , Verde de Indocianina , Especies Reactivas de Oxígeno , Albúmina Sérica Bovina , Biopelículas/efectos de los fármacos , Animales , Cobre/química , Cobre/farmacología , Glutatión/metabolismo , Albúmina Sérica Bovina/química , Especies Reactivas de Oxígeno/metabolismo , Verde de Indocianina/química , Verde de Indocianina/farmacología , Peróxido de Hidrógeno/química , Ratones , Antibacterianos/farmacología , Antibacterianos/química , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/fisiología , Concentración de Iones de HidrógenoRESUMEN
The hypoxic environment within a solid tumor is a limitation to the effectiveness of photodynamic therapy. Here, we demonstrate the use of oxygen generating nanozymes (CeO2, Fe3O4, and MnO2) to improve the photodynamic effect. The optimized combination of process parameters for irradiation was obtained using the Box Behnken experimental design. Indocyanine green, IR 820, and their different combinations with oxygen generators were studied for their effect on oral carcinoma. Dynamic light scattering technique showed the average particle size of CeO2, MnO2, and Fe3O4 to be 211 ± 16, and 157 ± 28, 143 ± 19 nm with PDI of 0.23, 0.28 and 0.20 and a zeta potential of -2.6 ± 0.45, -2.4 ± 0.60 and -6.1 ± 0.23 mV, respectively. The formation of metal oxides was confirmed using UV-visible, FTIR, and X-ray photon spectroscopies. The amount of dissolved oxygen produced by CeO2, MnO2, and Fe3O4 in the presence of H2O2 within 2 min was 1.7 ± 0.15, 1.7 ± 0.16, and 1.4 ± 0.12 mg/l, respectively. Growth inhibition studies in the FaDu oral carcinoma spheroid model showed a significant (P < 0.05) increase in growth reduction from 81 ± 2.9 and 88 ± 2.1% to 97 ± 1.2 and 99 ± 1.0% for ICG and IR 820, respectively, after irradiation (808 nm laser, 1 W/cm2, 5 min) in the presence of CeO2 (25 µg/ml). In conclusion, oxygen-generating nanozymes can improve the photodynamic effect of ICG and IR 820.
Asunto(s)
Cerio , Verde de Indocianina , Compuestos de Manganeso , Neoplasias de la Boca , Óxidos , Oxígeno , Verde de Indocianina/química , Verde de Indocianina/farmacología , Humanos , Compuestos de Manganeso/química , Compuestos de Manganeso/farmacología , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Oxígeno/química , Oxígeno/metabolismo , Óxidos/química , Óxidos/farmacología , Cerio/química , Cerio/farmacología , Línea Celular Tumoral , Fotoquimioterapia , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Peróxido de Hidrógeno/química , Tamaño de la Partícula , Supervivencia Celular/efectos de los fármacosRESUMEN
The ground-breaking combination of photodynamic therapy (PDT) and photothermal therapy (PTT) has attracted much attention in medical fields as an effective method for fighting cancer. However, evidence suggests that the therapy efficiency is still limited by shallow light penetration depth and poor photosensitizer loading capacity. Herein, we constructed an upconversion nanoparticle@Zr-based metal-organic framework@indocyanine green molecule (UCNPs@ZrMOF@ICG) nanocomposite to integrate 1532 nm light-triggered PDT and 808 nm light-mediated PTT. NaLnF4 nanoparticles are designed to emit upconversion luminescence (UCL) under 1532 nm laser excitation, which is consistent with the absorption spectra of the ZrMOF. Benefiting from the excellent energy transfer efficiency, the ZrMOF can absorb visible light from the UCNPs and then catalyze O2 into 1O2 for deep tissue PDT. To achieve combination therapy, the clinically approved ICG nanocomposite was introduced as a photothermal agent for PTT under 808 nm laser irradiation, and the photothermal conversion efficiency was calculated to be â¼28%. The designed nanosystems facilitate efficient deep-tissue tumor treatment by integrating PDT with PTT. Ultimately, this study creates a multifunctional nanocomposite by combining 1532 nm light-triggered deep tissue PDT and near-infrared (NIR) light-driven PTT for personalized cancer therapy.
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Rayos Infrarrojos , Elementos de la Serie de los Lantanoides , Estructuras Metalorgánicas , Fotoquimioterapia , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Estructuras Metalorgánicas/síntesis química , Humanos , Ratones , Elementos de la Serie de los Lantanoides/química , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/síntesis química , Catálisis , Tamaño de la Partícula , Terapia Fototérmica , Verde de Indocianina/química , Verde de Indocianina/farmacología , Nanopartículas/química , Supervivencia Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Proliferación Celular/efectos de los fármacos , Nanocompuestos/química , Nanocompuestos/uso terapéuticoRESUMEN
Microcarrier is a promising drug delivery system demonstrating significant value in treating cancers. One of the main goals is to devise microcarriers with ingenious structures and functions to achieve better therapeutic efficacy in tumors. Here, inspired by the nucleus-cytoplasm structure of cells and the material exchange reaction between them, we develop a type of biorthogonal compartmental microparticles (BCMs) from microfluidics that can separately load and sequentially release cyclooctene-modified doxorubicin prodrug (TCO-DOX) and tetrazine-modified indocyanine green (Tz-ICG) for tumor therapy. The Tz-ICG works not only as an activator for TCO-DOX but also as a photothermal agent, allowing for the combination of bioorthogonal chemotherapy and photothermal therapy (PTT). Besides, the modification of DOX with cyclooctene significantly decreases the systemic toxicity of DOX. As a result, the developed BCMs demonstrate efficient in vitro tumor cell eradication and exhibit notable tumor growth inhibition with favorable safety. These findings illustrate that the formulated BCMs establish a platform for bioorthogonal prodrug activation and localized delivery, holding significant potential for cancer therapy and related applications.
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Doxorrubicina , Sistemas de Liberación de Medicamentos , Verde de Indocianina , Terapia Fototérmica , Profármacos , Doxorrubicina/farmacología , Doxorrubicina/química , Terapia Fototérmica/métodos , Humanos , Profármacos/farmacología , Profármacos/química , Animales , Verde de Indocianina/química , Verde de Indocianina/farmacología , Ratones , Sistemas de Liberación de Medicamentos/métodos , Línea Celular Tumoral , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Ciclooctanos/química , Ciclooctanos/farmacología , Ratones Endogámicos BALB C , Antineoplásicos/farmacología , Antineoplásicos/química , FemeninoRESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) is a highly malignant tumor known for its hypoxic environment, which contributes to resistance against the anticancer drug Sorafenib (SF). Addressing SF resistance in HCC requires innovative strategies to improve tumor oxygenation and effectively deliver therapeutics. RESULTS: In our study, we explored the role of KPNA4 in mediating hypoxia-induced SF resistance in HCC. We developed hemoglobin nanoclusters (Hb-NCs) capable of carrying oxygen, loaded with indocyanine green (ICG) and SF, named HPRG@SF. In vitro, HPRG@SF targeted HCC cells, alleviated hypoxia, suppressed KPNA4 expression, and enhanced the cytotoxicity of PDT against hypoxic, SF-resistant HCC cells. In vivo experiments supported these findings, showing that HPRG@SF effectively improved the oxygenation within the tumor microenvironment and countered SF resistance through combined photodynamic therapy (PDT). CONCLUSION: The combination of Hb-NCs with ICG and SF, forming HPRG@SF, presents a potent strategy to overcome drug resistance in hepatocellular carcinoma by improving hypoxia and employing PDT. This approach not only targets the hypoxic conditions that underlie resistance but also provides a synergistic anticancer effect, highlighting its potential for clinical applications in treating resistant HCC.
Asunto(s)
Carcinoma Hepatocelular , Hemoglobinas , Verde de Indocianina , Neoplasias Hepáticas , Fotoquimioterapia , Sorafenib , Microambiente Tumoral , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Microambiente Tumoral/efectos de los fármacos , Humanos , Fotoquimioterapia/métodos , Animales , Hemoglobinas/farmacología , Línea Celular Tumoral , Sorafenib/farmacología , Sorafenib/uso terapéutico , Ratones , Verde de Indocianina/química , Verde de Indocianina/farmacología , Verde de Indocianina/uso terapéutico , Ratones Desnudos , Ratones Endogámicos BALB C , Antineoplásicos/farmacología , Antineoplásicos/química , alfa Carioferinas/metabolismo , Resistencia a Antineoplásicos/efectos de los fármacos , Nanopartículas/químicaRESUMEN
Near-infrared (NIR) phototherapies offer noninvasive, cost-effective solutions for treating tumors and microbial infections. However, organic NIR dyes commonly used suffer from solubility and stability issues requiring frequent dosing. We address this challenge by exploring the bacteriophage-mediated enhancement of NIR dye properties. Upon encapsulation within phage nanosomes, IR780 and Indocyanine green (ICG), with similar optical properties but distinct water solubility and exhibit enhanced UV-vis absorbance and photothermal transduction efficacy compared to liposomes. Experimental characterization corroborated with all-atom molecular dynamics simulations imprints the nanoscale structure, solubility, dynamics, and binding of these NIR dye molecules to the membrane and protein molecules present in Phage capsid. These NIR dye-loaded phage nanosomes, coencapsulated with mitoxantrone, demonstrate enhanced anticancer activity, and when combined with amphotericin B, these dye molecules exhibit superior photothermal effects against fungal infections. Our findings present a simple and efficient approach for tuning the photothermal performance of existing NIR dyes through a rational design for enhanced therapeutic outcomes.
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Verde de Indocianina , Rayos Infrarrojos , Verde de Indocianina/química , Verde de Indocianina/farmacología , Humanos , Nanomedicina Teranóstica/métodos , Colorantes/química , Colorantes/farmacología , Indoles/química , Indoles/farmacología , Mitoxantrona/química , Mitoxantrona/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Simulación de Dinámica MolecularRESUMEN
Indocyanine green (ICG), the only near-infrared (NIR) dye approved for clinical use, has received increasing attention as a theranostic agent wherein diagnosis (fluorescence) is combined with therapy (phototherapy), but suffers rapid hepatic clearance, poor photostability, and limited accumulation at tumor sites. Here we report that dimerized ICG can self-assemble to form zwitterionic nanoparticles (ZN-dICG), which generate fluorescence self-quenching but exhibit superior photothermal and photodynamic properties over ICG. The zwitterionic moieties confer ZN-dICG an ultralow critical micelle concentration and high colloidal stability with low non-specific binding in vivo. In addition, ZN-dICG can respond to the over-generated reactive oxygen species (ROSs) and dissociate to restore NIR fluorescence of ICG, amplifying the sensitivity via albumin binding for low-background imaging of tumors. Following systemic administration, ZN-dICG accumulated in tumors of xenograft-bearing mice for imaging primary and metastatic tumors, and induced tumor ablation under laser irradiation. The discovery of ZN-dICG would contribute to the design of translational phototheranostic platform with high biocompatibility. STATEMENT OF SIGNIFICANCE: Indocyanine green (ICG) has been extensively studied as a phototheranostic agent that combines imaging with phototherapies, but it suffers from rapid hepatic clearance, poor photostability, and limited accumulation at tumor sites. Here, we report a strategy to construct ICG dimers (ICG-tk-ICG) by conjugating two ICG molecules via a thioketal bond, which can self-assemble into zwitterionic nanoparticles (ZN-dICG) at ultralow critical micelle concentrations, exhibiting superior photothermal and photodynamic properties over ICG. ZN-dICG responds to the over-generated ROS in tumors and dissociates to restore the NIR fluorescence of ICG, enhancing the sensitivity via albumin binding for low-background imaging of tumors. This study offers a supramolecular strategy that may potentiate the clinical translation of ICG in imaging-guided cancer phototherapy.
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Verde de Indocianina , Nanopartículas , Fototerapia , Verde de Indocianina/química , Verde de Indocianina/farmacología , Animales , Nanopartículas/química , Humanos , Ratones , Fototerapia/métodos , Dimerización , Ratones Desnudos , Línea Celular Tumoral , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Neoplasias/patología , Ratones Endogámicos BALB C , Femenino , Imagen Óptica/métodosRESUMEN
Introduction: Glioblastoma multiforme (GBM), a highly invasive and prognostically challenging brain cancer, poses a significant hurdle for current treatments due to the existence of the blood-brain barrier (BBB) and the difficulty to maintain an effective drug accumulation in deep GBM lesions. Methods: We present a biomimetic nanoplatform with angiopep-2-modified macrophage membrane, loaded with indocyanine green (ICG) templated self-assembly of SN38 (AM-NP), facilitating active tumor targeting and effective blood-brain barrier penetration through specific ligand-receptor interaction. Results: Upon accumulation at tumor sites, these nanoparticles achieved high drug concentrations. Subsequent combination of laser irradiation and release of chemotherapy agent SN38 induced a synergistic chemo-photothermal therapy. Compared to bare nanoparticles (NPs) lacking cell membrane encapsulation, AM-NPs significantly suppressed tumor growth, markedly enhanced survival rates, and exhibited excellent biocompatibility with minimal side effects. Conclusion: This NIR-activatable biomimetic camouflaging macrophage membrane-based nanoparticles enhanced drug delivery targeting ability through modifications of macrophage membranes and specific ligands. It simultaneously achieved synergistic chemo-photothermal therapy, enhancing treatment effectiveness. Compared to traditional treatment modalities, it provided a precise, efficient, and synergistic method that might have contributed to advancements in glioblastoma therapy.
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Barrera Hematoencefálica , Neoplasias Encefálicas , Liberación de Fármacos , Glioblastoma , Verde de Indocianina , Nanopartículas , Terapia Fototérmica , Glioblastoma/terapia , Glioblastoma/tratamiento farmacológico , Glioblastoma/metabolismo , Animales , Verde de Indocianina/química , Verde de Indocianina/farmacocinética , Verde de Indocianina/farmacología , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/metabolismo , Humanos , Línea Celular Tumoral , Ratones , Nanopartículas/química , Terapia Fototérmica/métodos , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Irinotecán/farmacocinética , Irinotecán/química , Irinotecán/farmacología , Péptidos/química , Péptidos/farmacología , Péptidos/farmacocinética , Rayos Infrarrojos , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacocinética , Materiales Biomiméticos/farmacología , Sistemas de Liberación de Medicamentos/métodos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones Desnudos , Terapia Combinada/métodosRESUMEN
There is an urgent need to develop phototherapeutic agents with imaging capabilities to assess the treatment process and efficacy in real-time during cancer phototherapy for precision cancer therapy. The safe near-infrared (NIR) fluorescent dyes have garnered significant attention and are desirable for theranostics agents. However, until now, achieving excellent photostability and fluorescence (FL) imaging capability in aggregation-caused quenching (ACQ) dyes remains a big challenge. Here, for the only FDA-approved NIR dye, indocyanine green (ICG), we developed a dual-ferrocene (Fc) chimeric nanonetwork ICG@HFFC based on the rigid-flexible strategy through one-step self-assembly, which uses rigid Fc-modified hyaluronic acid (HA) copolymer (HA-Fc) and flexible octadecylamine (ODA) bonded Fc (Fc-C18) as the delivery system. HA-Fc reserved the ability of HA to target the CD44 receptor of the tumor cell surface, and the dual-Fc region provided a rigid space for securely binding ICG through metal-ligand interaction and π-π conjugation, ensuring excellent photostability. Additionally, the alkyl chain provided flexible confinement for the remaining ICG through hydrophobic forces, preserving its FL. Thereby, a balance is achieved between outstanding photostability and FL imaging capability. In vitro studies showed improved photobleaching resistance, enhanced FL stability, and increased singlet oxygen (1O2) production efficiency in ICG@HFFC. Further in vivo results display that ICG@HFFC had good tumor tracing ability and significant tumor inhibition which also exhibited good biocompatibility.. Therefore, ICG@HFFC provides an encouraging strategy to realize simultaneous enhanced tumor tracing and photothermal/photodynamic therapy (PTT/PDT) and offers a novel approach to address the limitations of ACQ dyes.
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Compuestos Ferrosos , Ácido Hialurónico , Verde de Indocianina , Metalocenos , Fotoquimioterapia , Compuestos Ferrosos/química , Humanos , Metalocenos/química , Animales , Ratones , Verde de Indocianina/química , Verde de Indocianina/uso terapéutico , Verde de Indocianina/farmacología , Ácido Hialurónico/química , Terapia Fototérmica , Femenino , Colorantes Fluorescentes/química , Colorantes Fluorescentes/farmacología , Ratones Endogámicos BALB C , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Ratones Desnudos , Línea Celular Tumoral , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Neoplasias/patología , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Nanopartículas/química , Nanopartículas/uso terapéuticoRESUMEN
Acute methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is a common and serious lung infection with high morbidity and mortality rates. Due to the increasing antibiotic resistance, toxicity, and pathogenicity of MRSA, there is an urgent need to explore effective antibacterial strategies. In this study, we developed a dry powder inhalable formulation which is composed of porous microspheres prepared from poly(lactic-co-glycolic acid) (PLGA), internally loaded with indocyanine green (ICG)-modified, heat-resistant phages that we screened for their high efficacy against MRSA. This formulation can deliver therapeutic doses of ICG-modified active phages to the deep lung tissue infection sites, avoiding rapid clearance by alveolar macrophages. Combined with the synergistic treatment of phage therapy and photothermal therapy, the formulation demonstrates potent bactericidal effects in acute MRSA pneumonia. With its long-term stability at room temperature and inhalable characteristics, this formulation has the potential to be a promising drug for the clinical treatment of MRSA pneumonia.
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Staphylococcus aureus Resistente a Meticilina , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Animales , Ratones , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Microesferas , Terapia Fototérmica , Neumonía Estafilocócica/terapia , Terapia de Fagos/métodos , Verde de Indocianina/química , Verde de Indocianina/farmacología , Verde de Indocianina/uso terapéutico , Verde de Indocianina/administración & dosificación , Antibacterianos/química , Antibacterianos/farmacología , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Administración por Inhalación , Humanos , Bacteriófagos/químicaRESUMEN
Purpose: Skin injury, often caused by physical or medical mishaps, presents a significant challenge as wound healing is critical to restore skin integrity and tissue function. However, external factors such as infection and inflammation can hinder wound healing, highlighting the importance of developing biomaterials with antibiotic and wound healing properties to treat infections and inflammation. In this study, a novel photothermal nanomaterial (MMPI) was synthesized for infected wound healing by loading indocyanine green (ICG) on magnesium-incorporated mesoporous bioactive glass (Mg-MBG) and coating its surface with polydopamine (PDA). Results: In this study, Mg-MBG and MMPI was synthesized via the sol-gel method and characterized it using various techniques such as scanning electron microscopy (SEM), the energy dispersive X-ray spectrometry (EDS) system and X-ray diffraction (XRD). The cytocompatibility of MMPI was evaluated by confocal laser scanning microscopy (CLSM), CCK8 assay, live/dead staining and F-actin staining of the cytoskeleton. The antibacterial efficiency was assessed using bacterial dead-acting staining, spread plate method (SPM) and TEM. The impact of MMPI on macrophage polarization was initially evaluated through flow cytometry, qPCR and ELISA. Additionally, an in vivo experiment was performed on a mouse model with skin excision infected. Histological analysis and RNA-seq analysis were utilized to analyze the in vivo wound healing and immunomodulation effect. Conclusion: Collectively, the new photothermal and photodynamic nanomaterial (MMPI) can achieve low-temperature antibacterial activity while accelerating wound healing, holds broad application prospects.
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Antibacterianos , Verde de Indocianina , Indoles , Fotoquimioterapia , Terapia Fototérmica , Especies Reactivas de Oxígeno , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Animales , Ratones , Verde de Indocianina/química , Verde de Indocianina/farmacología , Fotoquimioterapia/métodos , Antibacterianos/farmacología , Antibacterianos/química , Terapia Fototérmica/métodos , Indoles/química , Indoles/farmacología , Especies Reactivas de Oxígeno/metabolismo , Polímeros/química , Polímeros/farmacología , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/fisiología , Células RAW 264.7 , Piel/efectos de los fármacos , Nanoestructuras/química , Rayos InfrarrojosRESUMEN
In this research, a novel MgSiO3 fiber membrane (MSFM) loaded with indocyanine green (ICG) and doxorubicin (DOX) was prepared. Because of MgSiO3's unique lamellar structure composed of a silicon-oxygen tetrahedron, magnesium ion (Mg2+) moves easily and can be further replaced with other cations. Therefore, because of the positively charged functional group of ICG, MSFM has a rather high drug loading for ICG. In addition, there is electrostatic attraction between DOX (a cationic drug) and ICG (an anionic drug). Hence, after loading ICG, more DOX can be adsorbed into MSFM because of electrostatic interaction. The ICG endows the MSFM outstanding photothermal therapy (PTT) performance, and DOX as a chemotherapeutic drug can restrain tumor growth. On the one hand, H+ exchanged with the positively charged DOX based on the MgSiO3 special lamellar structure. On the other hand, the thermal effect could break the electrostatic interaction between ICG and DOX. Based on the above two points, both tumor acidic microenvironment and photothermal effect can trigger DOX release. What's more, in vitro and in vivo antiosteosarcoma therapy evaluations displayed a superior synergetic PTT-chemotherapy anticancer treatment and excellent biocompatibility of DOX&ICG-MSFM. Finally, the MSFM was proven to greatly promote cell proliferation, differentiation, and bone regeneration performance in vitro and in vivo. Therefore, MSFM provides a creative perspective in the design of multifunctional scaffolds and shows promising applications in controlled drug delivery, antitumor performance, and osteogenesis.
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Regeneración Ósea , Doxorrubicina , Verde de Indocianina , Osteosarcoma , Doxorrubicina/química , Doxorrubicina/farmacología , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/patología , Regeneración Ósea/efectos de los fármacos , Animales , Humanos , Verde de Indocianina/química , Verde de Indocianina/farmacología , Ratones , Silicatos de Magnesio/química , Terapia Fototérmica , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/patología , Liberación de FármacosRESUMEN
OBJECTIVE: To examine the specific characteristics of ICG-angiography during various bariatric interventions. MATERIAL AND METHODS: The study included 329 patients, with 105 (32%) undergoing sleeve gastrectomy (LSG), 98 (30%) undergoing mini-gastricbypass (MGB), 126 (38%) undergoing Roux-en-Y gastric bypass (RGB). Intraoperative ICG angiography was perfomed on all patients at 'control points', the perfusion of the gastric stump was qualitatively and quantitatively assessed. RESULTS: Intraoperative ICG angiography shows that during LSG the angioarchitectonics in the area of the His angle are crucial. The presence of the posterior gastric artery of the gastric main type is a prognostically unfavorable risk factor for the development of ischemic complications. Therefore, to expand the gastric stump it is necessary to suture a 40Fr nasogastric tube and perform peritonization of the staple line. Statistical difference in blood supply at three points were found between and within the two groups of patients (Gis angle area, gastric body, pyloric region) with a p-value <0.001. During MGB, one of the important stages is applying the first (transverse) stapler cassette between the branches of the right and left gastric arteries. This maintains blood supply in anastomosis area, preventing immediate complications such as GEA failure, as well as long-term complications like atrophic gastritis, peptic ulcers, and GEA stenosis. CONCLUSION: ICG angiography is a useful method for intraoperative assessment of angioarchitecture and perfusion of the gastric stump during bariatric surgery. This helps prevent tissue ischemia and reduce the risk of early and late postoperative complications.
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Angiografía , Cirugía Bariátrica , Verde de Indocianina , Humanos , Masculino , Femenino , Adulto , Cirugía Bariátrica/métodos , Cirugía Bariátrica/efectos adversos , Persona de Mediana Edad , Angiografía/métodos , Verde de Indocianina/administración & dosificación , Verde de Indocianina/farmacología , Gastrectomía/métodos , Gastrectomía/efectos adversos , Obesidad Mórbida/cirugía , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Estómago/irrigación sanguínea , Estómago/cirugía , Estómago/diagnóstico por imagen , Artería Gástrica/cirugía , Monitoreo Intraoperatorio/métodosRESUMEN
BACKGROUND: This study aimed to evaluate the impact of photodynamic therapy (PDT) using two photosensitizers, methylene blue and indocyanine green, on the microtensile bond strength of a universal adhesive to caries-affected dentin. METHODS: The occlusal enamel of 60 third molars was cut to expose the inner one-third of the dentin. Artificial caries were induced through a pH cycling process. The samples were divided into three groups: M (Methylene blue+ diode laser), I (Indocyanine green agents+ diode laser irradiation), and control. Each group was further divided into two subgroups according to the adhesive protocol (self-etch, total-etch). After restoring with Gradia composite resin, teeth were sectioned and exposed to 5000 thermal cycles. Microtensile bond strength was measured using a universal testing machine. The data were subjected to two- and one-way ANOVA and paired comparisons were performed by the Tamhane and Tukey tests. RESULTS: The study found significant effects of the photosensitizer, etching pattern, and their interactions on the microtensile bond strength of composite resin to caries-affected dentin (P < 0.001). In the self-etching mode, PDT with indocyanine green exhibited significantly higher bond strength values compared to PDT with methylene blue (P = 0.001) and the control groups (P < 0.001). However, no significant differences were observed in the total-etch mode. (P = 0.54). CONCLUSIONS: The etching mode played a more significant role in the bond strength when using the universal adhesive alongside PDT with methylene blue and indocyanine green. Employing two photosensitizers in PDT during the self-etch mode significantly increased the bond strength values.
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Dentina , Verde de Indocianina , Azul de Metileno , Fotoquimioterapia , Fármacos Fotosensibilizantes , Resistencia a la Tracción , Fármacos Fotosensibilizantes/farmacología , Fotoquimioterapia/métodos , Verde de Indocianina/farmacología , Azul de Metileno/farmacología , Humanos , Dentina/efectos de los fármacos , Caries Dental/tratamiento farmacológico , Caries Dental/terapia , Recubrimiento Dental Adhesivo/métodos , Láseres de Semiconductores/uso terapéutico , Resinas Compuestas/química , Cementos Dentales/farmacologíaRESUMEN
Purpose: Owing to its noninvasive nature, broad-spectrum effectiveness, minimal bacterial resistance, and high efficiency, phototherapy has significant potential for antibiotic-free antibacterial interventions and combating antibacterial biofilms. However, finding effective strategies to mitigate the detrimental effects of excessive temperature and elevated concentrations of reactive oxygen species (ROS) remains a pressing issue that requires immediate attention. Methods: In this study, we designed a pH-responsive cationic polymer sodium nitroside dihydrate/branched polyethylenimine-indocyanine green@polyethylene glycol (SNP/PEI-ICG@PEG) nanoplatform using the electrostatic adsorption method and Schiff's base reaction. Relevant testing techniques were applied to characterize and analyze SNP/PEI-ICG@PEG, proving the successful synthesis of the nanomaterials. In vivo and in vitro experiments were performed to evaluate the antimicrobial properties of SNP/PEI-ICG@PEG. Results: The morphology and particle size of SNP/PEI-ICG@PEG were observed via TEM. The zeta potential and UV-visible (UV-vis) results indicated the synthesis of the nanomaterials. The negligible cytotoxicity of up to 1 mg/mL of SNP/PEI-ICG@PEG in the presence or absence of light demonstrated its biosafety. Systematic in vivo and in vitro antimicrobial assays confirmed that SNP/PEI-ICG@PEG had good water solubility and biosafety and could be activated by near-infrared (NIR) light and synergistically treated using four therapeutic modes, photodynamic therapy (PDT), gaseous therapy (GT), mild photothermal therapy (PTT, 46 °C), and cation. Ultimately, the development of Gram-positive (G+) Staphylococcus aureus (S. aureus) and Gram-negative (G-) Escherichia coli (E. coli) were both completely killed in the free state, and the biofilm that had formed was eliminated. Conclusion: SNP/PEI-ICG@PEG demonstrated remarkable efficacy in achieving controlled multimodal synergistic antibacterial activity and biofilm infection treatment. The nanoplatform thus holds promise for future clinical applications.