RESUMEN
The combination of photothermal therapy (PTT) and photodynamic therapy (PDT) has emerged as a promising strategy for cancer treatment. However, the poor photostability and photothermal conversion efficiency (PCE) of organic small-molecule photosensitizers, and the intracellular glutathione (GSH)-mediated singlet oxygen scavenging largely decline the antitumor efficacy of PTT and PDT. Herein, a versatile nanophotosensitizer (NPS) system is developed by ingenious incorporation of indocyanine green (ICG) into the PEGylated chitosan (PEG-CS)-coated polydopamine (PDA) nanoparticles via multiple π-π stacking, hydrophobic and electrostatic interactions. The PEG-CS-covered NPS showed prominent colloidal and photothermal stability as well as high PCE (ca 62.8 %). Meanwhile, the Michael addition between NPS and GSH can consume GSH, thus reducing the GSH-induced singlet oxygen scavenging. After being internalized by CT26 cells, the NPS under near-infrared laser irradiation produced massive singlet oxygen with the aid of thermo-enhanced intracellular GSH depletion to elicit mitochondrial damage and lipid peroxide formation, thus leading to ferroptosis and apoptosis. Importantly, the combined PTT and PDT delivered by NPS effectively inhibited CT26 tumor growth in vivo by light-activated intense hyperthermia and redox homeostasis disturbance. Overall, this work presents a new tactic of boosting antitumor potency of ICG-mediated phototherapy by PEG-CS-covered NPS.
Asunto(s)
Quitosano , Glutatión , Nanopartículas , Fotoquimioterapia , Fármacos Fotosensibilizantes , Terapia Fototérmica , Polietilenglicoles , Quitosano/química , Fotoquimioterapia/métodos , Animales , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Glutatión/metabolismo , Polietilenglicoles/química , Ratones , Nanopartículas/química , Terapia Fototérmica/métodos , Línea Celular Tumoral , Verde de Indocianina/química , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Oxígeno Singlete/metabolismo , Humanos , Apoptosis/efectos de los fármacos , Indoles/química , Indoles/farmacología , Polímeros/químicaRESUMEN
The therapy of solid tumors is often hindered by the compact and rigid tumoral extracellular matrix (TECM). Precise reduction of TECM by hyaluronidase (HAase) in combination with nanotechnology is promising for solid tumor therapeutics, yet remains an enormous challenge. Inspired by the treatment of iron poisoning, here a remotely unwrapping strategy is proposed of metal-polyphenol-packaged HAase (named PPFH) by sequentially injecting PPFH and a clinically used iron-chelator deferoxamine (DFO). The in situ dynamic disassembly of PPFH can be triggered by the intravenously injected DFO, resulting in the release, reactivation, and deep penetration of encapsulated HAase inside tumors. Such a cost-effective HAase delivery strategy memorably improves the subsequent photothermal and photodynamic therapy (PTT/PDT)-induced intratumoral infiltration of cytotoxic T lymphocyte cells and the cross-talk between tumor and tumor-draining lymph nodes (TDLN), thereby decreasing the immunosuppression and optimizing tumoricidal immune response that can efficiently protect mice from tumor growth, metastasis, and recurrence in multiple mouse cancer models. Overall, this work presents a proof-of-concept of the dynamic disassembly of metal-polyphenol nanoparticles for extracellular drug delivery as well as the modulation of TECM and immunosuppressive tumor microenvironment.
Asunto(s)
Hialuronoglucosaminidasa , Fotoquimioterapia , Polifenoles , Animales , Hialuronoglucosaminidasa/metabolismo , Ratones , Polifenoles/química , Polifenoles/farmacología , Línea Celular Tumoral , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Neoplasias/patología , Humanos , Terapia Fototérmica , Nanopartículas/química , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Metales/químicaRESUMEN
Multifunctional phototheranostics, employing precise and non-invasive techniques, is widely developed to enhance theranostic efficiency of breast cancer (BC), reduce side-effects, and improve quality of life. Integrating all phototheranostic modalities into a single photosensitizer for highly effective BC treatment is particularly challenging due to the potential inefficiency and time consumption associated with repeated switching of multiple-wavelength lasers. Herein, a novel single NIR-II laser-triggered three-in-one nanosystem(PdCu NY) is rationally designed, which enables dual-modal (NIR-II FL/NIR-II PA) imaging-guided self-enhancing photothermal-photodynamic therapy (PTT-PDT) in NIR-II window. The PdCu NY based on optimal Pd/Cu molar-ratio(1:11) can be easily fabricated and large-scale production for simultaneous PTT-PDT against BC under a single 1064nm laser irradiation. Significantly, the PdCu NY acted as a promising photocatalyst for decomposition of H2O into O2 upon the same laser irradiation. In addition, the inherent catalase (CAT)-like activity of PdCu NYs enables photo-enzyme dual-catalytic O2 supply to effectively alleviate hypoxia, achieving self-enhanced PDT efficiency. These PTT-PDT self-enhanced nanosystems demonstrate precise lesion localization and complete tumor ablation using a single 1064nm laser source by "one-laser, multi-functions" strategy. More importantly, this study not only reports a three-in-one PdCu-based phototheranostic agent, but also sheds light on the exploration of versatile biosafety nanosystems for clinical applications.
Asunto(s)
Neoplasias de la Mama , Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Femenino , Fotoquimioterapia/métodos , Neoplasias de la Mama/tratamiento farmacológico , Calidad de Vida , Fármacos Fotosensibilizantes/uso terapéutico , Rayos Láser , Nanomedicina Teranóstica/métodos , Fototerapia , Neoplasias/tratamiento farmacológico , Línea Celular TumoralRESUMEN
Phototherapy is an effective strategy to control Candida albicans (C. albicans) infection without raising the concern of drug resistance. Despite its effectiveness, a higher dose of phototherapeutic power is required for C. albicans elimination compared to bacteria that have to be used, which is readily accompanied by off-target heat and toxic singlet oxygen to damage normal cells, thus limiting its usefulness for antifungal applications. Here to overcome this, we develop a "three-in-one" biomimetic nanoplatform consisting of an oxygen-dissolved perfluorocarbon camouflaged by a photosensitizer-loaded vaginal epithelial cell membrane. With a cell membrane coating, the nanoplatform is capable of specifically binding with C. albicans at the superficial or deep vaginal epithelium, thereby centering the phototherapeutic agents on C. albicans. Meanwhile, the cell membrane coating endows the nanoplatform to competitively protect healthy cells from candidalysin-medicated cytotoxicity. Upon candidalysin sequestration, pore-forming on the surface of the nanoplatform accelerates release of the preloaded photosensitizer and oxygen, resulting in enhanced phototherapeutic power for improved anti-C. albicans efficacy under near-infrared irradiation. In an intravaginal C. albicans-infected murine model, treatment with the nanoplatform leads to a significantly decreased C. albicans burden, particularly when leveraging candidalysin for further elevated phototherapy and C. albicans inhibition. Also, the same trends hold true when using the nanoplatform to treat the clinical C. albicans isolates. Overall, this biomimetic nanoplatform can target and bind with C. albicans and simultaneously neutralize the candidalysin and then transform such toxins that are always considered a positive part in driving C. albicans infection with the power of enhancing phototherapy for improved anti-C. albicans efficacy.
Asunto(s)
Candida albicans , Candidiasis Vulvovaginal , Células Epiteliales , Humanos , Animales , Ratones , Células Cultivadas , Candidiasis Vulvovaginal/terapia , Fototerapia , Fármacos Fotosensibilizantes/farmacologíaRESUMEN
Photothermal/photodynamic therapies (PTT/PDT) are multimodal approaches employing near-infrared (NIR) light-responsive photosensitizers for cancer treatment. In the current study, IR-775, a hydrophobic photosensitizer, was used in combination with a polyphenols (p)-rich ethyl acetate extract from Terminalia chebula to treat cancer. IR-775 dye and polyphenols were encapsulated in a poly(lactic acid) polymeric nanosystem (PpIR NPs) to increase the cell bioavailability. The hydrodynamic diameter of PpIR NPs is 142.6 ± 2 nm and exhibited physical stability. The nanosystem showed enhanced cellular uptake in a lung cancer cell line (A549). Cell cytotoxicity results indicate that PpIR NPs showed more than 82.46 ± 3% cell death upon NIR light treatment compared to the control groups. Both PDT and PTT generate reactive oxygen species (ROS) and cause hyperthermia, thereby enhancing cancer cell death. Qualitative and quantitative analyses have depicted that PpIR NPs with NIR light irradiation have decreased protein expression of HSP70 and PARP, and increased γ-H2AX, which collectively lead to cell death. After NIR light irradiation, the relative gene expression patterns of HSP70 and CDK2Na were also downregulated. Further, PpIR NPs uptake has been studied in 3D cells and in ovo bioimaging in zebrafish models. In conclusion, the PpIR NPs show good cancer cell cytotoxicity and present a potential nanosystem for bioimaging.
Asunto(s)
Hipertermia Inducida , Nanopartículas , Neoplasias , Fotoquimioterapia , Terminalia , Animales , Polifenoles/uso terapéutico , Fotoquimioterapia/métodos , Terapia Fototérmica , Hipertermia Inducida/métodos , Pez Cebra , Nanopartículas/uso terapéutico , Fármacos Fotosensibilizantes/farmacología , Neoplasias/tratamiento farmacológicoRESUMEN
To fight the flourishment of drug-resistant bacteria caused by antibiotics and the dissemination of antibiotic resistance genes (ARGs), it is of great urgency to develop multifunctional non-antibiotic agents with residual antibiotics elimination, and ARGs dissemination inhibition properties. Herein, sodium dodecyl sulfate (SDS) was modified onto the surface of Fe2O3 @MoS2 by ultrasonic method to obtain the Z-scheme, multifunctional Fe2O3 @MoS2 @SDS nanocomposites. The Fe2O3 @MoS2 @SDS (weight ratio of Fe2O3 @MoS2 and SDS was 1:1) was selected as the optimal agent. Under NIR irradiation, the Fe2O3 @MoS2 @SDS had a photothermal conversion efficiency of 45.96%, and could generate plenty of reactive oxygen species (ROS) at the same time. Under the synergy of photothermal and photodynamic, the antibacterial efficiency of Fe2O3 @MoS2 @SDS to E. coli, MRSA and P. aeruginosa could reach 99.95%, 99.97% and 99.58%, respectively, indicating excellent photothermal-photodynamic therapy (PPT) effect. The Fe2O3 @MoS2 @SDS also displayed photocatalytic activity in degradation of tetracycline (TC). The degradation rate of TC could reach 92.3% after 2 h of visible light irradiation. The obtained results indicated that a promising Fe2O3 @MoS2 @SDS composite based multifunctional nanoplatform could be constructed for NIR induced bacterial inactivation, antibiotics degradation and ARGs dissemination inhibition.
RESUMEN
An effective therapeutic strategy against methicillin-resistant Staphylococcus aureus (MRSA) that does not promote further drug resistance is highly desirable. While phototherapies have demonstrated considerable promise, their application toward bacterial infections can be limited by negative off-target effects to healthy cells. Here, a smart targeted nanoformulation consisting of a liquid perfluorocarbon core stabilized by a lipid membrane coating is developed. Using vancomycin as a targeting agent, the platform is capable of specifically delivering an encapsulated photosensitizer along with oxygen to sites of MRSA infection, where high concentrations of pore-forming toxins trigger on-demand payload release. Upon subsequent near-infrared irradiation, local increases in temperature and reactive oxygen species effectively kill the bacteria. Additionally, the secreted toxins that are captured by the nanoformulation can be processed by resident immune cells to promote multiantigenic immunity that protects against secondary MRSA infections. Overall, the reported approach for the on-demand release of phototherapeutic agents into sites of infection could be applied against a wide range of high-priority pathogens.
Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Humanos , Liposomas/farmacología , Pruebas de Sensibilidad Microbiana , Fototerapia , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/prevención & controlRESUMEN
In order to overcome the limitation of traditional therapies for cancer and improve the accuracy of treatment, more advantageous cancer treatment methods need to be explored and studied. As a result, photothermal photodynamic therapy of breast cancer using bovine serum albumin (BSA) modifies molybdenum disulfide nanoflakes. Then the well-dispersed BSA-MoS2 NFs are loaded in the injectable and self-healing polysaccharide hydrogel which is prepared by the reaction of oxidized sodium alginate (OSA) and hydroxypropyl chitosan (HPCS) through the formation of Schiff base bonds. The injection and self-healing properties of the nanocomposite hydrogel are investigated. In vitro photothermal and photodynamic investigations demonstrate that BSA-MoS2 NFs possess obvious photothermal conversion and production of reactive oxygen species (ROS) under the irradiation of near infrared (NIR) laser (808 nm). In vivo anticancer investigation indicates that the nanocomposite hydrogel can be directly injected and remain in the tumor sites and achieve the synergistic photothermal-photodynamic therapy of cancer.
Asunto(s)
Neoplasias , Fotoquimioterapia , Disulfuros , Humanos , Hidrogeles/química , Hidrogeles/farmacología , Molibdeno/química , Molibdeno/farmacología , Nanogeles , Fototerapia/métodos , Polisacáridos/farmacología , Albúmina Sérica Bovina/químicaRESUMEN
A critical factor in developing an efficient photosensitizer-gold nanoparticle (PS-AuNP) hybrid system with improved plasmonic photosensitization is to allocate a suitable space between AuNPs and PS. Poly(amidoamine) (PAMAM) dendrimer is selected as a spacer between the PS and confeito-like gold nanoparticles (confeito-AuNPs), providing the required distance (≈2.5-22.5 nm) for plasmon-enhanced singlet oxygen generation and heat production upon 638-nm laser irradiation and increase the cellular internalization of the nanoconjugates. The loading of the PS, tetrakis(4-carboxyphenyl) porphyrin (TCPP), and modified zinc phthalocyanine (ZnPc1) onto PAMAM-confeito-AuNPs demonstrate better in vitro cancer cell-killing efficacy, as the combined photothermal-photodynamic therapies (PTT-PDTs) outperforms the single treatment modalities (PTT or PDT alone). These PS-PAMAM-confeito-AuNPs also demonstrate higher phototoxicity than photosensitizers directly conjugated to confeito-AuNPs (TCPP-confeito-AuNPs and ZnPc1-confeito-AuNPs) against all breast cancer cell lines tested (MDA-MB-231, MCF7, and 4T1). In the in vivo studies, TCPP-PAMAM-confeito-AuNPs are biocompatible and exhibit a selective tumor accumulation effect, resulting in higher antitumor efficacy than free TCPP, PAMAM-confeito-AuNPs, and TCPP-confeito-AuNPs. In vitro and in vivo evaluations confirm PAMAM effectiveness in facilitating cellular uptake, plasmon-enhanced singlet oxygen and heat generation. In summary, this study highlights the potential of integrating a PAMAM spacer in enhancing the plasmon effect-based photothermal-photodynamic anticancer treatment efficiency of PS-decorated confeito-AuNPs.
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Dendrímeros , Nanopartículas del Metal , Nanopartículas , Neoplasias , Fotoquimioterapia , Dendrímeros/farmacología , Oro/farmacología , Neoplasias/tratamiento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Oxígeno Singlete/metabolismoRESUMEN
Theranostic nanoplatforms with accurate diagnosis and effective therapy show a bright prospect for tumor treatments. Herein, a novel boracic acid-modified graphite carbon nitride and Prussian blue nanohybrid (PB@B-g-C3N4) was developed, which provides sialic acid-targeted Raman recognition and synergistic photothermal/photodynamic therapy in the near-infrared region. Owing to the specific interaction between boracic acid and sialic acid and Raman response at 2157 cm-1 of PB, the nanohybrids exhibit high specificity and Raman sensitivity for detection of the overexpressed sialic acid on tumor cells. Moreover, the photothermal conversion efficiency of PB@B-g-C3N4 is as high as 47.0% with 808 nm laser irradiation due to the enhanced absorbance of PB@B-g-C3N4. PB@B-g-C3N4 also possesses excellent photodynamic activity, which is attributed to the energy transfer of PB (type I) and electron transfer between PB and B-g-C3N4 (type II). This nanotheranostic agent for Raman recognition of cancer markers and synergistic photothermal/photodynamic therapy holds great potential for the development of efficient theranostic nanoplatforms.
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Neoplasias , Fotoquimioterapia , Ferrocianuros , Humanos , Ácido N-Acetilneuramínico , Neoplasias/terapia , Fototerapia/métodosRESUMEN
Pyroptosis, a kind of programmed cell death involving inflammation, might be a powerful way to fight against tumors, for example, using immunotherapy. However, how to trigger pyroptosis in cancer cells is an important issue. Photothermal (PTT)/photodynamic (PDT) therapy is a crucial strategy for inducing cancer cell pyroptosis with noninvasiveness. In this work, a sericin derivative modified with poly(γ-benzyl-l-glutamate) (PBLG) could self-assemble and was stable in an aqueous environment. Furthermore, the sericin derivative was conjugated with the tumor-targeting agent VB12 and loaded with IR780. Finally, we successfully synthesized VB12-sericin-PBLG-IR780 nanomicelles. The as-designed nanomicelles showed appropriate particle sizes, spherical morphology, improved photothermal stability, and high photothermal conversion efficiency (â¼40%), which generated reactive oxygen species (ROS) simultaneously. Through enhanced cellular uptake, VB12-sericin-PBLG-IR780 could deliver more IR780 into cancer cells. With near-infrared (NIR), the VB12-sericin-PBLG-IR780 could significantly inhibit the expression of ATP synthase, called ATP5MC3, followed by mitochondrial damage. The presence of mitochondrial reactive oxygen species (mitoROS) led to oxidative damage of mitochondrial DNA (mitoDNA), which further activates NLRP3/Caspase-1/gasdermin D (GSDMD)-dependent pyroptosis and could promote dendritic cell (DC) maturation by pyroptosis. Furthermore, our data showed that VB12-sericin-PBLG-IR780 could achieve a brilliant antitumor effect and could activate DC maturation, initiate T-cell recruiting, and prime adaptive antitumor efficiency. Overall, our well-prepared nanomicelles might offer a tumor-targeted approach for programmed cell pyroptosis and inducing antitumor immunity via photothermal PTT/PDT effect-induced mitoDNA oxidative damage.
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Nanopartículas , Fotoquimioterapia , Sericinas , Línea Celular Tumoral , ADN Mitocondrial , Indoles/farmacología , Estrés Oxidativo , Piroptosis , Especies Reactivas de OxígenoRESUMEN
Infection caused by antibiotic-resistant bacteria is serious threat for public health, and calls for novel antibacterial agents with versatile functions. In particular, nanomaterial is one of promising candidates to fight the increasing antibiotic resistance crisis. Here, we synthesized distinct Fe3O4@MoS2@SDS nanocomposites by ultrasonication assisted SDS coating on the Fe3O4@MoS2. Photothermal investigation indicated that the Fe3O4@MoS2@SDS showed excellent and stable photothermal performance and could be a NIR-induced photothermal reagent. It also displayed superior disinfection ability of Escherichia coli (E. coli), Methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa (P. aeruginosa) and in vivo wound healing ability with the help of NIR irradiation. According to the results of electron paramagnetic resonance (EPR) and radical capture tests, plenty of superoxide, hydroxyl radicals, singlet oxygen and living cell reactive oxygen species can be observed under NIR irradiation. Besides, the synergistic effect Fe3O4@MoS2@SDS and NIR irradiation eradicated almost all the biofilms of MRSA, so this kind of function enhanced the disinfection ability of Fe3O4@MoS2@SDS under NIR irradiation. Furthermore, its inhibition effect on antibiotic resistance gene dissemination was also investigated. As expected, the Fe3O4@MoS2@SDS could efficiently and broadly block the horizontal transfer of antibiotic resistance genes which mediated by conjugative plasmids, and its blocking effect was better than that we have reported Fe3O4@MoS2. Overall, our findings revealed that the Fe3O4@MoS2@SDS could be a potential candidate for photothermal-photodynamic therapy and antibiotic resistance gene dissemination inhibition.
Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Nanocompuestos , Fotoquimioterapia , Antibacterianos/farmacología , Farmacorresistencia Microbiana , Escherichia coli/genética , Molibdeno/farmacologíaRESUMEN
Developing new nanoplatforms for dynamically and quantitatively visualizing drug accumulation and targeting within tumors is crucial for precision cancer theranostic. However, achieving efficient tumor therapy via synergistic photothermal/photodynamic therapy (PTT/PDT) using a single excitation light source, remains a challenge. In this work, we designed Gd-surface functionalized copper sulfide nanoparticles that were modified with folic acid (FA) (Cu1.96S-Gd@FA) to overcome the above limitations and promote PTT/PDT therapeutics. Here, Cu1.96S-Gd nanoparticles were synthesized via a coprecipitation method. All samples exhibited high longitudinal relaxivity (up to 12.9 mM-1 s-1) and strong photothermal conversion efficiency (50.6%). Furthermore, the Gd ions promoted electron-hole segregation, inducing the Cu1.96S-Gd nanoparticles to generate more reactive oxygen species (ROS) than pure Cu1.96S nanoparticles. The Cu1.96S-Gd@FA enabled the targeting of folate receptor (FR) and promoted cellular uptake, consequently enhancing oncotherapy efficacy. Compared to non-targeted Cu1.96S-Gd, a higher signal enhancement for magnetic resonance (MR) imaging in vivo by Cu1.96S-Gd@FA was recorded. Given photothermal ability, the nanoparticles also could be visualized in infrared (IR) imaging. Furthermore, the nanoparticles exhibited biodegradation behavior and achieved good drug elimination performance via renal clearance. Our strategy, integrating Cu1.96S-Gd@FA nanoparticles, MR/IR dual-modal imaging, and PTT/PDT into one nanoplatform, demonstrated great potential for anti-breast cancer therapy by effectively targeting FR overexpressed breast cancer cells.
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Neoplasias de la Mama , Nanopartículas , Fotoquimioterapia , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Femenino , Ácido Fólico/metabolismo , Humanos , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Fotoquimioterapia/métodos , Fototerapia , Medicina de PrecisiónRESUMEN
Extensive research over past few decades has highlighted the challenges of chemotherapy and prompted the need for multimodality therapy because chemotherapy alone cannot fully eradicate the tumor due to physiological barriers in its effective delivery and systemic side effects. It can be mitigated by adopting nanoparticles as more effective delivery method, but none of them completely prevents drug toxicities. Utilizing multiple therapeutic modes such as phototherapy that can act synergistically with chemotherapy in controlling tumor growth, while reducing the overall dosage, could become a preferred route for cancer management. Careful selection of nanoparticle system, which can simultaneously deliver both drug and photosensitizer, can significantly enhance the therapeutic outcome. Therefore, in this paper, we report development and potential of immune-compatible and long circulating nanoerythrosomes for enhancing the therapeutic potential of camptothecin and indocyanine green against murine cancer model. The RBCs membrane simultaneously loaded the nonpolar drug and amphiphilic photosensitizer in its lipid bilayer, which self-assembled to form stable nanoparticles. These nano constructs absorbed light in the near-infrared region and hence are suitable for targeting deep seated tissues. The dual chemo-phototherapy had great effect on cell viability and had therapeutic value.
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Hipertermia Inducida , Neoplasias , Animales , Verde de Indocianina/farmacología , Ratones , Neoplasias/tratamiento farmacológico , Fármacos Fotosensibilizantes/farmacología , FototerapiaRESUMEN
The success of cancer therapy is always accompanied by severe side effects due to the high amount of toxic antitumor drugs that off-target normal organs/tissues. Herein, we report the development of a trifunctional layered double hydroxide (LDH) nanosystem for combined photochemotherapy of skin cancer at very low therapeutic doses. This nanosystem (ICG/Cu-LDH@BSA-DOX) is composed of acid-responsive bovine serum albumin-doxorubicin prodrug (BSA-DOX) and indocyanine green (ICG)-intercalated Cu-doped LDH nanoparticle. ICG/Cu-LDH@BSA-DOX is able to release DOX in an acid-triggered manner, efficiently and simultaneously generates heating and reactive oxygen species (ROS) upon 808 nm laser irradiation, and synergistically induces apoptosis of skin cancer cells. In vivo therapeutic evaluations demonstrate that ICG/Cu-LDH@BSA-DOX nearly eradicated the tumor tissues upon one-course treatment using very low doses of therapeutic agents (0.175 mg/kg DOX, 0.5 mg/kg Cu, and 0.25 mg/kg ICG) upon very mild 808 nm laser irradiation (0.3 W/cm2 for 2 min). This work thus provides a novel strategy to design anticancer nanomedicine for efficient combination cancer treatment with minimal side effects in clinical applications.
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Antibióticos Antineoplásicos/farmacología , Doxorrubicina/farmacología , Hidróxidos/farmacología , Melanoma/terapia , Fotoquimioterapia , Neoplasias Cutáneas/terapia , Animales , Antibióticos Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cobre/química , Cobre/farmacología , Relación Dosis-Respuesta a Droga , Doxorrubicina/química , Ensayos de Selección de Medicamentos Antitumorales , Hidróxidos/química , Verde de Indocianina/química , Verde de Indocianina/farmacología , Rayos Láser , Melanoma/metabolismo , Melanoma/patología , Ratones , Estructura Molecular , Tamaño de la Partícula , Especies Reactivas de Oxígeno/metabolismo , Albúmina Sérica Bovina/química , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Propiedades de SuperficieRESUMEN
PURPOSE: P-glycoprotein (P-gp), which is highly expressed in liver cancer cells, is one of the obstacles for the treatment of cancer. In this study, we have prepared and characterized a kind of novel ICG&Cur@MoS2 (ICG and Cur represent indocyanine green and curcumin, respectively) nanoplatform, which can achieve photothermal-photodynamic therapy and inhibit the P-gp effectively and safely. METHODS: In this work, plenty of studies including drug release, acute toxicity, Western blot, real-time PCR, cell viability, therapeutic experiment in vivo, immunofluorescence and so on were conducted to test the antitumor potential of ICG&Cur@MoS2 and the inhibitory effect of curcumin on P-gp. RESULTS: The ICG&Cur@MoS2 NPs exhibit an excellent photothermal effect and relatively low toxicity. Cell viability in the ICG&Cur@MoS2 + NIR group was significantly lower than that in ICG@MoS2 + NIR group (75.3% vs 81.2%, 59.0% vs 64.4%, 20.3% vs 27.5%, and 15.4% vs 22.3%) at the concentration of ICG at 0.5, 5, 25, 50 µg/mL (P<0.05 at each concentration). Western blot, Q-PCR, and immunofluorescence assay indicate ICG&Cur@MoS2 NPs can inhibit the P-gp effectively and safely. In vivo, the tumors in the ICG@MoS2 + NIR group are significantly smaller than those in the MoS2 + NIR group (95.0 vs 420.9 mm3, p<0.05). CONCLUSION: In conclusion, we have successfully synthesized ICG&Cur@MoS2 nanoparticles which can not only achieve PTT-PDT but also inhibit P-gp effectively. Our findings indicate that the PTT-PDT exhibits great potential in the treatment of hepatocellular carcinoma. Meanwhile, ICG&Cur@MoS2 can effectively inhibit the expression of P-gp, which will enhance the PDT effect.
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Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/antagonistas & inhibidores , Curcumina/química , Curcumina/farmacología , Disulfuros/química , Verde de Indocianina/química , Verde de Indocianina/farmacología , Molibdeno/química , Fotoquimioterapia/métodos , Animales , Línea Celular Tumoral , Curcumina/uso terapéutico , Liberación de Fármacos , Humanos , Verde de Indocianina/uso terapéutico , Nanopartículas/químicaRESUMEN
As a photosensitizer with effective photothermal (PTT) and photodynamic (PDT) response, IR780 has been widely explored as promising cancer phototheranostic molecule. However, the systematic administration of IR780 usually suffers from poor water solubility and low photostability, so that it cannot be administrated by parenteral route. In this study, we design a tetrahedral DNA (Td)-based nanosystem to load IR780 (IR780@Td) via electrostatic interaction and π-π stacking. After encapsulation, the water solubility and photostability of IR780 have been greatly improved, and the IR780@Td shows an appropriate nanoformulated size (224 nm) to facilitate hyperthermia-mediated tumor targeting by EPR effect. The nanostructure of Td is proved to be crucial for the proper size and good stability of IR780@Td nanoformulation for in vivo application. The in vitro and ex vivo PTT/PDT efficiencies of IR780 are improved in IR780@Td group. In the tumor-bearing mice, the accumulation of IR780 in tumor site is significantly high in IR780@Td group. Under near-infrared laser irradiation, the intravenous administration of IR780@Td promotes the tumor imaging and enhances anti-tumor effect than IR780 treatment. In summary, the proposed strategy shows promising effect in facilitating intravenous injection of IR780 and enhancing the phototheranostic efficacy for cancer treatment.
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Hipertermia Inducida , Nanopartículas , Nanoestructuras , Neoplasias , Fotoquimioterapia , Animales , Línea Celular Tumoral , ADN , Indoles , Ratones , Neoplasias/tratamiento farmacológicoRESUMEN
BACKGROUND: Antimicrobial photothermal/photodynamic therapy (PTT/PDT) with indocyanine green (ICG) is an adjuvant therapeutic approach in the treatment of periodontitis. To explore whether PTT/PDT with ICG causes cell death by apoptosis in human gingival fibroblast (HGF) cells, BAX and BCL-2 genes expression as key events for apoptosis were evaluated in this study. MATERIALS AND METHODS: HGF cells were treated with: 1) different concentrations (500-2000 µg/mL) of ICG alone, 2) Diode laser irradiation alone with a fluency of 39.06 J/cm2; 3) PTT/PDT combined different concentrations (500-2000 µg/mL) of ICG with an 808 nm diode laser with a fluency of 39.06 J/cm2, and 4) controls (untreated cells). After that, BAX and BCL-2 messenger RNA levels were evaluated by real-time quantitative reverse transcription PCR. RESULTS: PTT/PDT with 500 µg/mL of ICG caused significant increases in the expression of the BAX gene, with an 8.5-fold increase, which was approximately 7- and 8.5-fold higher than PTT/PDT with ICG for 1500 and 2000 µg/mL of ICG, respectively, indicating induction of apoptosis in HGF cells. ICG (in different test concentrations), diode laser, and PTT/PDT with ICG (1500 and 2000 µg/mL of ICG) treatment displayed insignificant increases in expression levels of BAX (all p>0.05). Our experiments showed an insignificant increase (1.1-1.6-fold) in the expression of BCL-2 after ICG, diode laser, and PTT/PDT with ICG treatment (all p>0.05). CONCLUSIONS: This study suggests that various concentration of ICG can be the diverse expression of BAX responses to PTT/PDT on HGF cells.
Asunto(s)
Apoptosis/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Verde de Indocianina/farmacología , Periodontitis/terapia , Fotoquimioterapia , Fármacos Fotosensibilizantes/farmacología , Proteínas Proto-Oncogénicas c-bcl-2/efectos de los fármacos , Proteína X Asociada a bcl-2/efectos de los fármacos , Antiinfecciosos/farmacología , Apoptosis/genética , Apoptosis/efectos de la radiación , Células Cultivadas , Fibroblastos/metabolismo , Fibroblastos/efectos de la radiación , Humanos , Terapia Fototérmica , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/efectos de la radiación , ARN Mensajero/efectos de los fármacos , ARN Mensajero/efectos de la radiación , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/efectos de la radiaciónRESUMEN
The hypoxia of the tumor microenvironment (TME) often hinders the effectiveness of cancer treatments, especially O2-dependent photodynamic therapy (PDT). Methods: An integrated iridium oxide (IrO2)-manganese dioxide (MnO2) nanotheranostic agent was fabricated through bovine serum albumin (BSA)-based biomineralization of Ir3+ and Mn2+. BSA was first covalently modified with chlorin e6 (Ce6), and used to fabricate multifunctional BSA-Ce6@IrO2/MnO2 nanoparticles (NPs) for computed X-ray tomography (CT) and photoacoustic (PA) imaging-guided PDT and photothermal (PTT) therapy of cancer. Extensive in vitro and in vivo studies were performed. Results: The theranostic agent produced can relieve tumor hypoxia by the decomposition of endogenous H2O2 in cancer cells to oxygen. The oxygen generated can be exploited for improved PDT. Paramagnetic Mn2+ released from the NPs in the acidic TME permits magnetic resonance imaging (MRI) to be performed. The exceptional photothermal conversion efficiency (65.3%) and high X-ray absorption coefficient of IrO2 further endow the NPs with the ability to be used in computed CT and PA imaging. Extensive antitumor studies demonstrated that the BSA-Ce6@IrO2/MnO2 nanoplatform inhibits cancer cell growth, particularly after combined PTT and PDT. Systematic in vivo biosafety evaluations confirmed the high biocompatibility of the nanoplatform. Conclusion: This work not only provides a novel strategy for designing albumin-based nanohybrids for theranostic applications but also provides a facile approach for extending the biomedical applications of iridium-based materials.
Asunto(s)
Biomineralización , Peróxido de Hidrógeno/metabolismo , Imagen Multimodal/métodos , Neoplasias/terapia , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Nanomedicina Teranóstica/métodos , Animales , Línea Celular Tumoral , Terapia Combinada/métodos , Femenino , Humanos , Peróxido de Hidrógeno/química , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias/diagnóstico por imagen , Neoplasias/patología , Ratas , Ratas Sprague-Dawley , Distribución Tisular , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Although neodymium vanadate (NdVO4) has been investigated and applied in some fields owing to its intensive ultraviolet (UV) light absorption, weak absorption in visible (Vis) and near infrared (NIR) regions constrains its environmental remediation and biomedical applications. Herein, plasmonic precious metal Au as light trapping agent is deposited onto NdVO4 to form metal/semiconductor hybrid nanostructure for improving the Vis/NIR light absorption. NdVO4/Au heterojunction nanocrystals (NCs) were synthesized by NdVO4 nanorods (NRs) and plasmonic Au nanoparticles (NPs), followed by introducing polyvinylpyrrolidone (PVP) to enhance stability and biocompatibility, which exhibit elevated photocatalytic performance for organic dye degradation, photothermal conversion effect as high as 32.15% and cytotoxic reactive oxygen species (ROS) production ability. NdVO4/Au can be internalized efficiently via endocytosis and cause apparent phototoxicity on HeLa cells. In vivo experiments further show that NdVO4/Au can act as a high-efficiency NIR light-triggered anticancer agent with excellent tumor inhibition effect. In addition, based on outstanding light-to-heat conversion performance and thermal expansion effect under NIR irradiation, NdVO4/Au provides photothermal (PT) and photoacoustic (PA) dual-modal imaging platform for precise cancer diagnosis and treatment. STATEMENTS OF SIGNIFICANCE: It's the first report on integrating precious metal Au and rare earth orthovanadates semiconductor into NdVO4/Au heterojunction NCs. The as-prepared NdVO4/Au heterojunction NCs exhibits improved absorption in Vis/NIR region and increased generation efficiency of photo-induced electron/hole pairs due to the LSPR effect, which results in enhanced photothermal conversion efficiency and the production ability of cytotoxic O2- and OH in comparison with pristine NdVO4. For further clinical application, NdVO4/Au heterojunction NCs could be served as anticancer therapeutic agent for PA/PT dual-modal imaging guided and NIR-triggered photothermal/photodynamic synergistic anticancer treatment.