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1.
Adv Healthc Mater ; : e2401131, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39225395

RESUMEN

Bacterial infections can pose significant health risks as they have the potential to cause a range of illnesses. These infections can spread rapidly and lead to complications if not promptly diagnosed and treated. Therefore, it is of great significance to develop a probe to selectively target and image pathogenic bacteria while simultaneously killing them, as there are currently no effective clinical solutions available. This study presents a novel approach using near-infrared carbonized polymer dots (NIR-CPDs) for simultaneous in vivo imaging and treatment of bacterial infections. The core-shell structure of the NIR-CPDs facilitates their incorporation into bacterial cell membranes, leading to an increase in fluorescence brightness and photostability. Significantly, the NIR-CPDs exhibit selective bacterial-targeting properties, specifically identifying Staphylococcus aureus (S. aureus) while sparing Escherichia coli (E. coli). Moreover, under 808 nm laser irradiation, the NIR-CPDs exhibit potent photodynamic effects by generating reactive oxygen species that target and damage bacterial membranes. In vivo experiments on infected mouse models demonstrate not only precise imaging capabilities but also significant therapeutic efficacy, with marked improvements in wound healing. The study provides the dual-functional potential of NIR-CPDs as a highly effective tool for the advancement of medical diagnostics and therapeutics in the fight against bacterial infections.

2.
Theranostics ; 14(12): 4667-4682, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39239517

RESUMEN

Background: Effective innate immunity activation could dramatically improve the anti-tumor efficacy and increase the beneficiary population of immunotherapy. However, the anti-tumor effect of unimodal immunotherapy is still not satisfactory. Methods: Herein, a novel relay-type innate immunity activation strategy based on photo-immunotherapy mediated by a water-soluble aggregation-induced emission luminogen, PEG420-TQ, with the assistant of toll-like receptor 7 (TLR-7) agonist, imiquimod (R837), was developed and constructed. Results: The strategy could promote tumor cells to undergo immunogenic cell death (ICD) induced by the well-designed PEG420-TQ@R837 (PTQ@R) nanoplatform under light irradiation, which in turn enhanced the infiltration of immune cells and the activation of innate immune cells to achieve the first innate immunity activation. The second innate immunity activation was subsequently achieved by drug delivery of R837 via apoptotic bodies (ApoBDs), further enhancing the anti-tumor activity of infiltrated immune cells. Conclusion: The strategy ultimately demonstrated robust innate immunity activation and achieved excellent performance against tumor growth and metastasis. The construction of the relay-type innate immunity activation strategy could provide a new idea for the application of immunotherapy in clinical trials.


Asunto(s)
Imiquimod , Inmunidad Innata , Inmunoterapia , Inmunidad Innata/efectos de los fármacos , Animales , Inmunoterapia/métodos , Ratones , Imiquimod/uso terapéutico , Imiquimod/farmacología , Línea Celular Tumoral , Humanos , Neoplasias/inmunología , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Agua/química , Receptor Toll-Like 7/agonistas , Femenino , Fototerapia/métodos , Nanopartículas/química , Ratones Endogámicos BALB C , Muerte Celular Inmunogénica/efectos de los fármacos , Rayos Infrarrojos
3.
Colloids Surf B Biointerfaces ; 245: 114193, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39241635

RESUMEN

Pathological thrombus can cause serious acute diseases that present a significant threat to human health, such as myocardial infarction and stroke. Challenges remain in achieving effective thrombolysis and real-time monitoring of therapeutic effects while minimizing side effects. Herein,a multifunctional nanoplatform (TG-OPDEA@UK/MnO2-H1080) with enhanced thrombus-permeability was developed to monitor the therapeutic effect of antioxidant-thrombolysis by hydroxyl radical-responsive NIR-II fluorescence imaging. The polyzwitterion poly (oxidized N,N-Diethylaminoethyl methacrylate-co-n-butyl methacrylate) (OPDEA) was prepared as the matrix of nanoparticles to simultaneously loading urokinase (UK) and MnO2 QDs, as well as NIR-II fluorescent molecule, H-1080. Subsequently, the fibrin targeted peptide CREKA was modified on the surface of the nanoparticles. OPDEA exhibits efficient loading capacity while endowing nanoparticles with the ability to effectively increased penetration depth of UK by 94.1 % into the thrombus, for extensive thrombolysis and fluorescence monitoring. The loaded UK exhibited good thrombolytic effect and greatly reduced the risk of bleeding by 82.6 %. TG-OPDEA@UK/MnO2-H1080 showed good thrombolytic efficacy and specific thrombus monitoring in the mouse carotid artery thrombosis model induced by ferric chloride (FeCl3). This work prepares a nanoplatform for thrombolytic therapy and real-time efficacy assessment based on an independent externally forced thrombus penetration delivery strategy.

4.
Acta Biomater ; 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39243836

RESUMEN

Photodynamic therapy (PDT) has attracted widespread attention from researchers as an emerging cancer treatment method. There have been many reports on various types of NIR-II photosensitizers for imaging and treatment of tumor sites. However, there are few reports on the development of NIR-II organic small molecule photosensitizers that have intelligent response to the tumor microenvironment, precise imaging, real-time treatment, and high biocompatibility. In this work, we developed a series of NIR-II photosensitizers (RBTs) with near-infrared excitation, good photostability, and large Stokes shift. Among them, RBT-Br exhibited higher reactive oxygen species (ROS) generation efficiency due to the introduction of halogen heavy atoms to enhance intersystem crossing (ISC). It is noteworthy that RBT-Br can generate singlet oxygen (1O2) and superoxide anion radicals (•O2-) simultaneously under 730 nm laser. Subsequently, we used molecular engineering technology to construct three pH-responsive NIR-II photosensitizers (RBT-pHs) by utilizing the closure of the lactam ring, among which RBT-pH-1 (pKa = 6.78) is able to be directionally activated under the stimulation of tumor micro-acid environment, with its fluorescence emission window reaching 933 nm. Subsequently, RBT-pH-1 NPs encapsulated in DSPE-mPEG5k were applied for PDT treatment of mouse tumors. The results showed that RBT-pH-1 NPs were activated by the acidic tumor microenvironment and generated ROS under laser excitation, exhibiting precise tumor imaging and significant tumor growth inhibition. We look forward to these multifunctional NIR-II organic small molecule photosensitizers providing a more efficient approach for clinical treatment of tumors. STATEMENT OF SIGNIFICANCE: : A reversible pH-switchable NIR-II nano-photosensitizer RBT-pH-1 NPs (pKa = 6.76) is developed for precise imaging and PDT therapy of mouse tumors, which can be effectively used for targeted enrichment and activation of tumor micro-acid environments. The results show that this NIR-II photosensitizer generates ROS through tumor micro-acid environment stimulation and laser triggering, showing precise tumor imaging guidance and significant tumor growth inhibition.

5.
Angew Chem Int Ed Engl ; : e202416160, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39289151

RESUMEN

Tetracene and pentacene are large, promising building blocks for construction of complex molecular nanocarbons due to their extraordinary photophysical and electronic properties. Herein, two acene-integrated buckybowls, composed of two rows of tetracenes and pentacenes fused through s-indacene unit at the zigzag edges, have been synthesized and characterized. Compared to parent tetracene and pentacene, the buckybowls are extremely stable and show much smaller electrochemical band gaps. Kinetic studies gave the bowl-to-bowl inversion barriers of 11.7 and 13.3 kcal mol-1. Subsequent investigations on magnetic ring currents revealed two local diatropic currents at two rows of acenes and one paratropic current at the s-indacene unit, respectively. Notably, both buckybowls show a broad absorption that reaches into near-infrared II region, and a high photothermal conversion efficiency (> 90%) was achieved when exposed to near-infrared 1064 nm laser photo-irradiation. This study highlights the unusual nature of merging the intrinsic properties of acenes with the inherent properties of buckybowls and showcases a potential avenue for acene utilization for the design of novel complex nanocarbons with a broad range of applications.

6.
Chemistry ; : e202402566, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39145432

RESUMEN

As a post transcriptional regulator of gene expression, miRNA is closely related to many major human diseases, especially cancer. Therefore, its precise detection is very important for disease diagnosis and treatment. With the advancement of fluorescent dye and imaging technology, the focus has shifted from in vitro microRNAs (miRNA) detection to in vivo miRNA imaging. This concept review summarizes signal amplification strategies including DNAzyme catalytic reaction, hybrid chain reaction (HCR), catalytic hairpin assembly (CHA) to enhance detection signal of lowly expressed miRNAs; external stimuli of ultraviolet (UV) light or near-infrared region (NIR) light, and internal stimuli such as adenosine triphosphate (ATP), glutathione (GSH), protease and cell membrane protein to prevent nonspecific activation for the avoidance of false positive signal; and the development of fluorescent probes with emission in NIR for in vivo miRNA imaging; as well as rare earth nanoparticle based the second near-infrared window (NIR-II) nanoprobes with excellent tissue penetration and depth for in vivo miRNA imaging. The concept review also indicated current challenges for in vivo miRNA imaging including the dynamic monitoring of miRNA expression change and simultaneous in vivo imaging of multiple miRNAs.

7.
Adv Healthc Mater ; : e2401434, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39171782

RESUMEN

Despite significant efforts to eliminate bacterial biofilm within root canals, achieving effective disinfection remains challenging due to the complex anatomy and limitations of disinfectants. In this study, a second near-infrared (NIR-II) semiconducting polymer with aggregation-induced emission (AIE) properties, named PIDT-TBT, is deliberately designed and synthesized. This proposes an AIE luminogen-based sterilization strategy in synergy with a low concentration of sodium hypochlorite (NaClO). Water-dispersible PIDT-TBT nanoparticles (NPs) are prepared, demonstrating good biocompatibility, as well as photothermal and photodynamic properties. Subsequent antibacterial tests show that PIDT-TBT NPs exhibit excellent bactericidal effects against three bacterial strains: Staphylococcus aureus, Streptococcus mutans, and Enterococcus faecalis, upon 808 nm laser irradiation. In synergy with a low concentration of NaClO (0.5%) solution, PIDT-TBT NPs significantly improves the outcome of root canal treatment under 808 nm laser irradiation in a human extracted tooth root canal infection model. Additionally, it is found that PIDT-TBT NPs combine with a low concentration of NaClO solution could safely dissolve dentin debris and further increase the efficiency of root canal preparation by altering the elemental composition of the inner root canal wall.

8.
J Nanobiotechnology ; 22(1): 481, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39135072

RESUMEN

Photothermal therapy (PTT) for cancers guided by optical imaging has recently shown great potential for precise diagnosis and efficient therapy. The second near-infrared window (NIR-II, 1000-1700 nm) fluorescence imaging (FLI) is highly desirable owing to its good spatial and temporal resolution, deep tissue penetration, and negligible tissue toxicity. Organic small molecules are attractive as imaging and treatment agents in biomedical research because of their low toxicity, fast clearance rate, diverse structures, ease of modification, and excellent biocompatibility. Various organic small molecules have been investigated for biomedical applications. However, there are few reports on the use of croconaine dyes (CRs), especially NIR-II emission CRs. To our knowledge, there have been no prior reports of NIR-II emissive small organic photothermal agents (SOPTAs) based on CRs. Herein, we report a croconaine dye (CR-TPE-T)-based nanoparticle (CR NP) with absorption and fluorescence emission in the NIR-I and NIR-II windows, respectively. The CR NPs exhibited intense NIR absorption, outstanding photothermal properties, and good biological compatibility. In vivo studies showed that CR NPs not only achieved real-time, noninvasive NIR-II FLI of tumors, but also induced significant tumor ablation with laser irradiation guided by imaging, without apparent side effects, and promoted the formation of antitumor immune memory in a colorectal cancer model. In addition, the CR NPs displayed efficient inhibition of breast tumor growth, improved longevity of mice and triggered efficient systemic immune responses, which further inhibited tumor metastasis to the lungs. Our study demonstrates the great potential of CRs as therapeutic agents in the NIR-II region for cancer diagnosis.


Asunto(s)
Ratones Endogámicos BALB C , Nanopartículas , Imagen Óptica , Terapia Fototérmica , Animales , Terapia Fototérmica/métodos , Ratones , Femenino , Imagen Óptica/métodos , Línea Celular Tumoral , Nanopartículas/química , Nanopartículas/uso terapéutico , Humanos , Colorantes Fluorescentes/química , Rayos Infrarrojos , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/terapia
9.
J Nanobiotechnology ; 22(1): 478, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39135099

RESUMEN

PURPOSE OF REVIEW: Atherosclerosis, a highly pathogenic and lethal disease, is difficult to locate accurately via conventional imaging because of its scattered and deep lesions. However, second near-infrared (NIR-II) nanomaterials show great application potential in the tracing of atherosclerotic plaques due to their excellent penetration and angiographic capabilities. RECENT FINDINGS: With the development of nanotechnology, among many nanomaterials available for the visual diagnosis and treatment of cardiovascular diseases, optical nanomaterials provide strong support for various biomedical applications because of their advantages, such as noninvasive, nondestructive and molecular component imaging. Among optical nanomaterials of different wavelengths, NIR-II-range (900 ~ 1700 nm) nanomaterials have been gradually applied in the visual diagnosis and treatment of atherosclerosis and other vascular diseases because of their deep biological tissue penetration and limited background interference. This review explored in detail the prospects and challenges of the biological imaging and clinical application of NIR-II nanomaterials in treating atherosclerosis.


Asunto(s)
Aterosclerosis , Nanoestructuras , Aterosclerosis/diagnóstico por imagen , Humanos , Nanoestructuras/química , Animales , Rayos Infrarrojos , Placa Aterosclerótica/diagnóstico por imagen , Imagen Óptica/métodos , Espectroscopía Infrarroja Corta/métodos
10.
J Colloid Interface Sci ; 678(Pt A): 42-52, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39180847

RESUMEN

Photodynamic therapy (PDT) and catalytic therapy were promising treatment modes, but tumor hypoxia and poor catalytic activity severely limited their efficacies. Herein, using a porphyrin metal-organic framework (PCN-224) as nanocarrier, a platinum/palladium (Pt/Pd) dual-modified PCN-224 nanoprobe (PCN-224-Pt@Pd) with strong peroxidase (POD)/catalase (CAT)-like activities was developed, achieving photothermal-promoted PDT/catalytic therapy. Compared with single ultrasmall Pt modifying, CAT-like activity of Pt/Pd dual-modifying increased oxygen concentration from 6.24 to 9.35 mg/L, which improved singlet oxygen (1O2) yield from 63.8 % to 82.9 %. Moreover, POD-like activity of Pt/Pd dual-modifying significantly accelerated hydroxyl radicals (·OH) generation. Importantly, PCN-224-Pt@Pd possessed near-infrared II (NIR-II) photothermal effect with a high efficiency (55.6 %), which further promoted ·OH production. Under combined therapy of PCN-224-Pt@Pd, the cell survival rate greatly reduced to 5.8 %, and the tumors were cured, suggesting NIR-II photothermal-enhanced PDT/catalytic therapy.

11.
Angew Chem Int Ed Engl ; : e202414259, 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39185587

RESUMEN

Pathogenic infectious diseases have persistently posed significant threats to public health. Phototheranostics, which combines the functions of diagnostic imaging and therapy, presents an extremely promising solution to block the spread of pathogens as well as the outbreak of epidemics owing to its merits of a wide-spectrum of activity, high controllability, non-invasiveness, and difficult to acquire resistance. Among multifarious phototheranostic agents, second near-infrared (NIR-II, 1000-1700 nm) aggregation-induced emission luminogens (AIEgens) are notable by virtue of their deep penetration depth, excellent biocompatibility, balanced radiative and nonradiative decay and aggregation-enhanced theranostic performance, making them an ideal option for combating pathogens. This minireview provides a systematical summary of the latest advancements in NIR-II AIEgens with emphasis on the molecular design and nanoplatform formulation to fulfill high-efficiency in treating bacterial and viral pathogens, classified by disease models. Then, the current challenges, potential opportunities, and future research directions are presented to facilitate the further progress of this emerging field.

12.
Adv Mater ; : e2407927, 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39185788

RESUMEN

The combination of nanoparticles and tumor-targeting bacteria for cancer immunotherapy can overcome the shortcomings of poor nanoparticle accumulation, limited penetration, and restricted distribution. However, it remains a great challenge for the hybrid system to improve therapeutic efficacy through the simultaneous and controllable regulation of immune cells and tumor cells. Herein, a hybrid therapeutic platform is rationally designed to achieve immune cascade-augmented cancer immunotherapy. To construct the hybrids, photothermal nanoparticles responsive to light in the second near-infrared (NIR-II) region are conjugated onto the surface of engineered bacteria through pH-responsive Schiff base bonds. Taking advantage of the hypoxia targeting and deep penetration characteristics of the bacteria, the hybrids can accumulate at tumor sites. Then nanoparticles detach from the bacteria to realize genetic engineering of tumor cells, which induces tumor cell apoptosis and down-regulate the expression of programmed cell death ligand 1 to alleviate immunosuppressive tumor microenvironment. The mild photothermal heating can not only induce tumor-associated antigen release, but also trigger sustainable expression of cytokine interleukin-2. Notably, a synergistic antitumor effect is achieved between the process of p53 transfection and NIR-II light-activated genetic engineering of bacteria. This work proposes a facile strategy for the construction of hybrid system to achieve cascade-augmented cancer immunotherapy.

13.
ACS Nano ; 18(34): 23599-23614, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39141682

RESUMEN

Atherosclerosis (AS) is a chronic inflammatory disorder characterized by arterial intimal lipid plaques. Small interfering ribonucleic acid (siRNA)-based therapies, with their ability to suppress specific genes with high targeting precision and minimal side effects, have shown great potential for AS treatment. However, targets of siRNA therapies based on macrophages for AS treatment are still limited. Olfactory receptor 2 (Olfr2), a potential target for plaque formation, was discovered recently. Herein, anti-Olfr2 siRNA (si-Olfr2) targeting macrophages was designed, and the theranostic platform encapsulating si-Olfr2 to target macrophages within atherosclerotic lesions was also developed, with the aim of downregulating Olfr2, as well as diagnosing AS through photoacoustic imaging (PAI) in the second near-infrared (NIR-II) window with high resolution. By utilization of a reactive oxygen species (ROS)-responsive nanocarrier system, the expression of Olfr2 on macrophages within atherosclerotic plaques was effectively downregulated, leading to the inhibition of NLR family pyrin domain containing 3 (NLRP3) inflammasome activation and interleukin-1 ß (IL-1ß) secretion, thereby reducing the formation of atherosclerotic plaques. As manifested by decreased Olfr2 expression, the lesions exhibited a significantly alleviated inflammatory response that led to reduced lipid deposition, macrophage apoptosis, and a noticeable decrease in the necrotic areas. This study provides a proof of concept for evaluating the theranostic nanoplatform to specifically deliver si-Olfr2 to lesional macrophages for AS diagnosis and treatment.


Asunto(s)
Aterosclerosis , Nanopartículas , ARN Interferente Pequeño , Especies Reactivas de Oxígeno , Nanomedicina Teranóstica , Especies Reactivas de Oxígeno/metabolismo , Animales , Ratones , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Aterosclerosis/metabolismo , Aterosclerosis/terapia , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/genética , Aterosclerosis/patología , Nanopartículas/química , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Receptores Odorantes/antagonistas & inhibidores , Macrófagos/metabolismo , Células RAW 264.7 , Humanos , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Inflamasomas/metabolismo , Placa Aterosclerótica
14.
ACS Nano ; 18(33): 22153-22171, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39118372

RESUMEN

cGAS/STING pathway, which is highly related to tumor hypoxia, is considered as a potential target for remodeling the immunosuppressive microenvironment of solid tumors. Metal ions, such as Mn2+, activate the cGAS/STING pathway, but their efficacy in cancer therapy is limited by insufficient effect on immunogenic tumor cell death of a single ion. Here, we evaluate the association between tumor hypoxia and cGAS/STING inhibition and report a polymetallic-immunotherapy strategy based on large mesoporous trimetal-based nanozyme (AuPdRh) coordinated with Mn2+ (Mn2+@AuPdRh) to activate cGAS/STING signaling for robust adaptive antitumor immunity. Specifically, the inherent CAT-like activity of this polymetallic Mn2+@AuPdRh nanozyme decomposes the endogenous H2O2 into O2 to relieve tumor hypoxia induced suppression of cGAS/STING signaling. Moreover, the Mn2+@AuPdRh nanozyme displays a potent near-infrared-II photothermal effect and strong POD-mimic activity; and the generated hyperthermia and •OH radicals synergistically trigger immunogenic cell death in tumors, releasing abundant dsDNA, while the delivered Mn2+ augments the sensitivity of cGAS to dsDNA and activates the cGAS-STING pathway, thereby triggering downstream immunostimulatory signals to kill primary and distant metastatic tumors. Our study demonstrates the potential of metal-based nanozyme for STING-mediated tumor polymetallic-immunotherapy and may inspire the development of more effective strategies for cancer immunotherapy.


Asunto(s)
Inmunoterapia , Rayos Infrarrojos , Proteínas de la Membrana , Animales , Ratones , Proteínas de la Membrana/metabolismo , Manganeso/química , Manganeso/farmacología , Nucleotidiltransferasas/metabolismo , Porosidad , Transducción de Señal/efectos de los fármacos , Humanos , Hipoxia Tumoral/efectos de los fármacos , Oro/química , Oro/farmacología , Línea Celular Tumoral , Paladio/química , Paladio/farmacología , Antineoplásicos/farmacología , Antineoplásicos/química , Femenino
15.
Talanta ; 279: 126633, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39121551

RESUMEN

An innovative organic small molecule with a D-A structure was synthesized by connecting triphenylamine to BODIPY via a thiophene bridge. Triphenylamine and thiophene units ingeniously modulate the balance between steric hindrance and π-π interactions around the flat aza-BODIPY core. The molecule exhibits near-infrared fluorescence absorption and emits at roughly 1100 nm, featuring a significant Stokes shift. Both the molecule and its nanoparticles demonstrate high stability and achieve a remarkable 35 % photothermal conversion efficiency when conjugated with the P(OEGMA)20-P(Asp)14 copolymer. In vitro assessments show low dark toxicity and outstanding biocompatibility. Moreover, in vivo studies and photothermal therapy in mice indicate substantial tumor shrinkage and reduced recurrence, confirming its potential in cancer treatment. These results highlight the promise of this organic molecule and its nanoparticles for NIR-II imaging-guided photothermal therapy, introducing a novel approach to phototheranostic applications for cancer management.


Asunto(s)
Compuestos de Boro , Colorantes Fluorescentes , Rayos Infrarrojos , Nanopartículas , Péptidos , Nanopartículas/química , Compuestos de Boro/química , Animales , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Ratones , Humanos , Péptidos/química , Nanomedicina Teranóstica/métodos , Terapia Fototérmica , Ratones Endogámicos BALB C , Fototerapia
16.
Small ; : e2404007, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39140318

RESUMEN

Although research on photodynamic therapy (PDT) of malignant tumor has made considerable progress in recent years, it is a remaining challenge to extend PDT to the second near-infrared window (NIR-II) along with real-time and accurate NIR-II fluorescence imaging to determine drug enrichment status and achieve high treatment efficacy. In this work, lanthanide nanoparticles (Ln NPs)-based nanoplatform (LCR) equipped with photosensitizer Chlorin e6 (Ce6) and targeting molecular NH2-PEG1000-cRGDfK are developed, which can achieve NIR-II photodynamic therapy (PDT) and NIR-II fluorescence imaging by dual channel excitation. Under 808 nm excitation, Nd3+ in the outer layer can absorb the energy and transfer inward to emit strong NIR-II emissions (1064 and 1525 nm). Due to the low background noise of NIR-II light and the targeting effect of NH2-PEG1000-cRGDfK, LCR can recognize tiny tumor tissue (≈3 mm) and monitor drug distribution in vivo. Under 1530 nm excitation, internal Er3+ can be self-sensitized, generating intense upconversion emission (662 nm) that can effectively activate Ce6 for in vivo PDT due to the deep tissue penetration of NIR-II light. This study provides a paradigm of theranostic nanoplatform for both real-time fluorescence imaging and PDT of orthotopic breast tumor in NIR-II window.

17.
Adv Healthc Mater ; : e2402333, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39126238

RESUMEN

Numerous hemorrhagic disorders, particularly those presenting deep hemorrhage, pose diagnostic challenges, often leading to delayed treatment and severe outcomes. Near-infrared (NIR)-II fluorescence imaging offers advantages such as deep tissue penetration, real-time visualization, and a high signal-to-background ratio, making it highly suitable for diagnosing hemorrhagic diseases. In this study, an NIR-II fluorescent probe LJ-2P carrying carboxylic and phosphoric acid groups is successfully applied for imaging hemorrhagic diseases. LJ-2P demonstrates a strong affinity for fibrinogen and fibrin clots both computationally and experimentally, thus exhibiting increased brightness upon coagulation. As compared to Indocyanine Green, LJ-2P provides a longer imaging window, higher imaging specificity, and signal-to-background ratio, as well as superior photobleaching resistance in three disease models: gastric, pulmonary, and cerebral hemorrhages. These results reveal that LJ-2P demonstrates enhanced imaging capabilities, enabling precise identification of hemorrhagic sites.

18.
Small ; : e2402904, 2024 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-39128139

RESUMEN

Nanozyme catalytic therapy triggered by the tumor microenvironment (TME)-responsive enzyme-like catalytic activities is an emerging approach for tumor treatment. However, the poor catalytic efficiency of nanozymes in tumors and the toxic side effects on normal tissues limit their further development, primarily due to the limited uptake and penetration depth of nanozyme in tumor tissues. Here, a tumor-targeting TME and electric field stimuli-responsive nanozyme (AgPt@CaCO3-FA) is developed, which is capable of catalyzing the generation of ROS to induce cell death and releasing carbon monoxide (CO) specifically in tumor tissues for on-demand CO therapy and immunotherapy. Benefiting from the endogenous H2S activated NIR-II fluorescence (FL) imaging guidance, AgPt@CaCO3-FA can be delivered into the deeper site of tumor tissues resulted from the TME regulation via generated CO during the electrolysis process to improve the catalytic efficiency of nanozymes in tumors. Moreover, CO effectively relieve immunosuppression TME via reeducating tumor-supportive M2-like macrophages to tumoricidal M1-like macrophages and induce mitochondrial dysfunction by reducing mitochondrial membrane potential, triggering tumor cells apoptosis. The enzyme-like activities combined with CO therapy arouse distinct immunogenic cell death (ICD) effect. Therefore, AgPt@CaCO3-FA permits synergistic CO gas, catalytic therapy and immunotherapy, effectively eradicating orthotopic breast tumors and preventing tumor metastasis and recurrence.

19.
Mater Today Bio ; 28: 101166, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39189016

RESUMEN

Sentinel lymph node (SLN) biopsy is a commonly employed procedure for the routine assessment of axillary involvement in patients with breast cancer. Nevertheless, conventional SLN mapping cannot reliably distinguish the presence and absence of metastatic disease. Additionally, the complex anatomical structures and lymphatic drainage patterns surrounding tumor sites pose challenges to the sensitivity of the near-infrared fluorescence imaging with subcutaneously injected probes. To identifying the SLN metastases, we developed a novel nanoprobe for in vivo fluorescence imaging within the second near-infrared (NIR-II) range. This nanoprobe utilizes rare-earth nanoparticles (RENPs) to emit bright fluorescence at 1525 nm and is conjugated with tumor-targeted hyaluronic acid (HA) to facilitate the detection of metastatic SLN. Upon intravenous administration, RENPs@HA effectively migrated to SLNs and selectively entered metastatic breast tumor cells through CD44-mediated endocytosis. The RENPs@HA nanoprobes exhibited rapid accumulation in metastatic inguinal lymph nodes in mouse model, displaying a 5.8-fold-stronger fluorescence intensity to that observed in normal SLNs. Consequently, these nanoprobes effectively differentiate metastatic SLNs from normal SLNs. Importantly, the probes accurately detected micrometastases. These findings underscore the potential of RENPs@HA for real-time visualization and screening of SLNs metastasis.

20.
Adv Sci (Weinh) ; : e2302713, 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39206553

RESUMEN

As a new avenue for cancer research, phototheranostics has shown inexhaustible and vigorous vitality as it permits real-time diagnosis and concurrent in situ therapy upon non-invasive light-initiation. However, construction of an advanced material, allowing prominent phototheranostic outputs and synchronously surmounting the inherent deficiency of phototheranostics, would be an appealing yet significantly challenging task. Herein, an aggregation-induced emission (AIE)-active luminogen (namely DBD-TM) featured by intensive electron donor-acceptor strength and twisted architecture with finely modulated intramolecular motion, is tactfully designed and prepared. DBD-TM simultaneously possessed fluorescence emission in the second near-infrared (NIR-II) region and high-efficiency photothermal conversion. By integrating DBD-TM with anti-angiogenic agent sorafenib, a versatile nanomaterial is smoothly fabricated and utilized for trimodal imaging-navigated synergistic therapy involving photothermal therapy and anti-angiogenesis toward cancer. This advanced approach is capable of affording accurate tumor diagnosis, complete tumor elimination, and largely restrained tumor recurrence, evidently denoting a prominent theranostic formula beyond phototheranostics. This study will offer a blueprint for exploiting a new generation of cancer theranostics.

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