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1.
J Nanobiotechnology ; 22(1): 232, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720301

RESUMO

Diabetic wounds pose a challenge to healing due to increased bacterial susceptibility and poor vascularization. Effective healing requires simultaneous bacterial and biofilm elimination and angiogenesis stimulation. In this study, we incorporated polyaniline (PANI) and S-Nitrosoglutathione (GSNO) into a polyvinyl alcohol, chitosan, and hydroxypropyltrimethyl ammonium chloride chitosan (PVA/CS/HTCC) matrix, creating a versatile wound dressing membrane through electrospinning. The dressing combines the advantages of photothermal antibacterial therapy and nitric oxide gas therapy, exhibiting enduring and effective bactericidal activity and biofilm disruption against methicillin-sensitive Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, and Escherichia coli. Furthermore, the membrane's PTT effect and NO release exhibit significant synergistic activation, enabling a nanodetonator-like burst release of NO through NIR irradiation to disintegrate biofilms. Importantly, the nanofiber sustained a uniform release of nitric oxide, thereby catalyzing angiogenesis and advancing cellular migration. Ultimately, the employment of this membrane dressing culminated in the efficacious amelioration of diabetic-infected wounds in Sprague-Dawley rats, achieving wound closure within a concise duration of 14 days. Upon applying NIR irradiation to the PVA-CS-HTCC-PANI-GSNO nanofiber membrane, it swiftly eradicates bacteria and biofilm within 5 min, enhancing its inherent antibacterial and anti-biofilm properties through the powerful synergistic action of PTT and NO therapy. It also promotes angiogenesis, exhibits excellent biocompatibility, and is easy to use, highlighting its potential in treating diabetic wounds.


Assuntos
Antibacterianos , Bandagens , Biofilmes , Óxido Nítrico , Terapia Fototérmica , Ratos Sprague-Dawley , Cicatrização , Animais , Cicatrização/efeitos dos fármacos , Óxido Nítrico/farmacologia , Óxido Nítrico/metabolismo , Ratos , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/uso terapêutico , Biofilmes/efeitos dos fármacos , Terapia Fototérmica/métodos , Masculino , Quitosana/química , Quitosana/farmacologia , Nanofibras/química , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Diabetes Mellitus Experimental/complicações , Staphylococcus aureus/efeitos dos fármacos , Álcool de Polivinil/química , Álcool de Polivinil/farmacologia , S-Nitrosoglutationa/farmacologia , S-Nitrosoglutationa/química
2.
Sci Rep ; 14(1): 10117, 2024 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698033

RESUMO

In this research, the hydrophilic structure of multi-walled carbon nanotubes (MWCNTs) was modified by synthesizing polycitric acid (PCA) and attaching folic acid (FA) to create MWCNT-PCA-FA. This modified nanocomplex was utilized as a carrier for the lipophilic compound curcumin (Cur). Characterization techniques including TGA, TEM, and UV-visible spectrophotometry were used to analyze the nanocomplex. The mechanism of cancer cell death induced by MWCNT-PCA-FA was studied extensively using the MTT assay, colony formation analysis, cell cycle assessment via flow cytometry, and apoptosis studies. Furthermore, we assessed the antitumor efficacy of these targeted nanocomplexes following exposure to laser radiation. The results showed that the nanocomposites and free Cur had significant toxicity on melanoma cancer cells (B16F10 cells) while having minimal impact on normal cells (NHDF cells). This selectivity for cancerous cells demonstrates the potential of these compounds as therapeutic agents. Furthermore, MWCNT-PCA-FA/Cur showed superior cytotoxicity compared to free Cur alone. Colony formation studies confirmed these results. The researchers found that MWCNT-FA-PCA/Cur effectively induced programmed cell death. In photothermal analysis, MWCNT-PCA-FA/Cur combined with laser treatment achieved the highest mortality rate. These promising results suggest that this multifunctional therapeutic nanoplatform holds the potential for combination cancer therapies that utilize various established therapeutic methods.


Assuntos
Curcumina , Nanotubos de Carbono , Curcumina/farmacologia , Curcumina/química , Nanotubos de Carbono/química , Linhagem Celular Tumoral , Humanos , Camundongos , Animais , Ácido Fólico/química , Apoptose/efeitos dos fármacos , Melanoma/tratamento farmacológico , Melanoma/patologia , Melanoma/terapia , Terapia Fototérmica/métodos , Antineoplásicos/farmacologia , Antineoplásicos/química , Portadores de Fármacos/química , Sobrevivência Celular/efeitos dos fármacos
3.
J Nanobiotechnology ; 22(1): 224, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702709

RESUMO

Poorly identified tumor boundaries and nontargeted therapies lead to the high recurrence rates and poor quality of life of prostate cancer patients. Near-infrared-II (NIR-II) fluorescence imaging provides certain advantages, including high resolution and the sensitive detection of tumor boundaries. Herein, a cyanine agent (CY7-4) with significantly greater tumor affinity and blood circulation time than indocyanine green was screened. By binding albumin, the absorbance of CY7-4 in an aqueous solution showed no effects from aggregation, with a peak absorbance at 830 nm and a strong fluorescence emission tail beyond 1000 nm. Due to its extended circulation time (half-life of 2.5 h) and high affinity for tumor cells, this fluorophore was used for primary and metastatic tumor diagnosis and continuous monitoring. Moreover, a high tumor signal-to-noise ratio (up to ~ 10) and excellent preferential mitochondrial accumulation ensured the efficacy of this molecule for photothermal therapy. Therefore, we integrated NIR-II fluorescence-guided surgery and intraoperative photothermal therapy to overcome the shortcomings of a single treatment modality. A significant reduction in recurrence and an improved survival rate were observed, indicating that the concept of intraoperative combination therapy has potential for the precise clinical treatment of prostate cancer.


Assuntos
Carbocianinas , Mitocôndrias , Recidiva Local de Neoplasia , Terapia Fototérmica , Neoplasias da Próstata , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Terapia Fototérmica/métodos , Humanos , Animais , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Linhagem Celular Tumoral , Carbocianinas/química , Imagem Óptica/métodos , Camundongos , Cirurgia Assistida por Computador/métodos , Corantes Fluorescentes/química , Camundongos Nus , Camundongos Endogâmicos BALB C , Raios Infravermelhos , Verde de Indocianina/química , Verde de Indocianina/uso terapêutico , Verde de Indocianina/farmacologia
4.
Int J Nanomedicine ; 19: 4121-4136, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38736655

RESUMO

Purpose: This study aims to broaden the application of nano-contrast agents (NCAs) within the realm of the musculoskeletal system. It aims to introduce novel methods, strategies, and insights for the clinical management of ischemic muscle disorders, encompassing diagnosis, monitoring, evaluation, and therapeutic intervention. Methods: We developed a composite encapsulation technique employing O-carboxymethyl chitosan (OCMC) and liposome to encapsulate NCA-containing gold nanorods (GNRs) and perfluoropentane (PFP). This nanoscale contrast agent was thoroughly characterized for its basic physicochemical properties and performance. Its capabilities for in vivo and in vitro ultrasound imaging and photothermal imaging were authenticated, alongside a comprehensive biocompatibility assessment to ascertain its effects on microcirculatory perfusion in skeletal muscle using a murine model of hindlimb ischemia, and its potential to augment blood flow and facilitate recovery. Results: The engineered GNR@OCMC-liposome/PFP nanostructure exhibited an average size of 203.18±1.49 nm, characterized by size uniformity, regular morphology, and a good biocompatibility profile. In vitro assessments revealed NCA's potent photothermal response and its transformation into microbubbles (MBs) under near-infrared (NIR) irradiation, thereby enhancing ultrasonographic visibility. Animal studies demonstrated the nanostructure's efficacy in photothermal imaging at ischemic loci in mouse hindlimbs, where NIR irradiation induced rapid temperature increases and significantly increased blood circulation. Conclusion: The dual-modal ultrasound/photothermal NCA, encapsulating GNR and PFP within a composite shell-core architecture, was synthesized successfully. It demonstrated exceptional stability, biocompatibility, and phase transition efficiency. Importantly, it facilitates the encapsulation of PFP, enabling both enhanced ultrasound imaging and photothermal imaging following NIR light exposure. This advancement provides a critical step towards the integrated diagnosis and treatment of ischemic muscle diseases, signifying a pivotal development in nanomedicine for musculoskeletal therapeutics.


Assuntos
Meios de Contraste , Ouro , Isquemia , Músculo Esquelético , Nanotubos , Ultrassonografia , Animais , Ouro/química , Nanotubos/química , Meios de Contraste/química , Meios de Contraste/farmacologia , Camundongos , Isquemia/diagnóstico por imagem , Isquemia/terapia , Músculo Esquelético/diagnóstico por imagem , Ultrassonografia/métodos , Membro Posterior/irrigação sanguínea , Fluorocarbonos/química , Fluorocarbonos/farmacologia , Lipossomos/química , Quitosana/química , Quitosana/farmacologia , Doenças Musculares/diagnóstico por imagem , Doenças Musculares/terapia , Terapia Fototérmica/métodos , Modelos Animais de Doenças , Humanos , Pentanos
5.
Colloids Surf B Biointerfaces ; 238: 113888, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38599077

RESUMO

Gallium (Ga) is a well-known liquid metals (LMs) that possesses the features, such as fluidity, low viscosity, high electrical and thermal conductivity, and relative low toxicity. Owing to the weak interactions between Ga atoms, Ga LMs can be adopted for fabrication of various Ga LMs-based functional materials via ultrasonic treatment and mechanical grinding. Moreover, many organic compounds/polymers can be coated on the surface of LMs-based materials through coordination between oxidized outlayers of Ga LMs and functional groups of organic components. Over the past decades, different strategies have been reported for synthesizing Ga LMs-based functional materials and their biomedical applications have been intensively investigated. Although some review articles have published over the past few years, a concise review is still needed to advance the latest developments in biomedical fields. The main context can be majorly divided into two parts. In the first section, various strategies for fabrication of Ga LMs-based functional materials via top-down strategies were introduced and discussed. Following that, biomedical applications of Ga LMs-based functional materials were summarized and design Ga LMs-based functional materials with enhanced performance for cancer photothermal therapy (PTT) and PTT combined therapy were highlighted. We trust this review article will be beneficial for scientists to comprehend this promising field and greatly advance future development for fabrication of other Ga LMs-based functional materials with better performance for biomedical applications.


Assuntos
Gálio , Gálio/química , Humanos , Neoplasias/tratamento farmacológico , Terapia Fototérmica/métodos , Animais
6.
Int J Mol Sci ; 25(8)2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38674073

RESUMO

Prostate cancer (PCA) is the second most common cancer diagnosis in men and the fifth leading cause of death worldwide. The conventional treatments available are beneficial to only a few patients and, in those, some present adverse side effects that eventually affect the quality of life of most patients. Thus, there is an urgent need for effective, less invasive and targeted specific treatments for PCA. Photothermal therapy (PTT) is a minimally invasive therapy that provides a localized effect for tumour cell ablation by activating photothermal agents (PTA) that mediate the conversion of the light beam's energy into heat at the site. As tumours are unable to easily dissipate heat, they become more susceptible to temperature increases. In the PTT field, gold nanoparticles (AuNPs) have been attracting interest as PTA. The aim of this study was to formulate AuNPs capable of remaining retained in the tumour and subsequently generating heat at the tumour site. AuNPs were synthesized and characterized in terms of size, polydispersity index (PdI), zeta potential (ZP), morphology and the surface plasmon resonance (SPR). The safety of AuNPs and their efficacy were assessed using in vitro models. A preliminary in vivo safety assessment of AuNPs with a mean size lower than 200 nm was confirmed. The morphology was spherical-like and the SPR band showed good absorbance at the laser wavelength. Without laser, AuNPs proved to be safe both in vitro (>70% viability) and in vivo. In addition, with laser irradiation, they proved to be relatively effective in PCA cells. Overall, the formulation appears to be promising for use in PTT.


Assuntos
Ouro , Nanopartículas Metálicas , Neoplasias da Próstata , Ouro/química , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Masculino , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Humanos , Animais , Terapia Fototérmica/métodos , Linhagem Celular Tumoral , Camundongos , Ressonância de Plasmônio de Superfície , Lasers
7.
Int J Pharm ; 656: 124095, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38588757

RESUMO

Reactive oxygen species (ROS) play a vital role in wound healing process by fighting against invaded bacteria. However, excess ROS at the wound sites lead to oxidative stress that can trigger deleterious effects, causing cell death, tissue damage and chronic inflammation. Therefore, we fabricated a core-shell structured nanomedicine with antibacterial and antioxidant properties via a facile and green strategy. Specifically, Prussian blue (PB) nanozyme was fabricated and followed by coating a layer of epigallocatechin-3-gallate (EGCG)-derived polymer via polyphenolic condensation reaction and self-assembly process, resulting in PB@EGCG. The introduction of PB core endowed EGCG-based polyphenol nanoparticles with excellent NIR-triggered photothermal properties. Besides, owing to multiple enzyme-mimic activity of PB and potent antioxidant capacity of EGCG-derived polymer, PB@EGCG exhibited a remarkable ROS-scavenging ability, mitigated intracellular ROS level and protected cells from oxidative damage. Under NIR irradiation (808 nm, 1.5 W/cm2), PB@EGCG (50 µg/mL) exerted synergistic EGCG-derived polymer-photothermal antibacterial activity against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus). In vivo therapeutic effect was evaluated using a S. aureus-infected rat model indicated PB@EGCG with a prominent bactericidal ability could modulate the inflammatory microenvironment and accelerate wound healing. Overall, this dual-functional nanomedicine provides a promising strategy for efficient antibacterial therapy.


Assuntos
Antibacterianos , Antioxidantes , Catequina , Catequina/análogos & derivados , Escherichia coli , Ferrocianetos , Nanopartículas , Polímeros , Espécies Reativas de Oxigênio , Staphylococcus aureus , Catequina/química , Catequina/farmacologia , Catequina/administração & dosagem , Ferrocianetos/química , Animais , Espécies Reativas de Oxigênio/metabolismo , Antibacterianos/farmacologia , Antibacterianos/administração & dosagem , Antibacterianos/química , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Ratos , Polímeros/química , Nanopartículas/química , Antioxidantes/farmacologia , Antioxidantes/administração & dosagem , Antioxidantes/química , Masculino , Ratos Sprague-Dawley , Humanos , Infecções Estafilocócicas/tratamento farmacológico , Camundongos , Terapia Fototérmica/métodos , Estresse Oxidativo/efeitos dos fármacos
8.
Biomed Pharmacother ; 174: 116586, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38626516

RESUMO

Cancer treatment is presently a significant challenge in the medical domain, wherein the primary modalities of intervention include chemotherapy, radiation therapy and surgery. However, these therapeutic modalities carry side effects. Photothermal therapy (PTT) and photodynamic therapy (PDT) have emerged as promising modalities for the treatment of tumors in recent years. Phototherapy is a therapeutic approach that involves the exposure of materials to specific wavelengths of light, which can subsequently be converted into either heat or Reactive Oxygen Species (ROS) to effectively eradicate cancer cells. Due to the hydrophobicity and lack of targeting of many photoresponsive materials, the use of nano-carriers for their transportation has been extensively explored. Among these nanocarriers, liposomes have been identified as an effective drug delivery system due to their controllability and availability in the biomedical field. By binding photoresponsive materials to liposomes, it is possible to reduce the cytotoxicity of the material and regulate drug release and accumulation at the tumor site. This article provides a comprehensive review of the progress made in cancer therapy using photoresponsive materials loaded onto liposomes. Additionally, the article discusses the potential synergistic treatment through the combination of phototherapy with chemo/immuno/gene therapy using liposomes.


Assuntos
Lipossomos , Neoplasias , Fotoquimioterapia , Humanos , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Animais , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/farmacologia , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Fototerapia/métodos , Terapia Fototérmica/métodos
9.
J Nanobiotechnology ; 22(1): 199, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654266

RESUMO

Considering the high recrudescence and the long-lasting unhealed large-sized wound that affect the aesthetics and cause dysfunction after resection of maxillofacial malignant skin tumors, a groundbreaking strategy is urgently needed. Photothermal therapy (PTT), which has become a complementary treatment of tumors, however, is powerless in tissue defect regeneration. Therefore, a novel multifunctional sodium nitroprusside and Fe2+ ions loaded microneedles (SNP-Fe@MNs) platform was fabricated by accomplishing desirable NIR-responsive photothermal effect while burst releasing nitric oxide (NO) after the ultraviolet radiation for the ablation of melanoma. Moreover, the steady releasing of NO in the long term by the platform can exert its angiogenic effects via upregulating multiple related pathways to promote tissue regeneration. Thus, the therapeutic dilemma caused by postoperative maxillofacial skin malignancies could be conquered through promoting tumor cell apoptosis via synergistic PTT-gas therapy and subsequent regeneration process in one step. The bio-application of SNP-Fe@MNs could be further popularized based on its ideal bioactivity and appealing features as a strategy for synergistic therapy of other tumors occurred in skin.


Assuntos
Melanoma , Óxido Nítrico , Terapia Fototérmica , Neoplasias Cutâneas , Animais , Terapia Fototérmica/métodos , Camundongos , Neoplasias Cutâneas/terapia , Melanoma/terapia , Óxido Nítrico/metabolismo , Óxido Nítrico/farmacologia , Linhagem Celular Tumoral , Agulhas , Humanos , Nitroprussiato/farmacologia , Apoptose/efeitos dos fármacos , Pele , Ferro/química , Raios Ultravioleta
10.
Int J Implant Dent ; 10(1): 19, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38656614

RESUMO

PURPOSE: Dental implants have been successfully implemented as a treatment for tooth loss. However, peri-implantitis, an inflammatory reaction owing to microbial deposition around the implant, can lead to implant failure. So, it is necessary to treat peri-implantitis. Therefore, this numerical study is aimed at investigating conditions for treating peri-implantitis. METHODS: Photothermal therapy, a laser treatment method, utilizes photothermal effect, in which light is converted to heat. This technique has advantage of selectively curing inflamed tissues by increasing their temperature. Accordingly, herein, photothermal effect on peri-implantitis is studied through numerical analysis with using Arrhenius damage integral and Arrhenius thermal damage ratio. RESULTS: Through numerical analysis on peri-implantitis treatment, we explored temperature changes under varied laser settings (laser power, radius, irradiation time). We obtained the temperature distribution on interface of artificial tooth root and inflammation and determined whether temperature exceeds or does not exceed 47℃ to know which laser power affects alveolar bone indirectly. We defined the Arrhenius thermal damage ratio as a variable and determined that the maximum laser power that does not exceed 47℃ at the AA' line is 1.0 W. Additionally, we found that the value of the Arrhenius thermal damage ratio is 0.26 for a laser irradiation time of 100 s and 0.50 for 500 s. CONCLUSION: The result of this numerical study indicates that the Arrhenius thermal damage ratio can be used as a standard for determining the treatment conditions to help assisted laser treatment for peri-implantitis in each numerical analysis scenario.


Assuntos
Peri-Implantite , Terapia Fototérmica , Peri-Implantite/terapia , Peri-Implantite/radioterapia , Humanos , Terapia Fototérmica/métodos , Temperatura , Implantes Dentários/efeitos adversos , Lasers
11.
J Nanobiotechnology ; 22(1): 202, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658952

RESUMO

Multi-modal combination therapy is regarded as a promising approach to cancer treatment. Combining chemotherapy and phototherapy is an essential multi-modal combination therapy endeavor. Ivermectin (IVM) is a potent antiparasitic agent identified as having potential antitumor properties. However, the fact that it induces protective autophagy while killing tumor cells poses a challenge to its further application. IR780 iodide (IR780) is a near-infrared (NIR) dye with outstanding photothermal therapy (PTT) and photodynamic therapy (PDT) effects. However, the hydrophobicity, instability, and low tumor uptake of IR780 limit its clinical applications. Here, we have structurally modified IR780 with hydroxychloroquine, an autophagy inhibitor, to synthesize a novel compound H780. H780 and IVM can form H780-IVM nanoparticles (H-I NPs) via self-assembly. Using hyaluronic acid (HA) to modify the H-I NPs, a novel nano-delivery system HA/H780-IVM nanoparticles (HA/H-I NPs) was synthesized for chemotherapy-phototherapy of colorectal cancer (CRC). Under NIR laser irradiation, HA/H-I NPs effectively overcame the limitations of IR780 and IVM and exhibited potent cytotoxicity. In vitro and in vivo experiment results showed that HA/H-I NPs exhibited excellent anti-CRC effects. Therefore, our study provides a novel strategy for CRC treatment that could enhance chemo-phototherapy by modulating autophagy.


Assuntos
Autofagia , Neoplasias Colorretais , Reposicionamento de Medicamentos , Ivermectina , Nanopartículas , Autofagia/efeitos dos fármacos , Animais , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/terapia , Humanos , Camundongos , Nanopartículas/química , Ivermectina/farmacologia , Ivermectina/química , Linhagem Celular Tumoral , Indóis/química , Indóis/farmacologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Fotoquimioterapia/métodos , Antineoplásicos/farmacologia , Antineoplásicos/química , Fototerapia/métodos , Ácido Hialurônico/química , Hidroxicloroquina/farmacologia , Hidroxicloroquina/química , Terapia Fototérmica/métodos
12.
J Nanobiotechnology ; 22(1): 205, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658965

RESUMO

The elevated level of hydrogen sulfide (H2S) in colon cancer hinders complete cure with a single therapy. However, excessive H2S also offers a treatment target. A multifunctional cascade bioreactor based on the H2S-responsive mesoporous Cu2Cl(OH)3-loaded hypoxic prodrug tirapazamine (TPZ), in which the outer layer was coated with hyaluronic acid (HA) to form TPZ@Cu2Cl(OH)3-HA (TCuH) nanoparticles (NPs), demonstrated a synergistic antitumor effect through combining the H2S-driven cuproptosis and mild photothermal therapy. The HA coating endowed the NPs with targeting delivery to enhance drug accumulation in the tumor tissue. The presence of both the high level of H2S and the near-infrared II (NIR II) irradiation achieved the in situ generation of photothermic agent copper sulfide (Cu9S8) from the TCuH, followed with the release of TPZ. The depletion of H2S stimulated consumption of oxygen, resulting in hypoxic state and mitochondrial reprogramming. The hypoxic state activated prodrug TPZ to activated TPZ (TPZ-ed) for chemotherapy in turn. Furthermore, the exacerbated hypoxia inhibited the synthesis of adenosine triphosphate, decreasing expression of heat shock proteins and subsequently improving the photothermal therapy. The enriched Cu2+ induced not only cuproptosis by promoting lipoacylated dihydrolipoamide S-acetyltransferase (DLAT) heteromerization but also performed chemodynamic therapy though catalyzing H2O2 to produce highly toxic hydroxyl radicals ·OH. Therefore, the nanoparticles TCuH offer a versatile platform to exert copper-related synergistic antitumor therapy.


Assuntos
Cobre , Ácido Hialurônico , Sulfeto de Hidrogênio , Mitocôndrias , Nanopartículas , Terapia Fototérmica , Pró-Fármacos , Tirapazamina , Terapia Fototérmica/métodos , Sulfeto de Hidrogênio/metabolismo , Sulfeto de Hidrogênio/farmacologia , Animais , Cobre/química , Cobre/farmacologia , Camundongos , Humanos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Pró-Fármacos/farmacologia , Pró-Fármacos/química , Tirapazamina/farmacologia , Tirapazamina/química , Nanopartículas/química , Ácido Hialurônico/química , Linhagem Celular Tumoral , Neoplasias do Colo/terapia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/tratamento farmacológico , Camundongos Endogâmicos BALB C , Antineoplásicos/farmacologia , Antineoplásicos/química , Camundongos Nus
13.
J Med Chem ; 67(9): 7431-7442, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38664896

RESUMO

Since hydrogen sulfide (H2S) is an important endogenous gaseous mediator, therapeutic manipulation of H2S is promising for anticancer treatment. In this work, we develop a novel theranostic nanoplatform with H2S-specific and photocontrolled synergistic activation for imaging-guided H2S depletion and downregulation along with promoted photothermal therapy. Such a nanoplatform is fabricated by integration of a H2S-responsive molecule probe that can generate a cystathionine-ß-synthase (CBS) inhibitor AOAA and a photothermal transducer into an NIR-light-responsive container. Our nanoplatform can turn on NIR fluorescence specifically in H2S-rich cancers, guiding further laser irradiation. Furthermore, prominent conversion of photoenergy into heat guarantees special container melting with controllable AOAA release for H2S-level downregulation. This smart regulation of the endogenous H2S level amplifies the PTT therapeutic effect, successfully suppressing colorectal tumor in living mice under NIR fluorescence imaging guidance. Thus, we believe that this nanoplatform may provide a powerful tool toward H2S-concerned cancer treatment with an optimized diagnostic and therapeutic effect.


Assuntos
Neoplasias Colorretais , Regulação para Baixo , Sulfeto de Hidrogênio , Terapia Fototérmica , Sulfeto de Hidrogênio/metabolismo , Sulfeto de Hidrogênio/química , Animais , Terapia Fototérmica/métodos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/terapia , Neoplasias Colorretais/patologia , Humanos , Camundongos , Regulação para Baixo/efeitos dos fármacos , Cistationina beta-Sintase/metabolismo , Cistationina beta-Sintase/antagonistas & inibidores , Imagem Óptica , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Raios Infravermelhos , Linhagem Celular Tumoral , Nanomedicina Teranóstica/métodos
14.
J Nanobiotechnology ; 22(1): 214, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38689291

RESUMO

Combination of tumor immunotherapy with photothermal therapy (PTT) is a feasible tactic to overcome the drawback of immunotherapy such as poor immune response. Via triggering the immunogenic cells death (ICD), PTT can stimulate the activity of immune cells, but meanwhile, the level of adenosine is elevated via the CD73-induced decomposition of ATP which is overexpressed accompanying with the PTT process, resulting in negative feedback to impair the immune stimulation. Herein, we developed a novel biomimetic photothermal nanodrug to specifically block CD73 for inhibition of adenosine production and more efficient priming of the suppressive immune microenvironments. The nanodrug, named as AptEM@CBA, is constructed by encapsulation of photothermal agent black phosphorus quantum dots (BPQDs) and selective CD73 inhibitor α, ß-Methyleneadenosine 5'-diphosphate (AMPCP) in chitosan nanogels, which are further covered with aptamer AS1411 modified erythrocyte membrane (EM) for biomimetic camouflage. With AS1411 induced active targeting and EM induced long blood circulation time, the enrichment of the nanodrug tumor sites is promoted. The photothermal treatment promotes the maturation of dendritic cells. Meanwhile, the release of AMPCP suppress the adenosine generation via CD73 blockade, alleviating the impairment of adenosine to dendritic cells and suppressing regulatory T cells, synergically stimulate the activity of T cells. The combination of CD73 blockade with PTT, not only suppresses the growth of primary implanted tumors, but also boosts strong antitumor immunity to inhibit the growth of distal tumors, providing good potential for tumor photoimmunotherapy.


Assuntos
5'-Nucleotidase , Difosfato de Adenosina , Adenosina , Imunoterapia , Terapia Fototérmica , Animais , Humanos , Camundongos , 5'-Nucleotidase/antagonistas & inibidores , Adenosina/química , Adenosina/análogos & derivados , Adenosina/farmacologia , Difosfato de Adenosina/análogos & derivados , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Biomimética/métodos , Linhagem Celular Tumoral , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Imunoterapia/métodos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Nanopartículas/química , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Terapia Fototérmica/métodos , Pontos Quânticos/química , Microambiente Tumoral/efeitos dos fármacos , Masculino
15.
Biomaterials ; 308: 122565, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38603823

RESUMO

As bacterial keratitis progresses rapidly, prompt intervention is necessary. Current diagnostic processes are time-consuming and invasive, leading to improper antibiotics for treatment. Therefore, innovative strategies for diagnosing and treating bacterial keratitis are urgently needed. In this study, Cu2-xSe@BSA@NTRP nanoparticles were developed by loading nitroreductase-responsive probes (NTRPs) onto Cu2-xSe@BSA. These nanoparticles exhibited integrated fluorescence imaging and antibacterial capabilities. In vitro and in vivo experiments showed that the nanoparticles produced responsive fluorescence signals in bacteria within 30 min due to an interaction between the released NTRP and bacterial endogenous nitroreductase (NTR). When combined with low-temperature photothermal therapy (PTT), the nanoparticles effectively eliminated E. coli and S. aureus, achieved antibacterial efficacy above 95% and facilitated the re-epithelialization process at the corneal wound site in vivo. Overall, the Cu2-xSe@BSA@NTRP nanoparticles demonstrated potential for rapid, noninvasive in situ diagnosis, treatment, and visualization assessment of therapy effectiveness in bacterial keratitis.


Assuntos
Antibacterianos , Escherichia coli , Ceratite , Nanopartículas , Nitrorredutases , Animais , Nitrorredutases/metabolismo , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/uso terapêutico , Nanopartículas/química , Ceratite/tratamento farmacológico , Ceratite/microbiologia , Escherichia coli/efeitos dos fármacos , Imagem Óptica/métodos , Staphylococcus aureus/efeitos dos fármacos , Camundongos , Terapia Fototérmica/métodos , Humanos , Cobre/química
16.
Int J Biol Macromol ; 266(Pt 2): 131359, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38580018

RESUMO

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.


Assuntos
Quitosana , Glutationa , Nanopartículas , Fotoquimioterapia , Fármacos Fotossensibilizantes , Terapia Fototérmica , Polietilenoglicóis , Quitosana/química , Fotoquimioterapia/métodos , Animais , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Glutationa/metabolismo , Polietilenoglicóis/química , Camundongos , Nanopartículas/química , Terapia Fototérmica/métodos , Linhagem Celular Tumoral , Verde de Indocianina/química , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Oxigênio Singlete/metabolismo , Humanos , Apoptose/efeitos dos fármacos , Indóis/química , Indóis/farmacologia , Polímeros/química
17.
Int J Mol Sci ; 25(8)2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38673726

RESUMO

Bone tumors, particularly osteosarcoma, are prevalent among children and adolescents. This ailment has emerged as the second most frequent cause of cancer-related mortality in adolescents. Conventional treatment methods comprise extensive surgical resection, radiotherapy, and chemotherapy. Consequently, the management of bone tumors and bone regeneration poses significant clinical challenges. Photothermal tumor therapy has attracted considerable attention owing to its minimal invasiveness and high selectivity. However, key challenges have limited its widespread clinical use. Enhancing the tumor specificity of photosensitizers through targeting or localized activation holds potential for better outcomes with fewer adverse effects. Combinations with chemotherapies or immunotherapies also present avenues for improvement. In this review, we provide an overview of the most recent strategies aimed at overcoming the limitations of photothermal therapy (PTT), along with current research directions in the context of bone tumors, including (1) target strategies, (2) photothermal therapy combined with multiple therapies (immunotherapies, chemotherapies, and chemodynamic therapies, magnetic, and photodynamic therapies), and (3) bifunctional scaffolds for photothermal therapy and bone regeneration. We delve into the pros and cons of these combination methods and explore current research focal points. Lastly, we address the challenges and prospects of photothermal combination therapy.


Assuntos
Neoplasias Ósseas , Raios Infravermelhos , Terapia Fototérmica , Humanos , Neoplasias Ósseas/terapia , Terapia Fototérmica/métodos , Raios Infravermelhos/uso terapêutico , Animais , Fármacos Fotossensibilizantes/uso terapêutico , Osteossarcoma/terapia , Osteossarcoma/patologia , Terapia Combinada/métodos , Imunoterapia/métodos , Fotoquimioterapia/métodos , Regeneração Óssea
18.
Biomed Pharmacother ; 174: 116486, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38520865

RESUMO

Recurrence and metastasis of gastric cancer is a major therapeutic challenge for treatment. The presence of cancer stem cells (CSCs) is a major obstacle to the success of current cancer therapy, often leading to treatment resistance and tumor recurrence and metastasis. Therefore, it is important to develop effective strategies to eradicate CSCs. In this study, we developed a combined therapeutic strategy of photothermal therapy (PTT) and gastric cancer stem cells (GCSCs) inhibition by successfully synthesizing nanoliposomes loaded with IR780 (photosensitizer) and EN4 (c-Myc inhibitor). The nanocomposites are biocompatible and exhibit superior photoacoustic (PA) imaging properties. Under laser irradiation, IR780-mediated PTT effectively and rapidly killed tumor cells, while EN4 synergistically inhibited the self-renewal and stemness of GCSCs by suppressing the expression and activity of the pluripotent transcription factor c-Myc, preventing the tumor progression of gastric cancer. This Nano-EN-IR@Lip is expected to be a novel clinical nanomedicine for the integration of gastric cancer diagnosis, treatment and prevention.


Assuntos
Lipossomos , Células-Tronco Neoplásicas , Fármacos Fotossensibilizantes , Terapia Fototérmica , Neoplasias Gástricas , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia , Neoplasias Gástricas/tratamento farmacológico , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Humanos , Terapia Fototérmica/métodos , Animais , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/administração & dosagem , Indóis/farmacologia , Indóis/química , Nanopartículas/química , Camundongos Nus , Terapia Combinada , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Nanocompostos/química
19.
Int J Biol Macromol ; 266(Pt 1): 130838, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38521322

RESUMO

Innovative antibacterial therapies using nanomaterials, such as photothermal (PTT) and photodynamic (PDT) treatments, have been developed for treating wound infections. However, creating secure wound dressings with these therapies faces challenges. The primary focus of this study is to prepare an antibacterial nanofiber dressing that effectively incorporates stable loads of functional nanoparticles and demonstrates an efficient synergistic effect between PTT and PDT. Herein, a composite nanofiber mat was fabricated, integrating spherical molybdenum disulfide (MoS2) nanoparticles. MoS2 was deposited onto polylactic acid (PLA) nanofiber mats using vacuum filtration, which was further stabilized by sodium carboxymethyl cellulose (CMC) adhesion and glutaraldehyde (GA) cross-linking. The composite nanofibers demonstrated synergistic antibacterial effects under NIR light irradiation, and the underlying mechanism was explored. They induce bacterial membrane permeability, protein leakage, and intracellular reactive oxygen species (ROS) elevation, ultimately leading to >95 % antibacterial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), which is higher than that of single thermotherapy (almost no antibacterial activity) or ROS therapy (about 80 %). In addition, the composite nanofiber mats exhibited promotion effects on infected wound healing in vivo. This study demonstrates the great prospects of composite nanofiber dressings in clinical treatment of bacterial-infected wounds.


Assuntos
Antibacterianos , Carboximetilcelulose Sódica , Dissulfetos , Escherichia coli , Molibdênio , Nanofibras , Fotoquimioterapia , Staphylococcus aureus , Molibdênio/química , Molibdênio/farmacologia , Dissulfetos/química , Dissulfetos/farmacologia , Nanofibras/química , Antibacterianos/farmacologia , Antibacterianos/química , Fotoquimioterapia/métodos , Carboximetilcelulose Sódica/química , Carboximetilcelulose Sódica/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Animais , Escherichia coli/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Terapia Fototérmica/métodos , Bandagens
20.
Ultrasound Med Biol ; 50(6): 869-881, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38538442

RESUMO

OBJECTIVE: Novel strategies for treating triple-negative breast cancer (TNBC) are ongoing because of the lack of standard-of-care treatment. Nanoframed materials with a protein pillar are considered a valuable tool for designing multigoals of energy-absorbing/medication cargo and are a bridge to cross-conventional treatment strategies. METHODS: Nanobioconjugates of gold nanoclusters-bovine serum albumin (AuNCs-BSA) and doxorubicin-AuNCs-BSA (Dox-AuNCs-BSA) were prepared and employed as a simultaneous double photosensitizer/sonosensitizer and triple chemotherapeutic/photosensitizer/sonosensitizer, respectively. RESULTS: The highly stable AuNCs-BSA and Dox-AuNCs-BSA have ζ potentials of -29 and -18 mV, respectively, and represent valuable photothermal and sonodynamic activities for the combination of photothermal therapy and sonodynamic therapy (PTT/SDT) and synchronized chemotherapy/photothermal therapy/sonodynamic therapy (CTX/PTT/SDT) of human TNBC cells, respectively. The efficiency of photothermal conversion of AuNCs-BSA was calculated to be a promising value of 32.9%. AuNCs-BSA and Dox-AuNCs-BSA were activated on either laser light irradiation or ultrasound exposure with the highest efficiency on the combination of both types of radiation. CTX/PTT/SDT of MCF-7 and MDA-MB-231 breast cancer cell lines by Dox-AuNCs-BSA were evaluated with the MTT cell proliferation assay and found to progress synergistically. CONCLUSION: Results of the MTT assay, detection of the generation of intracellular reactive oxygen species and occurrence of apoptosis in the cells confirmed that CTX/PTT/SDT by Dox-AuNCs-BSA was attained with lower needed doses of the drug and improved tumor cell ablation, which would result in the enhancement of therapeutic efficacy and overcoming of therapeutic resistance.


Assuntos
Antibióticos Antineoplásicos , Doxorrubicina , Ouro , Terapia Fototérmica , Soroalbumina Bovina , Neoplasias de Mama Triplo Negativas , Terapia por Ultrassom , Humanos , Ouro/química , Doxorrubicina/farmacologia , Neoplasias de Mama Triplo Negativas/terapia , Feminino , Terapia por Ultrassom/métodos , Terapia Fototérmica/métodos , Antibióticos Antineoplásicos/farmacologia , Nanoconjugados/química , Terapia Combinada , Nanopartículas Metálicas , Receptores de Estrogênio , Linhagem Celular Tumoral , Neoplasias da Mama/terapia
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