RESUMEN

Photothermal therapy (PTT) provides a great prospect for noninvasive cancer therapy. However, it is still highly challenging to construct photothermal agents (PTAs) with the desired performances for imaging-guided PTT applications. Herein, a D-A-D-type naphthalene diamine (NDI)-based photothermal nano-PTAs NDS-BPN NP with near-infrared region (NIR) emission at 822 nm, aggregation-induced emission (AIE), high photothermal conversion efficiency (55.05%), and excellent photothermal stability is successfully designed and prepared through a simple two-step engineering method by using a new AIE molecule NDS-BPN and DSPE-PEG2000 as precursors. The prepared PTT nanoagents NDS-BPN NPs have been further applied for efficient photothermal ablation of cancer cells in vitro and also achieved the NIR fluorescent image-guided PTT tumor therapy in vivo with satisfactory results. We believe that this work provides an attractive NIR AIE NDI-based nano-PTA for the phototherapy of tumors as well as develops the construction strategy of NDI molecular-based photothermal nanoagents with desired performances for imaging-guided PTT.

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

RESUMEN

Gold-based nanoparticles for surface-enhanced Raman scattering (SERS) imaging show great potential for precise tumor detection and photothermal therapy (PTT). However, the metabolizability of gold nanoparticles (Au NPs) raises big concerns. Herein, we designed a core-shelled nanostructure of copper sulfide (CuS)-coated Au NPs with surface pegylation (PEG-Au@CuS NSs). The excreted Au in the gallbladders at 1 h and 4 h in mice injected with PEG-Au@CuS NSs was 8.2- and 19.1-fold of that with the pegylated Au NPs (PEG-AuNPs) of the same Au particle size, respectively. By loading the Raman reporter 3,3'-Diethylthiatricarbocyanine iodide (DTTC) in the core-shell junction of PEG-Au@CuS NSs, the PEG-Au-DTTC@CuS NSs exhibited the Raman signal-to-noise (S/N) ratio of 4.01 after 24 h of intravenous (IV) injection in the mice bearing an orthotopic CT26-Luc colon tumor. By contrast, the DTTC-coated PEG-AuNPs (PEG-Au-DTTC NPs) achieved an S/N ratio of 2.71. Moreover, PEG-Au-DTTC@CuS NSs exhibited an increased photothermal conversion effect compared with PEG-Au-DTTC NPs excited with an 808-nm laser. PEG-Au-DTTC@CuS NSs enabled intraoperative SERS image-guided photothermal therapy for a complete cure of the colon tumor-bearing mice. Our data demonstrated that the PEG-Au-DTTC@CuS NSs are promising intraoperative Raman image-guided theranostic nanoplatform with enhanced hepatobiliary excretion.

RESUMEN

Biofilm-associated infections pose a significant challenge in healthcare, constituting 80% of bacterial infections and often leading to persistent, chronic conditions. Conventional antibiotics struggle with efficacy against these infections due to the high tolerance and resistance induced by bacterial biofilm barriers. Two-dimensional nanomaterials, such as those from the graphene family, boron nitride, molybdenum disulfide (MoS2), MXene, and black phosphorus, hold immense potential for combating biofilms. These nanomaterial-based antimicrobial strategies are novel tools that show promise in overcoming resistant bacteria and stubborn biofilms, with the ability to circumvent existing drug resistance mechanisms. This review comprehensively summarizes recent developments in two-dimensional nanomaterials, as both therapeutics and nanocarriers for precision antibiotic delivery, with a specific focus on nanoplatforms coupled with photothermal/photodynamic therapy in the elimination of bacteria and penetrating and/or ablating biofilm. This review offers important insight into recent advances and current limitations of current antibacterial nanotherapeutic approaches, together with a discussion on future developments in the field, for the overall benefit of public health.

RESUMEN

Cancer immunotherapy has been developed to improve therapeutic effects for patients by activating the innate immune stimulator of interferon gene (STING) pathway. However, most patients cannot benefit from this therapy, mainly due to the problems of excessively low immune responses and lack of tumor specificity. Herein, we report a solution to these two problems by developing a bifunctional platform of black phosphorus quantum dots (BPQDs) for STING agonists. Specifically, BPQDs could connect targeted functional groups and regulate surface zeta potential by coordinating metal ions to increase loading (over 5 times) while maintaining high universality (7 STING agonists). The controlled release of STING agonists enabled specific interactions with their proteins, activating the STING pathway and stimulating the secretion release of immunosuppressive factors by phosphorylating TBK1 and IFN-IRF3 and secreting high levels of immunostimulatory cytokines, including IL-6, IFN-α, and IFN-ß. Moreover, the immunotherapy was enhanced was enhanced mild photothermal therapy (PTT) of BPQDs platform, producing enough T cells to eliminate tumors and prevent tumor recurrence. This work facilitates further research on targeted delivery of small-molecule immune drugs to enhance the development of clinical immunotherapy.

Asunto(s)

Inmunoterapia , Proteínas de la Membrana , Fósforo , Puntos Cuánticos , Puntos Cuánticos/química , Fósforo/química , Inmunoterapia/métodos , Animales , Proteínas de la Membrana/agonistas , Humanos , Ratones , Línea Celular Tumoral , Citocinas/metabolismo , Terapia Fototérmica/métodos , Ratones Endogámicos C57BL , Sistemas de Liberación de Medicamentos , Femenino

RESUMEN

Indocyanine green is an FDA-approved fluorescent imaging dye used for determining cardiac output, hepatic function, liver blood flow, and retinal perfusion. It has been investigated preclinically in photoacoustic imaging and photothermal therapy (PTT); however, ICG photodegradation limits its biomedical applications. An aggregated form of ICG, known as J-aggregate (IJA), exhibits superior photoacoustic signals and thermal stability than the monomeric ICG. Nevertheless, IJA still suffers from low stability in the biological milieu, and short in vivo blood circulation. To address these limitations, a range of nanocarriers have been developed to enhance IJA stability and performance. This review focuses on IJA potentials and limitations, besides the recent development of IJA-loaded nanocarriers, particularly for cancer imaging and therapy.

Asunto(s)

Verde de Indocianina , Nanomedicina Teranóstica , Verde de Indocianina/administración & dosificación , Humanos , Animales , Nanomedicina Teranóstica/métodos , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Neoplasias/diagnóstico por imagen , Nanopartículas , Colorantes Fluorescentes/química , Colorantes Fluorescentes/administración & dosificación , Técnicas Fotoacústicas/métodos , Portadores de Fármacos/química

RESUMEN

Stimulation of the innate immune stimulator of interferon genes (STING) pathway has been shown to boost anti-tumour immunity. Nevertheless, the systemic delivery of STING agonists to the tumour presents challenges. Therefore, we designed a cyclic dinucleotide (CDN)-based drug delivery system (DDS) combined photothermal therapy (PTT)/photodynamic therapy (PDT)/immunotherapy for cutaneous melanoma. We coencapsulated a reactive oxygen species (ROS)-responsive prodrug thioketone-linked CDN (TK-CDN), and photoresponsive agents chlorin E6 (Y6) within mitochondria-targeting reagent triphenylphosphonium (TPP)-modified liposomes (Lipo/TK-CDN/TPP/Y6). Lipo/TK-CDN/TPP/Y6 exhibited a photothermal effect similar to Y6, along with a superior cellular uptake rate. Upon endocytosis by B16F10 cells, Lipo/TK-CDN/TPP/Y6 generated large amounts of ROS under laser irradiation for PDT. Mice bearing B16F10 tumours were intravenously injected with Lipo/TK-CDN/TPP/Y6 and exposed to irradiation, resulting in a substantial inhibition of tumour growth. Exploration of the mechanism of anti-tumour action showed that Lipo/TK-CDN/TPP/Y6 had a stronger stimulation of STING activation and anti-tumour immune cell infiltration compared to other groups. Hence, the Lipo/TK-CDN/TPP/Y6 nanoparticles offer great potential as a DDS for targeted and on-demand drug release at tumour sites. These nanoparticles exhibit promise as a candidate for precise and controllable combination therapy in the treatment of tumours.

Asunto(s)

Clorofilidas , Liposomas , Melanoma Experimental , Nanopartículas , Fotoquimioterapia , Porfirinas , Profármacos , Especies Reactivas de Oxígeno , Neoplasias Cutáneas , Animales , Ratones , Nanopartículas/química , Fotoquimioterapia/métodos , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Especies Reactivas de Oxígeno/metabolismo , Profármacos/farmacología , Profármacos/administración & dosificación , Profármacos/química , Melanoma Experimental/tratamiento farmacológico , Porfirinas/farmacología , Porfirinas/administración & dosificación , Porfirinas/química , Línea Celular Tumoral , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/administración & dosificación , Compuestos Organofosforados/química , Compuestos Organofosforados/farmacología , Compuestos Organofosforados/administración & dosificación , Terapia Fototérmica/métodos , Ratones Endogámicos C57BL , Inmunoterapia/métodos , Melanoma/tratamiento farmacológico , Melanoma/patología , Sistemas de Liberación de Medicamentos , Humanos , Melanoma Cutáneo Maligno

RESUMEN

An innovative nanozyme, iron-doped polydopamine (Fe-PDA), which integrates iron ions into a PDA matrix, conferred peroxidase-mimetic activity and achieved a substantial photothermal conversion efficiency of 43.5 %. Fe-PDA mediated the catalysis of H2O2 to produce toxic hydroxyl radicals (•OH), thereby facilitating lipid peroxidation in tumour cells and inducing ferroptosis. Downregulation of solute carrier family 7 no. 11 (SLC7A11) and solute carrier family 3 no. 2 (SLC3A2) in System Xc- resulted in decreased intracellular glutathione (GSH) production and inactivation of the nuclear factor erythroid 2-related factor 2 (NRF2)-glutathione peroxidase 4 (GPX4) pathway, contributing to ferroptosis. Moreover, the application of photothermal therapy (PTT) enhanced the effectiveness of chemodynamic therapy (CDT), accelerating the Fenton reaction for targeted tumour eradication while sparing adjacent non-cancerous tissues. In vivo experiments revealed that Fe-PDA significantly hampered tumour progression in mice, emphasizing the potential of the dual-modality treatment combining CDT and PTT for future clinical oncology applications.

Asunto(s)

Ferroptosis , Indoles , Hierro , Neoplasias Hepáticas , Terapia Fototérmica , Polímeros , Indoles/química , Indoles/farmacología , Ferroptosis/efectos de los fármacos , Polímeros/química , Polímeros/farmacología , Animales , Humanos , Hierro/química , Hierro/farmacología , Ratones , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Ratones Endogámicos BALB C , Peróxido de Hidrógeno/farmacología , Peróxido de Hidrógeno/metabolismo , Nanopartículas/química , Proliferación Celular/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/química , Tamaño de la Partícula , Ensayos de Selección de Medicamentos Antitumorales , Propiedades de Superficie

RESUMEN

Breast cancer is a malignant tumor with a high mortality rate among women. Therefore, it is necessary to develop novel therapies to effectively treat this disease. In this study, iron selenide nanorods (FeSe2 NRs) were designed for use in magnetic hyperthermic, photothermal, and chemodynamic therapy (MHT/PTT/CDT) for breast cancer. To illustrate their efficacy, FeSe2 NRs were modified with the chemotherapeutic agent methotrexate (MTX). MTX-modified FeSe2 (FeSe2-MTX) exhibited excellent controlled drug release properties. Fe2+ released from FeSe2 NRs induced the release of •OH from H2O2 via a Fenton/Fenton-like reaction, enhancing the efficacy of CDT. Under alternating magnetic field (AMF) stimulation and 808 nm laser irradiation, FeSe2-MTX exerted potent hyperthermic and photothermal effects by suppressing tumor growth in a breast cancer nude mouse model. In addition, FeSe2 NRs can be used for magnetic resonance imaging in vivo by incorporating their superparamagnetic characteristics into a single nanomaterial. Overall, we presented a novel technique for the precise delivery of functional nanosystems to tumors that can enhance the efficacy of breast cancer treatment.

Asunto(s)

Neoplasias de la Mama , Hipertermia Inducida , Metotrexato , Ratones Desnudos , Nanotubos , Metotrexato/química , Metotrexato/farmacología , Animales , Nanotubos/química , Ratones , Femenino , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Ratones Endogámicos BALB C , Terapia Fototérmica , Hierro/química , Compuestos de Selenio/química , Compuestos de Selenio/farmacología , Compuestos de Selenio/efectos de la radiación , Línea Celular Tumoral , Rayos Infrarrojos

RESUMEN

Phototherapies are promising for noninvasive treatment of aggressive tumors, especially when combining heat induction and oxidative processes. Herein, we show enhanced phototoxicity of gold shell-isolated nanorods conjugated with toluidine blue-O (AuSHINRs@TBO) against human colorectal tumor cells (Caco-2) with synergic effects of photothermal (PTT) and photodynamic therapies (PDT). Mitochondrial metabolic activity tests (MTT) performed on Caco-2 cell cultures indicated a photothermal effect from AuSHINRs owing to enhanced light absorption from the localized surface plasmon resonance (LSPR). The phototoxicity against Caco-2 cells was further increased with AuSHINRs@TBO where oxidative processes, such as hydroperoxidation, were also present, leading to a cell viability reduction from 85.5 to 39.0%. The molecular-level mechanisms responsible for these effects were investigated on bioinspired tumor membranes using Langmuir monolayers of Caco-2 lipid extract. Polarization-modulation infrared reflection-absorption spectroscopy (PM-IRRAS) revealed that the AuSHINRs@TBO incorporation is due to attractive electrostatic interactions with negatively charged groups of the Caco-2 lipid extract, resulting in the expansion of surface pressure isotherms. Upon irradiation, Caco-2 lipid extract monolayers containing AuSHINRs@TBO (1:1 v/v) exhibited ca. 1.0% increase in surface area. This is attributed to the generation of reactive oxygen species (ROS) and their interaction with Caco-2 lipid extract monolayers, leading to hydroperoxide formation. The oxidative effects are facilitated by AuSHINRs@TBO penetration into the polar groups of the extract, allowing oxidative reactions with carbon chain unsaturations. These mechanisms are consistent with findings from confocal fluorescence microscopy, where the Caco-2 plasma membrane was the primary site of the cell death induction process.

RESUMEN

Combining chemodynamic therapy (CDT) with photothermal therapy (PTT) has developed as a promising approach for cancer treatment, as it enhances therapeutic efficiency through redox reactions and external laser induction. In this study, we designed metal organic framework (MOF) -derived Cu5Zn8/HPCNC through a carbonization process and decorated them with gold nanoparticles (Au@Cu5Zn8/HPCNC). The resulting nanoparticles were employed as a photothermal agent and Fenton catalyst. The Fenton reaction facilitated the conversation of Cu2+ to Cu+ through reaction with local H2O2, generating reactive hydroxyl radicals (·OH) with potent cytotoxic effects. To enhance the Fenton-like reaction and achieve combined therapy, laser irradiation of the Au@Cu5Zn8/HPCNC induced efficient photothermal therapy by generating localized heat. With a significantly increased absorption of Au@Cu5Zn8/HPCNC at 808 nm, the photothermal efficiency was determined to be 57.45 %. Additionally, Au@Cu5Zn8/HPCNC demonstrated potential as a contrast agent for magnetic resonance imaging (MRI) of cancers. Furthermore, the synergistic combination of PTT and CDT significantly inhibited tumor growth. This integrated approach of PTT and CDT holds great promise for cancer therapy, offering enhanced CDT and modulation of the tumor microenvironment (TME), and opening new avenues in the fight against cancer.

Asunto(s)

Nanopartículas del Metal , Estructuras Metalorgánicas , Oro , Nanopartículas del Metal/uso terapéutico , Terapia Fototérmica , Porosidad , Microambiente Tumoral , Carbono , Imagen por Resonancia Magnética , Zinc

RESUMEN

Single-molecule-based synergistic phototherapy holds great potential for antimicrobial treatment. Herein, we report an orthogonal molecular cationization strategy to improve the reactive oxygen species (ROS) and hyperthermia generation of heptamethine cyanine (Cy7) for photodynamic and photothermal treatments of bacterial infections. Cationic pyridine (Py) is introduced at the meso­position of the asymmetric Cy7 with intramolecular charge transfer (ICT) to construct an atypical electron-transfer triad, which reduces ΔES1-S0, circumvents rapid charge recombination, and simultaneously enhances intersystem crossing (ISC) based on spin-orbit charge-transfer ISC (SOCT-ISC) mechanism. This unique molecular construction produces anti-Stokes luminescence (ASL) because the rotatable CN bond enriched in high vibrational-rotational energy levels improves hot-band absorption (HBA) efficiency. The obtained triad exhibits higher singlet oxygen quantum yield and photothermal conversion efficiency compared to indocyanine green (ICG) under irradiation above 800 nm. Cationization with Py enables the triad to target bacteria via intense electrostatic attractions, as well as biocidal property against a broad spectrum of bacteria in the dark. Moreover, the triad under irradiation can enhance biofilm eradication performance in vitro and statistically improve healing efficacy of MRSA-infected wound in mice. Thus, this work provides a simple but effective strategy to design small-molecule photosensitizers for synergistic phototherapy of bacterial infections. STATEMENT OF SIGNIFICANCE: We developed an orthogonal molecular cationization strategy to enhance the reactive oxygen species and thermal effects of heptamethine cyanine (Cy7) for photodynamic and photothermal treatments of bacterial infections. Specifically, cationic pyridine (Py) was introduced at the meso­position of the asymmetric Cy7 to construct an atypical electron-transfer triad, which reduced ΔES1-S0, circumvented rapid charge recombination, and simultaneously enhanced intersystem crossing (ISC). This triad, with a rotatable CN bond, produced anti-Stokes luminescence due to hot-band absorption. The triad enhanced antimicrobial performance and statistically improved the healing efficacy of MRSA-infected wounds in mice. This site-specific cationization strategy may provide insights into the design of small molecule-based photosensitizers for synergistic phototherapy of bacterial infections.

Asunto(s)

Infecciones Bacterianas , Fotoquimioterapia , Animales , Ratones , Fármacos Fotosensibilizantes/química , Especies Reactivas de Oxígeno , Fototerapia , Colorantes , Infecciones Bacterianas/tratamiento farmacológico , Piridinas/farmacología

RESUMEN

Synergistic photothermal immunotherapy has attracted widespread attention due to the mutually reinforcing therapeutic effects on primary and metastatic tumors. However, the lack of clinical approval nanomedicines for spatial, temporal, and dosage control of drug co-administration underscores the challenges facing this field. Here, a photothermal agent (Cy7-TCF) and an immune checkpoint blocker (NLG919) are conjugated via disulfide bond to construct a tumor-specific small molecule prodrug (Cy7-TCF-SS-NLG), which self-assembles into prodrug-like nano-assemblies (PNAs) that are self-delivering and self-formulating. In tumor cells, over-produced GSH cleaves disulfide bonds to release Cy7-TCF-OH, which re-assembles into nanoparticles to enhance photothermal conversion while generate reactive oxygen species (ROSs) upon laser irradiation, and then binds to endogenous albumin to activate near-infrared fluorescence, enabling multimodal imaging-guided phototherapy for primary tumor ablation and subsequent release of tumor-associated antigens (TAAs). These TAAs, in combination with the co-released NLG919, effectively activated effector T cells and suppressed Tregs, thereby boosting antitumor immunity to prevent tumor metastasis. This work provides a simple yet effective strategy that integrates the supramolecular dynamics and reversibility with stimuli-responsive covalent bonding to design a simple small molecule with synergistic multimodal imaging-guided phototherapy and immunotherapy cascades for cancer treatment with high clinical value.

Asunto(s)

Nanopartículas , Neoplasias , Profármacos , Humanos , Profármacos/uso terapéutico , Nanomedicina Teranóstica , Neoplasias/terapia , Fototerapia , Nanopartículas/química , Antígenos de Neoplasias , Inmunoterapia , Disulfuros , Línea Celular Tumoral

RESUMEN

Near-infrared (NIR) laser-induced photoimmunotherapy has aroused great interest due to its intrinsic noninvasiveness and spatiotemporal precision, while immune evasion evoked by lactic acid (LA) accumulation severely limits its clinical outcomes. Although several metabolic interventions have been devoted to ameliorate immunosuppression, intracellular residual LA still remains a potential energy source for oncocyte proliferation. Herein, an immunomodulatory nanoadjuvant based on a yolk-shell CoP/NiCoP (CNCP) heterostructure loaded with the monocarboxylate transporter 4 inhibitor fluvastatin sodium (Flu) is constructed to concurrently relieve immunosuppression and elicit robust antitumor immunity. Under NIR irradiation, CNCP heterojunctions exhibit superior photothermal performance and photocatalytic production of reactive oxygen species and hydrogen. The continuous heat then facilitates Flu release to restrain LA exudation from tumor cells, whereas cumulative LA can be depleted as a hole scavenger to improve photocatalytic efficiency. Subsequently, potentiated photocatalytic therapy can not only initiate systematic immunoreaction, but also provoke severe mitochondrial dysfunction and disrupt the energy supply for heat shock protein synthesis, in turn realizing mild photothermal therapy. Consequently, LA metabolic remodeling endows an intensive cascade treatment with an optimal safety profile to effectually suppress tumor proliferation and metastasis, which offers a new paradigm for the development of metabolism-regulated immunotherapy.

Asunto(s)

Nanopartículas , Neoplasias , Humanos , Fototerapia , Luz , Neoplasias/tratamiento farmacológico , Inmunoterapia , Lactatos/uso terapéutico , Línea Celular Tumoral , Nanopartículas/química

RESUMEN

The acceptance of nanoparticle technology in the quest for cancer treatment is due to its many potentials and possibilities of filling in the gaps in the limitations of the current treatment modalities. Insights into the possibilities of getting even more from this technology, as well as the synergistic properties of photothermal therapy (PTT) and photodynamic therapy (PDT)-the use of reactive oxygen species (ROS)-can also be exploited in the ablation of prostate cancer tumors. Therefore, the combination of gold and selenium photoactive nanoparticles as platforms for drug delivery via PTT/PDT in prostate cancer therapy, with a specific emphasis on the 'micro-carrier' based approach, was discussed and explored in this review under relevant subtopics ranging from understanding the complex chemistry and biology of the pharmacologically active Se/Au-containing agents to giving a thorough knowledge of these therapeutic agents' potential as a targeted and successful treatment strategy for prostate cancer by investigating the complex mechanisms behind their delivery, activation, and synergistic effects. Furthermore, this article presents a comprehensive overview of the current research environment, problems encountered, and future perspectives in the continuous war against prostate cancer.

RESUMEN

Background: Cancer stem cells (CSCs) are the most challenging issue in cancer treatment, because of their high resistance mechanisms, that can cause tumor recurrence after common cancer treatments such as drug and radiation based therapies, and the insufficient efficiency of common treatments in CSCs removal and the recurrence of tumors after these treatments, it is essential to consider other methods, including non-ionizing treatments likes light-based treatments and magnetic hyperthermia (MHT). Method and material: After synthesis, characterization and investigation, the toxicity of novel on A375 and MAD-MB-231 cell lines, magnetic hyperthermia and light-based treatments were applied. MTT assay and flow cytometry was employed to determine cell survival. the influence of combination therapy on CD44 + CD24-and CD133 + CD44+ cell population, Comparison and evaluation of combination treatments was done respectively using Combination Indices (CIs). Result: The final nanoparticle has a high efficiency in producing hydroxyl radicals and generating heat in MHT. According to CIs, we can conclude that combined using of light-based treatment and MHT in the presence of final synthesized nanoparticle have synergistic effect and a high ability to reduce the population of stem cells in both cell lines compared to single treatments. Conclusion: In this study a novel multi-functional nanoplatform acted well in dual and triple combined treatments, and showed a good performance in the eradication of CSCs, in A375 and MAD-MB-231 cell lines.

RESUMEN

Nanotechnology, an emerging and promising therapeutic tool, may improve the effectiveness of phototherapy (PT) in antitumor therapy because of the development of nanomaterials (NMs) with light-absorbing properties. The tumor-targeted PTs, such as photothermal therapy (PTT) and photodynamic therapy (PDT), transform light energy into heat and produce reactive oxygen species (ROS) that accumulate at the tumor site. The increase in ROS levels induces oxidative stress (OS) during carcinogenesis and disease development. Because of the localized surface plasmon resonance (LSPR) feature of copper (Cu), a vital trace element in the human body, Cu-based NMs can exhibit good near-infrared (NIR) absorption and excellent photothermal properties. In the tumor microenvironment (TME), Cu2+ combines with H2O2 to produce O2 that is reduced to Cu1+ by glutathione (GSH), causing a Fenton-like reaction that reduces tumor hypoxia and simultaneously generates ROS to eliminate tumor cells in conjunction with PTT/PDT. Compared with other therapeutic modalities, PTT/PDT can precisely target tumor location to kill tumor cells. Moreover, multiple treatment modalities can be combined with PTT/PDT to treat a tumor using Cu-based NMs. Herein, we reviewed and briefly summarized the mechanisms of actions of tumor-targeted PTT/PDT and the role of Cu, generated from Cu-based NMs, in PTs. Furthermore, we described the Cu-based NMs used in PTT/PDT applications.

RESUMEN

The attenuation of bacterial metabolism provides an adjunct to the treatment of bacterial infections. To develop a bacterial eradication agent, a bioactivatable material (BP@Eu-TCPP) was designed and synthesized by coordination and reduction of europium(III) with thin-layer black phosphorus (BP) and tetrakis (4-carboxyphenyl) porphyrin (TCPP). The existence of the P-Eu bond and Eu2+ 3d5/2 in X-ray photoelectron spectroscopy confirmed the successful synthesis of BP@Eu-TCPP. This material showed high fluorescence sensitivity to l-Arginine (l-Arg) and the main binding ratio of BP@Eu-TCPP to l-Arg was ca. 1:2 or 1:3, with the limit of detection of 4.0 µM. The material also showed good photothermal properties and stability, with a photothermal conversion efficiency of 37.3%. Although metal coordination has blocked the generation of 1O2, the addition of l-Arg to BP@Eu-TCPP can restore 1O2 generation upon red light-emitting diode (LED) light irradiation due to the formation of water-soluble Arg-TCPP species. Additionally, BP@Eu-TCPP was enabled to change the bacterial membrane and interfered with the bacterial iron absorption that effectively contributes to bacterial eradication. Such BP@Eu-TCPP is promised to be a novel material for the detection of l-Arg and l-Arg-activated photodynamic therapy.

Asunto(s)

Europio , Porfirinas , Arginina , Tiempo de Tromboplastina Parcial , Fósforo

RESUMEN

BACKGROUND: Osteosarcoma (OS) is the most prevalent primary malignant bone tumor. However, single-agent chemotherapy exhibits limited efficacy against OS and often encounters tumor resistance. Therefore, we designed and constructed an integrated treatment strategy of photothermal therapy (PTT) combined with chemotherapy and used a surface-encapsulated platelet-osteosarcoma hybrid membrane (OPM) that enhances circulation time and enables OS-specific targeting. RESULTS: The OPM functions as a shell structure, encapsulating multiple drug-loaded nanocores (BPQDs-DOX) and controlling the release rate of doxorubicin (DOX). Moreover, near-infrared light irradiation accelerates the release of DOX, thereby extending circulation time and enabling photostimulation-responsive release. The OPM encapsulation system improves the stability of BPQDs, enhances their photothermal conversion efficiency, and augments PTT efficacy. In vitro and ex vivo experiments demonstrate that BPQDs-DOX@OPM effectively delivers drugs to tumor sites with prolonged circulation time and specific targeting, resulting in superior anti-tumor activity compared to single-agent chemotherapy. Furthermore, these experiments confirm the favorable biosafety profile of BPQDs-DOX@OPM. CONCLUSIONS: Compared to single-agent chemotherapy, the combined therapy using BPQDs-DOX@OPM offers prolonged circulation time, targeted drug delivery, enhanced anti-tumor activity, and high biosafety, thereby introducing a novel approach for the clinical treatment of OS.

Asunto(s)

Neoplasias Óseas , Nanopartículas , Osteosarcoma , Puntos Cuánticos , Humanos , Puntos Cuánticos/química , Fósforo/química , Doxorrubicina/farmacología , Doxorrubicina/química , Fototerapia/métodos , Osteosarcoma/tratamiento farmacológico , Neoplasias Óseas/tratamiento farmacológico , Línea Celular Tumoral , Nanopartículas/química

RESUMEN

Cancer is considered a major societal challenge for the next decade worldwide. Developing strategies for simultaneous diagnosis and treatment has been considered a promising tool for fighting cancer. For this, the development of nanomaterials incorporating prototypic near-infrared (NIR)-light responsive probes, such as heptamethine cyanines, has been showing very promising results. The heptamethine cyanine-incorporating nanomaterials can be used for a tumor's visualization and, upon interaction with NIR light, can also produce a photothermal/photodynamic effect with a high spatio-temporal resolution and minimal side effects, leading to an improved therapeutic outcome. In this work, we studied the interaction of 12 NIR-light responsive probes with lipid membrane models by molecular dynamics simulations. We performed a detailed characterization of the location, orientation, and local perturbation effects of these molecules on the lipid bilayer. Based on this information, the probes were divided into two groups, predicting a lower and higher perturbation of the lipid bilayer. From each group, one molecule was selected for testing in a membrane leakage assay. The experimental data validate the hypothesis that molecules with charged substituents, which function as two polar anchors for the aqueous phase while spanning the membrane thickness, are more likely to disturb the membrane by the formation of defects and pores, increasing the membrane leakage. The obtained results are expected to contribute to the selection of the most suitable molecules for the desired application or eventually guiding the design of probe modifications for achieving an optimal interaction with tumor cell membranes.