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1.
Artículo en Inglés | MEDLINE | ID: mdl-39141571

RESUMEN

BACKGROUND: Oral delivery of small interfering RNAs (siRNAs) draws significant attention, but the gastrointestinal tract (GIT) has many biological barriers that limit the drugs' bioavailability. The aim of this work was to investigate the potential of nano- and micron-sized CaCO3 and PLA carriers for oral delivery of siRNA and reveal a relationship between the physicochemical features of these carriers and their biodistribution. RESEARCH DESIGN AND METHODS: In vitro stability of carriers was investigated in simulated gastric and intestinal fluids. Toxicity and cellular uptake were investigated on Caco-2 cells. The biodistribution profiles of the developed CaCO3 and PLA carriers were examined using different visualization methods, including SPECT, fluorescence imaging, radiometry, and histological analysis. The delivery efficiency of siRNA loaded carriers was investigated both in vitro and in vivo. RESULTS: Micro-sized carriers were accumulated in the stomach and later localized in the colon tissues. The nanoscale particles (100-250 nm) were distributed in the colon tissues. nPLA was also detected in small intestine. The developed carriers can prevent siRNA from premature degradation in GIT media. CONCLUSION: Our results reveal how the physicochemical properties of the particles, including their size and material type can affect their biodistribution profile and oral delivery of siRNA.

2.
Biomater Sci ; 12(13): 3431-3445, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38812410

RESUMEN

Although small molecule drugs are widely used in chemotherapy, their low bioavailability, low-concentrated dose in the tumor zone, systemic toxicity, and chemoresistance can significantly limit the therapeutic outcome. These drawbacks can be overcome by two main strategies: (i) development of novel therapeutic molecules with more significant antitumor activity than currently available drugs and (ii) loading chemotherapeutic agents into drug delivery systems. In this study, we aimed to encapsulate a highly prospective small molecule drug based on substituted 2-aminothiophene (2-AT) into calcium carbonate (CaCO3) microparticles (MPs) for the treatment of melanoma tumors. In particular, we have optimized the encapsulation of 2-AT into MPs (2-AT@MPs), studied drug release efficiency, investigated cellular uptake, and evaluated in vivo biodistribution and tumor inhibition efficiency. In vitro results revealed that 2-AT@MPs were able to penetrate into tumor spheroids, leading to prolonged release of 2-AT. By performing intratumoral injection of 2-AT@MPs we observed significant melanoma suppressions in murine models: ∼0.084 cm3 for 2-AT@MPs at a dose of 0.4 g kg-1versus ∼1.370 cm3 for untreated mice. In addition, the 2-AT@MPs showed negligible in vivo toxicity towards major organs such as heart, lung, liver, kidney, and spleen. Thus, this work provided an efficient strategy for the improved chemotherapy of solid tumors by using an encapsulated form of small molecule drugs.


Asunto(s)
Antineoplásicos , Carbonato de Calcio , Portadores de Fármacos , Melanoma , Tiofenos , Animales , Carbonato de Calcio/química , Carbonato de Calcio/administración & dosificación , Ratones , Tiofenos/química , Tiofenos/administración & dosificación , Tiofenos/farmacología , Tiofenos/farmacocinética , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/administración & dosificación , Portadores de Fármacos/química , Melanoma/tratamiento farmacológico , Melanoma/patología , Línea Celular Tumoral , Liberación de Fármacos , Distribución Tisular , Humanos , Melanoma Experimental/tratamiento farmacológico , Melanoma Experimental/patología , Ratones Endogámicos C57BL
3.
Bioorg Chem ; 148: 107468, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38781670

RESUMEN

A new efficient and versatile one-pot three-component synthesis of substituted pyrrolo[1,2-a]thieno[3,2-e]pyrimidine derivatives has been developed. It is based on a multistep cascade reaction from 2-aminothiophenes and 2-hydroxy-4-oxobut-2-enoic acids, and derivatives of cyanoacetic acid catalyzed by diisopropylethylamine. As a result, novel pyrrolo[1,2-a]thieno[3,2-e]pyrimidine derivatives (21 compounds) were synthesized in a mild reaction conditions with a high yield. The structures of the developed compounds were confirmed by NMR and elemental analysis. The influence of electron-withdrawing or electron-donor substituents on the antitumor activity of the developed compounds has been identified. In vitro screening analysis of 21 compounds revealed six lead candidates (12aa, 12dc, 12hc, 12ic, 12lb, and 12mb) that demonstrated the most significant antitumor activity against B16-F10, 4T1 and CT26 cells. Necrosis/apoptosis assay showed that apoptosis was the predominant mechanism of cell death. Molecular docking analysis revealed several potential targets for tested compounds, i.e. phosphatidylinositol 5-phosphate 4-kinase (PI5P4K2C), proto-oncogene serine/threonine-protein kinase (Pim-1), nicotinamide phosphoribosyltransferase (NAMPT) and dihydrofolate reductase (DHFR). The lead compound (12aa) can effectively induce cell apoptosis, possesses a high yield (98 %) and requires low-cost starting chemicals for its synthesis. In vivo experiments with melanoma-bearing mice confirmed that 12aa compound resulted in the significant tumor inhibition on 15 d after the therapy. In particular, tumor volume was ∼0.19 cm3 for 50 mg/kg versus ∼2.39 cm3 in case of untreated mice and tumor weight was ∼71.6 mg for 50 mg/kg versus ∼452.4 mg when considered untreated mice. Thus, our results demonstrated the high potential of the 12aa compound in the treatment of melanoma and can be recommended for further preclinical studies.


Asunto(s)
Antineoplásicos , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Pirimidinas , Pirroles , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Animales , Pirimidinas/química , Pirimidinas/síntesis química , Pirimidinas/farmacología , Ratones , Relación Estructura-Actividad , Estructura Molecular , Humanos , Pirroles/química , Pirroles/farmacología , Pirroles/síntesis química , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Línea Celular Tumoral , Simulación del Acoplamiento Molecular , Proto-Oncogenes Mas , Apoptosis/efectos de los fármacos , Ratones Endogámicos C57BL , Melanoma Experimental/tratamiento farmacológico , Melanoma Experimental/patología , Melanoma Experimental/metabolismo
4.
Nanomedicine ; 59: 102753, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38734039

RESUMEN

In this study, we have considered four types of nanoparticles (NPs): polylactic acid (PLA), gold (Au), calcium carbonate (CaCO3), and silica (SiO2) with similar sizes (TEM: 50-110 nm and DLS: 110-140 nm) to examine their passive accumulation in three different tumors: colon (CT26), melanoma (B16-F10), and breast (4T1) cancers. Our results demonstrate that each tumor model showed a different accumulation of NPs, in the following order: CT26 > B16-F10 > 4T1. The Au and PLA NPs were evidently characterized by a higher delivery efficiency in case of CT26 tumors compared to CaCO3 and SiO2 NPs. The Au NPs demonstrated the highest accumulation in B16-F10 cells compared to other NPs. These results were verified using SPECT, ex vivo fluorescence bioimaging, direct radiometry and histological analysis. Thus, this work contributes to new knowledge in passive tumor targeting of NPs and can be used for the development of new strategies for delivery of bioactive compounds.


Asunto(s)
Oro , Nanopartículas , Animales , Ratones , Nanopartículas/química , Oro/química , Dióxido de Silicio/química , Poliésteres/química , Portadores de Fármacos/química , Línea Celular Tumoral , Carbonato de Calcio/química , Femenino , Humanos , Sistemas de Liberación de Medicamentos , Ratones Endogámicos BALB C , Melanoma Experimental/patología , Melanoma Experimental/metabolismo , Melanoma Experimental/tratamiento farmacológico , Neoplasias del Colon/patología , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/metabolismo
6.
J Mater Chem B ; 12(17): 4232-4247, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38601990

RESUMEN

The design and synthesis of nano- and microcarriers for preclinical and clinical imaging are highly attractive due to their unique features, for example, multimodal properties. However, broad translation of these carriers into clinical practice is postponed due to the unknown biological reactivity of the new components used for their synthesis. Here, we have developed microcarriers (∼2-3 µm) and  nanocarriers (<200 nm) made of barium carbonate (BaCO3) for multiple imaging applications in vivo. In general, barium in the developed carriers can be used for X-ray computed tomography, and the introduction of a diagnostic isotope (99mTc) into the BaCO3 structure enables in vivo visualization using single-photon emission computed tomography. The bioimaging has shown that the radiolabeled BaCO3 nano- and microcarriers had different biodistribution profiles and tumor accumulation efficiencies after intratumoral and intravenous injections. In particular, in the case of intratumoral injection, all the types of used carriers mostly remained in the tumors (>97%). For intravenous injection, BaCO3 microcarriers were mainly localized in the lung tissues. However, BaCO3 NPs were mainly accumulated in the liver. These results were supported by ex vivo fluorescence imaging, direct radiometry, and histological analysis. The BaCO3-based micro- and nanocarriers showed negligible in vivo toxicity towards major organs such as the heart, lungs, liver, kidneys, and spleen. This study provides a simple strategy for the design and fabrication of the BaCO3-based carriers for the development of dual bioimaging.


Asunto(s)
Bario , Carbonatos , Tomografía Computarizada de Emisión de Fotón Único , Animales , Ratones , Carbonatos/química , Bario/química , Tomografía Computarizada por Rayos X , Tamaño de la Partícula , Nanopartículas/química , Humanos , Distribución Tisular
8.
ACS Biomater Sci Eng ; 10(4): 2324-2336, 2024 04 08.
Artículo en Inglés | MEDLINE | ID: mdl-38520335

RESUMEN

Many methods for cancer treatment have been developed. Among them photothermal therapy (PTT) has drawn the most significant attention due to its noninvasiveness, remote control activation, and low side effects. However, a limited depth of light penetration of PTT is the main drawback. To improve the therapeutic efficiency, the development of combined PTT with other therapeutic agents is highly desirable. In this work, we have designed multifunctional composite carriers based on polylactic acid (PLA) particles decorated with gold nanorods (Au NRs) as nanoheaters and selenium nanoparticles (Se NPs) for reactive oxygen species (ROS) production in order to perform a combined PTT against B16-F10 melanoma. To do this, we have optimized the synthesis of PLA particles modified with Se NPs and Au NRs (PLA-Se:Au), studied the cellular interactions of PLA particles with B16-F10 cells, and analyzed in vivo biodistribution and tumor inhibition efficiency. The results of in vitro and in vivo experiments demonstrated the synergistic effect from ROS induced by Se NPs and the heating from Au NRs. In melanoma tumor-bearing mice, intratumoral injection of PLA-Se:Au followed by laser irradiation leads to almost complete elimination of tumor tissues. Thus, the optimal photothermal properties and ROS-generating capacity allow us to recommend PLA-Se:Au as a promising candidate for the development of the combined PTT against melanoma.


Asunto(s)
Hipertermia Inducida , Melanoma , Nanopartículas del Metal , Animales , Ratones , Melanoma/terapia , Especies Reactivas de Oxígeno , Distribución Tisular , Nanopartículas del Metal/uso terapéutico , Poliésteres
9.
Biomater Sci ; 12(2): 453-467, 2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38059526

RESUMEN

The size of drug carriers strongly affects their biodistribution, tissue penetration, and cellular uptake in vivo. As a result, when such carriers are loaded with therapeutic compounds, their size can influence the treatment outcomes. For internal α-radionuclide therapy, the carrier size is particularly important, because short-range α-emitters should be delivered to tumor volumes at a high dose rate without any side effects, i.e. off-target irradiation and toxicity. In this work, we aim to evaluate and compare the therapeutic efficiency of calcium carbonate (CaCO3) microparticles (MPs, >2 µm) and nanoparticles (NPs, <100 nm) labeled with radium-223 (223Ra) for internal α-radionuclide therapy against 4T1 breast cancer. To do this, we comprehensively study the internalization and penetration efficiency of these MPs and NPs, using 2D and 3D cell cultures. For further therapeutic tests, we develop and modify a chelator-free method for radiolabeling of CaCO3 MPs and NPs with 223Ra, improving their radiolabeling efficiency (>97%) and radiochemical stability (>97%). After intratumoral injection of 223Ra-labeled MPs and NPs, we demonstrate their different therapeutic efficiencies against a 4T1 tumor. In particular, 223Ra-labeled NPs show a tumor inhibition of approximately 85%, which is higher compared to 60% for 223Ra-labeled MPs. As a result, we can conclude that 223Ra-labeled NPs have a more suitable biodistribution within 4T1 tumors compared to 223Ra-labeled MPs. Thus, our study reveals that 223Ra-labeled CaCO3 NPs are highly promising for internal α-radionuclide therapy.


Asunto(s)
Neoplasias de la Mama , Nanopartículas , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/patología , Carbonato de Calcio/química , Distribución Tisular , Portadores de Fármacos/química , Nanopartículas/química , Radioisótopos/uso terapéutico
10.
J Phys Chem Lett ; 15(1): 113-120, 2024 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-38147530

RESUMEN

Although chirality plays an important role in the natural world, it has also attracted much scientific attention in nanotechnology, in particular, spintronics and bioapplications. Chiral carbon dots (CDs) are promising nanoparticles for sensing and bioimaging since they are biocompatible, ecofriendly, and free from toxic elements. Herein, green and red emissive chiral CDs are fabricated via surface modification treatment of achiral CDs at room temperature. After modification with l-cysteine molecules, the treated CDs demonstrate an intense chiral signal in the region of 200-300 nm with a dissymmetry factor up to 2.3 × 10-4 and high photoluminescence quantum yields of 19% and 15% for green and red emission bands, respectively. These CDs preserve their chiral signal in different ion systems, such as those with pH changes or in the presence of metal ions, along with remarkably low cytotoxicity, making them potential candidates for use as photoluminescent labels for biological objects.


Asunto(s)
Nanopartículas , Puntos Cuánticos , Cisteína , Carbono/química , Puntos Cuánticos/química , Iones
11.
Nano Lett ; 23(23): 10811-10820, 2023 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-37988557

RESUMEN

Redox-responsive drug delivery systems present a promising avenue for drug delivery due to their ability to leverage the unique redox environment within tumor cells. In this work, we describe a facile and cost-effective one-pot synthesis method for a redox-responsive delivery system based on novel trithiocyanuric acid (TTCA) nanoparticles (NPs). We conduct a thorough investigation of the impact of various synthesis parameters on the morphology, stability, and loading capacity of these NPs. The great drug delivery potential of the system is further demonstrated in vitro and in vivo by using doxorubicin as a model drug. The developed TTCA-PEG NPs show great drug delivery efficiency with minimal toxicity on their own both in vivo and in vitro. The simplicity of this synthesis, along with the promising characteristics of TTCA-PEG NPs, paves the way for new opportunities in the further development of redox-responsive drug delivery systems based on TTCA.


Asunto(s)
Sistemas de Liberación de Medicamentos , Nanopartículas , Sistemas de Liberación de Medicamentos/métodos , Doxorrubicina/uso terapéutico , Oxidación-Reducción , Portadores de Fármacos
13.
ACS Appl Mater Interfaces ; 15(40): 47541-47551, 2023 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-37773641

RESUMEN

Laser conversion of metal-organic frameworks (MOFs) has recently emerged as a fast and low-energy consumptive approach to create scalable MOF derivatives for catalysis, energy, and optics. However, due to the virtually unlimited MOF structures and tunable laser parameters, the results of their interaction are unpredictable and poorly controlled. Here, we experimentally base a general approach to create nano- to centimeter-scale MOF derivatives with the desired nonlinear optical and catalytic properties. Five three- and two-dimensional MOFs, differing in chemical composition, topology, and thermal resistance, have been selected as precursors. Tuning the laser parameters (i.e., pulse duration from fs to ns and repetition rate from kHz to MHz), we switch between ultrafast nonthermal destruction and thermal decomposition of MOFs. We have established that regardless of the chemical composition and MOF topology, the tuning of the laser parameters allows obtaining a series of structurally different derivatives, and the transition from femtosecond to nanosecond laser regimes ensures the scaling of the derivatives from nano- to centimeter scales. Herein, the thermal resistance of MOFs affects the structure and chemical composition of the resulting derivatives. Finally, we outline the "laser parameters versus MOF structure" space, in which one can create the desired and scalable platforms with nonlinear optical properties from photoluminescence to light control and enhanced catalytic activity.

15.
Adv Healthc Mater ; 12(24): e2300652, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37306377

RESUMEN

Current applications of multifunctional nanozymes for reprogramming the redox homeostasis of the tumor microenvironment (TME) have been severely confronted with low catalytic activity and the ambiguity of active sites of nanozymes, as well as the stress resistance from the rigorous physical environment of tumor cells. Herein, the Sm/Co-doped mesoporous silica with 3PO-loaded nanozymes (denoted as mSC-3PO) are rationally constructed for simultaneously inhibiting energy production by adenosine triphosphate (ATP) inhibitor 3PO and reprogramming TME by multiactivities of nanozymes with photothermal effect assist, i.e., enhanced peroxidase-like, catalase-like activity, and glutathione peroxidase-like activities, facilitating reactive oxygen species (ROS) generation, promoting oxygen content, and restraining the over-expressed glutathione. Through the optimal regulation of nanometric size and doping ratio, the fabricated superparamagnetic mSC-3PO enables the excellent exposure of active sites and avoids agglomeration owing to the large specific surface and mesoporous structure, thus providing adequate Sm/Co-doped active sites and enough spatial distribution. The constructed Sm/Co centers both participate in the simulated biological enzyme reactions and carry out the double-center catalytic process (Sm3+ and Co3+ /Co2+ ). Significantly, as the inhibitor of glycolysis, 3PO can reduce the ATP flow by cutting down the energy transform, thereby inhibiting tumor angiogenesis and assisting ROS to promote the early withering of tumor cells. In addition, the considerable near-infrared (NIR) light absorption of mSC-3PO can adapt to NIR excitable photothermal treatment therapy and photoexcitation-promoted enzymatic reactions. Taken together, this work presents a typical therapeutic paradigm of multifunctional nanozymes that simultaneously reprograms TME and promotes tumor cell apoptosis with photothermal assistance.


Asunto(s)
Neoplasias , Microambiente Tumoral , Humanos , Especies Reactivas de Oxígeno , Adenosina Trifosfato , Catálisis , Glutatión , Neoplasias/terapia , Peróxido de Hidrógeno
16.
J Control Release ; 359: 400-414, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37315692

RESUMEN

The use of nanoparticles (NPs) as delivery vehicles for multiple drugs is an intensively developing area. However, the success of NPs' accumulation in the tumor area for efficient tumor treatment has been recently questioned. Distribution of NPs in a laboratory animal is mainly related to the administration route of NPs and their physicochemical parameters, which significantly affect the delivery efficiency. In this work, we aim to compare the therapeutic efficiency and side effects of the delivery of multiple therapeutic agents with NPs by both intravenous and intratumoral injections. For this, we systematically developed universal nanosized carriers based on calcium carbonate (CaCO3) NPs (< 100 nm) that were co-loaded with a photosensitizer (Chlorin e6, Ce6) and chemotherapeutic agent (doxorubicin, Dox) for combined chemo- and photodynamic therapy (PDT) of B16-F10 melanoma tumors. By performing intratumoral or intravenous injections of NPs, we observed different biodistribution profiles and tumor accumulation efficiencies. In particular, after intratumoral administration of NPs, they mostly remained in the tumors (> 97%); while for intravenous injection, the tumor accumulation of NPs was determined to be 8.67-12.4 ID/g%. Although the delivery efficiency of NPs (presented in ID/g%) in the tumor differs, we have developed an effective strategy for tumor inhibition based on combined chemo- and PDT by both intratumoral and intravenous injections of NPs. Notably, after the combined chemo- and PDT treatment with Ce6/Dox@CaCO3 NPs, all B16-F10 melanoma tumors in mice shrank substantially, by approximately 94% for intratumoral injection and 71% for intravenous injection, which are higher values compared to mono-therapy. In addition, the CaCO3 NPs showed negligible in vivo toxicity towards major organs such as the heart, lungs, liver, kidneys, and spleen. Thus, this work demonstrates a successful approach for the enhancement of NPs' efficiency in combined anti-tumor therapy.


Asunto(s)
Melanoma , Nanopartículas , Fotoquimioterapia , Porfirinas , Animales , Ratones , Distribución Tisular , Fármacos Fotosensibilizantes/uso terapéutico , Fármacos Fotosensibilizantes/farmacología , Doxorrubicina/uso terapéutico , Doxorrubicina/farmacología , Nanopartículas/uso terapéutico , Melanoma/tratamiento farmacológico , Línea Celular Tumoral , Porfirinas/farmacología
17.
Eur J Med Chem ; 254: 115325, 2023 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-37084598

RESUMEN

The design and synthesis of new promising compounds based on thienopyrimidine scaffold containing 2-aminothiophene fragments with good safety and favorable drug-like properties are highly relevant for chemotherapy. In this study, a series of 14 variants of thieno[3,2-e]pyrrolo[1,2-a]pyrimidine derivatives (11aa-oa) and their precursors (31 compounds) containing 2-aminothiophenes fragments (9aa-mb, 10aa-oa) were synthesized and screened for their cytotoxicity against B16-F10 melanoma cells. The selectivity of the developed compounds was assessed by determining the cytotoxicity using normal mouse embryonic fibroblasts (MEF NF2 cells). The lead compounds 9cb, 10ic and 11jc with the most significant antitumor activity and minimum cytotoxicity on normal non-cancerous cells were chosen for further in vivo experiments. Additional in vitro experiments with compounds 9cb, 10ic and 11jc showed that apoptosis was the predominant mechanism of death in B16-F10 melanoma cells. With support from in vivo studies, compounds 9cb, 10ic and 11jc demonstrated the biosafety to healthy mice and significant inhibition of the metastatic nodules in pulmonary metastatic melanoma mouse model. Histological analysis detected no abnormal changes in the main organs (the liver, spleen, kidneys, and heart) after the therapy. Thus, the developed compounds 9cb, 10ic and 11jc demonstrate high efficiency in the treatment of pulmonary metastatic melanoma and can be recommended for further preclinical investigation of the melanoma treatment.


Asunto(s)
Antineoplásicos , Melanoma Experimental , Animales , Ratones , Fibroblastos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Melanoma Experimental/tratamiento farmacológico , Pulmón , Pirimidinas/farmacología , Pirimidinas/uso terapéutico
18.
J Colloid Interface Sci ; 643: 232-246, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37060699

RESUMEN

Recently, multi-modal combined photothermal therapy (PTT) with the use of photo-active materials has attracted significant attention for cancer treatment. However, drug carriers enabling efficient heating at the tumor site are yet to be designed: this is a fundamental requirement for broad implementation of PTT in clinics. In this work, we design and develop hybrid carriers based on multilayer capsules integrated with selenium nanoparticles (Se NPs) and gold nanorods (Au NRs) to realize reactive oxygen species (ROS)-mediated combined PTT. We show theoretically and experimentally that cooperative interaction of Se NPs with Au NRs improves the heat release efficiency of the developed capsules. In addition, after uptake by tumor cells, intracellular ROS level amplified by Se NPs inhibits the tumor growth. As a consequence, the synergy between Se NPs and Au NRs exhibits the advantages of hybrid carriers such as (i) improved photothermal conversion efficiency and (ii) dual-therapeutic effect. The results of in vitro and in vivo experiments demonstrate that the combination of ROS-mediated therapy and PTT has a higher tumor inhibition efficiency compared to the single-agent treatment (using only Se-loaded or Au-loaded capsules). Furthermore, the developed hybrid carriers show negligible in vivo toxicity towards major organs such as the heart, lungs, liver, kidneys and spleen. This study not only provides a potential strategy for the design of multifunctional "all-in-one" carriers, but also contributes to the development of combined PTT in clinical practice.


Asunto(s)
Neoplasias , Fotoquimioterapia , Selenio , Humanos , Fotoquimioterapia/métodos , Oro/farmacología , Selenio/farmacología , Especies Reactivas de Oxígeno , Polímeros , Proyectos de Investigación , Terapia Fototérmica , Neoplasias/terapia , Línea Celular Tumoral
19.
ACS Appl Mater Interfaces ; 15(10): 13460-13471, 2023 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-36867432

RESUMEN

Conventional cancer therapy methods have serious drawbacks that are related to the nonspecific action of anticancer drugs that leads to high toxicity on normal cells and increases the risk of cancer recurrence. The therapeutic effect can be significantly enhanced when various treatment modalities are implemented. Here, we demonstrate that the radio- and photothermal therapy (PTT) delivered through nanocarriers (gold nanorods, Au NRs) in combination with chemotherapy in a melanoma cancer results in complete tumor inhibition compared to the single therapy. The synthesized nanocarriers can be effectively labeled with 188Re therapeutic radionuclide with a high radiolabeling efficiency (94-98%) and radiochemical stability (>95%) that are appropriate for radionuclide therapy. Further, 188Re-Au NRs, mediating the conversion of laser radiation into heat, were intratumorally injected and PTT was applied. Upon the irradiation of a near-infrared laser, dual photothermal and radionuclide therapy was achieved. Additionally, the combination of 188Re-labeled Au NRs with paclitaxel (PTX) has significantly improved the treatment efficiency (188Re-labeled Au NRs, laser irradiation, and PTX) compared to therapy in monoregime. Thus, this local triple-combination therapy can be a step toward the clinical translation of Au NRs for use in cancer treatment.


Asunto(s)
Antineoplásicos , Melanoma , Nanotubos , Humanos , Terapia Fototérmica , Antineoplásicos/farmacología , Fototerapia/métodos , Paclitaxel/farmacología , Paclitaxel/uso terapéutico , Melanoma/tratamiento farmacológico , Radioisótopos/uso terapéutico , Oro/farmacología , Línea Celular Tumoral
20.
ACS Nano ; 17(7): 6833-6848, 2023 04 11.
Artículo en Inglés | MEDLINE | ID: mdl-36974997

RESUMEN

Specific generation of reactive oxygen species (ROS) within tumors in situ catalyzed by nanozymes is a promising strategy for cancer therapeutics. However, it remains a significant challenge to fabricate highly efficient nanozymes acting in the tumor microenvironment. Herein, we develop a bimetallic nanozyme (Pt50Sn50) with the photothermal enhancement of dual enzymatic activities for tumor catalytic therapy. The structures and activities of PtSn bimetallic nanoclusters (BNCs) with different Sn content are explored and evaluated systematically. Experimental comparisons show that the Pt50Sn50 BNCs exhibit the highest activities among all those investigated, including enzymatic activity and photothermal property, due to the generation of SnO2-x with oxygen vacancy (Ovac) sites on the surface of Pt50Sn50 BNCs. Specifically, the Pt50Sn50 BNCs exhibit photothermal-enhanced peroxidase-like and catalase-like activities, as well as a significantly enhanced anticancer efficacy in both multicellular tumor spheroids and in vivo experiments. Due to the high X-ray attenuation coefficient and excellent light absorption property, the Pt50Sn50 BNCs also show dual-mode imaging capacity of computed tomography and photoacoustic imaging, which could achieve in vivo real-time monitoring of the therapeutic process. Therefore, this work will advance the development of noble-metal nanozymes with optimal composition for efficient tumor catalytic therapy.


Asunto(s)
Neoplasias , Humanos , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Especies Reactivas de Oxígeno , Catálisis , Oxígeno , Peroxidasa , Microambiente Tumoral , Línea Celular Tumoral , Peróxido de Hidrógeno
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