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1.
Colloids Surf B Biointerfaces ; 189: 110810, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32014651

RESUMO

In this study, a versatile doxorubicin (DOX)-loaded yolk-shell nano-particles (HMCMD) assembled with manganese dioxide (MnO2) as the core and copper sulfide (HMCuS) as the mesoporous (∼ 6.4 nm) shell, was designed and synthesized. The resulting HMCMD possess excellent photothermal conversion efficiency. The DOX release from the yolk-shell nanoparticles could be promoted by laser irradiation, which increased the chemotherapy of DOX. Meanwhile, Mn2+ could be released from the HMCMD through a redox reaction between MnO2 and abundant glutathione (GSH) in tumor cells. The released Mn2+ could promote the decomposition of the intracellular hydrogen peroxide (H2O2) by Fenton-like reaction to generate the highly toxic hydroxyl radicals (·OH), thus exhibiting the effective chemodynamic therapy (CDT). Additionally, the efficiency of Mn2+-mediated CDT could be effectively enhanced by NIR irradiation. Further modification of polyethylene glycol (PEG) would improve the water solubility of the HMCMD to promote the uptake by MCF-7 cells. Hence, the HMCMD with synergistic effects of chemotherapy and chemodynamic/photothermal therapy would provide an alternative strategy in antitumor research.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Glutationa/antagonistas & inibidores , Nanopartículas/química , Antibióticos Antineoplásicos/síntese química , Antibióticos Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Doxorrubicina/síntese química , Doxorrubicina/química , Liberação Controlada de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Glutationa/metabolismo , Humanos , Raios Infravermelhos , Células MCF-7 , Tamanho da Partícula , Propriedades de Superfície , Células Tumorais Cultivadas
2.
ACS Appl Mater Interfaces ; 12(2): 1963-1972, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31873002

RESUMO

Photodynamic therapy (PDT) as a noninvasive therapy mode has attracted considerable attention in the field of oncotherapy. However, the PDT efficacy is restricted either by the tumor hypoxia environment or the inherent properties of photosensitizers (PSs) including bad water solution, photobleaching, and easy aggregation. Herein, we designed and synthesized a new two-dimensional (2D) metal-organic framework, Sm-tetrakis(4-carboxyphenyl)porphyrin (TCPP) nanosheets, by assembling transition metal ions (Sm3+) and PSs (TCPP), on which the catalase (CAT)-mimicking platinum nanozymes were then in situ grown for sufficient oxygen supply during PDT. The prepared Sm-TCPP with nanoplate morphology (∼100 nm in diameter) and ultrathin thickness (<10 nm) showed significantly enhanced 1O2 generation capacity due to the improved physicochemical properties and the enhanced intersystem crossing from heavy Sm nodes. More importantly, the CAT-mimicking Pt nanozyme on the Sm-TCPP nanosheets could effectively convert over-expressed H2O2 in the tumor microenvironment into O2 to relieve tumor hypoxia. Further, the triphenylphosphine (TPP) molecule was introduced to Sm-TCPP-Pt to develop a mitochondrion-targeting and O2 self-supply PDT system. The in vitro and in vivo experimental results based on the MCF-7 breast cancer model revealed that Sm-TCPP-Pt/TPP could relieve tumor hypoxia and the generated reactive oxygen species nearby intracellular mitochondria significantly induced cell apoptosis. This study offers an engineering strategy to integrate 2D PS-based metal-organic frameworks and nanozymes into a nanoplatform to surmount the pitfalls of traditional PDT.


Assuntos
Materiais Biomiméticos/farmacologia , Catalase/metabolismo , Estruturas Metalorgânicas/farmacologia , Mitocôndrias/metabolismo , Nanopartículas/química , Oxigênio/farmacologia , Fotoquimioterapia , Platina/farmacologia , Antineoplásicos/farmacologia , Catálise , Humanos , Luz , Células MCF-7 , Nanopartículas/ultraestrutura , Porfirinas , Espécies Reativas de Oxigênio/metabolismo , Difração de Raios X
3.
Dalton Trans ; 48(45): 16861-16868, 2019 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-31710076

RESUMO

The efficiency of photosensitizers in tumor photodynamic therapy (PDT) often compromises their poor water solubility, low extinction coefficients, photobleaching, and dissatisfactory reactive oxygen species (ROS) generation efficiency. Herein, a nanoscale 2D metal-organic framework, Sm-H2TCPP nanosheets, was first synthesized by Sm3+-driven coordination with a porphyrin derivative (tetrakis(4-carboxyphenyl)porphyrin (H2TCPP)) for highly effective PDT of breast cancer. The prepared Sm-H2TCPP possessed nanoplate morphology with ultrathin thickness at the sub-10 nm level and an ultrasmall plane size at the sub-100 nm level. Compared with free H2TCPP, the prominent ROS generation capacity of the well-defined Sm-H2TCPP nanosheets is mainly attributed to their improved physicochemical properties and the enhanced intersystem crossing caused by heavy Sm nodes. The significantly improved PDT efficacy of the Sm-H2TCPP nanosheets was further investigated in vitro and in vivo based on the MCF-7 breast cancer model. It is envisaged that the Sm-H2TCPP nanosheets will offer a new avenue for the development of a new class of potential PDT agents.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Estruturas Metalorgânicas/farmacologia , Metaloporfirinas/farmacologia , Nanopartículas/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Células MCF-7 , Estruturas Metalorgânicas/síntese química , Estruturas Metalorgânicas/química , Metaloporfirinas/síntese química , Metaloporfirinas/química , Tamanho da Partícula , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Espécies Reativas de Oxigênio/metabolismo , Propriedades de Superfície
4.
ACS Appl Mater Interfaces ; 11(46): 42988-42997, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31650832

RESUMO

Until now, ferroptotic therapeutic strategies remain simple, although ferroptosis has aroused extensive interest owing to its escape from the biocarriers of conventional therapeutic modalities. Herein, we construct a photothermal (PT)- and autophagy-enhanced ferroptotic therapeutic modality based on MnO2@HMCu2-xS nanocomposites (HMCMs) for efficient tumor ablation. The HMCMs possess PT-enhanced glutathione (GSH) depletion capability, thereby inducing PT-enhanced ferroptosis via the reinforced inactivation of glutathione peroxidase 4 (GPX4). Thereafter, the GSH-responsed Mn2+ release could generate reactive oxygen species (ROS) by a Fenton-like reaction to reinforce the intracellular oxidative stress for the lipid hydroperoxide (LPO) accumulation in ferroptosis. Additionally, an autophagy promotor rapamycin (Rapa) was loaded into HMCM for sensitizing cells to ferroptosis due to the indispensable role of autophagy in the ferroptosis process. The in vitro and in vivo data demonstrated that the HMCM exhibited superior anticancer effect in human breast cancer models and that the combined therapeutic system afforded the next generation of ferroptotic therapy for combatting malignant tumors.


Assuntos
Autofagia/efeitos dos fármacos , Neoplasias da Mama , Ferroptose/efeitos dos fármacos , Glutationa Peroxidase/metabolismo , Hipertermia Induzida , Nanocompostos , Proteínas de Neoplasias/metabolismo , Fototerapia , Animais , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Feminino , Glutationa/metabolismo , Humanos , Células MCF-7 , Camundongos , Nanocompostos/química , Nanocompostos/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Colloids Surf B Biointerfaces ; 176: 230-238, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30623810

RESUMO

Tumor cells experience higher chemotherapy stress under condition of elevated temperature. As a result, developing novel nanoagents that integrates chemotherapy and thermotherapy holds great promise in biomedicine. Herein, utilizing spatially confined galvanic replacement method, we fabricated a yolk-shell Au@mSiO2 nanoframes with Au NPs and mesoporous silica as yolk and shell, respectively, to sever as an excellent drug nanocarrier with effective photothermal conversion efficiency. Taking full advantage of the high temperature response of the Au@mSiO2 nanoframes, the phase change material 1-tetradecanol (TD) was creatively employed as gatekeepers, intelligently controlling the release of loaded agents. Then, the actively targeted Alanine-Alanine-Asparagine, legumain-recognizable oligopeptides was decorated on the surface of the prepared nanoframes. Upon exposure to near-infrared light, the GC-PtAu@mSiO2-TD nanoframes not only exhibited a high localized temperature response, but also triggered the quick release of loaded cargos, and thus improved the chemotherapeutic efficacy. The in vitro cytotoxicity studies indicated the remarkable synergistic effects. Meanwhile, the laser confocal studies and flow cytometry showed the oligopeptides facilitated the intracellular uptake of GC-PtAu@mSiO2-TD nanoframes in MGC-803 cells. Our study highlighted the great potential of the GC-PtAu@mSiO2-TD nanoframes in drug delivery and the combination of chemotherapy and photothermal therapy.


Assuntos
Materiais Revestidos Biocompatíveis/química , Sistemas de Liberação de Medicamentos , Ouro/química , Hipertermia Induzida , Nanopartículas/química , Fototerapia , Dióxido de Silício/química , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cisplatino/farmacologia , Terapia Combinada , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Humanos , Nanopartículas/ultraestrutura , Nanosferas/química , Porosidade
6.
ACS Appl Mater Interfaces ; 10(37): 30930-30935, 2018 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-30183247

RESUMO

Herein, a biocompatible 2D metal-organic frameworks (Cu-TCPP(Fe)) based on TCPP(M) (TCPP = tetrakis (4-carboxyphenyl) porphyrin, M = Fe) and copper ion were synthesized as a novel drug carrier. Sequentially, the cisplatin was loaded on the merge of carboxyl-rich Cu-TCPP(Fe) through forming favorable carboxyl-drug interactions. The prepared Pt/Cu-TCPP(Fe) showed highly enhanced cytotoxicity than that of free cisplatin in human pulmonary carcinoma A549 cells, whereas inverse inhibitory effects were observed in human normal BEAS-2B cells. Further, the mechanism of action about the desirable results was also elaborated. Our study highlighted the potential synergies between the nanocarrier and the anticancer drugs.

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