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1.
Int J Nanomedicine ; 18: 1299-1315, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36945255

RESUMO

Background: Chemotherapy still plays a dominant role in cancer treatment. However, the inability of conventional chemotherapeutic drugs to reach the hypoxic zone of solid tumors significantly weakens their efficacy. Bacteria-mediated drug delivery systems can be an effective targeting strategy for improving the therapeutic outcomes in cancer. Anaerobic bacteria have the unique ability to selectively transport drug loads to the hypoxic regions of tumors. Methods: We designed a Bifidobacterium infantis (Bif)-based biohybrid (Bif@PDA-PTX-NPs) to deliver polydopamine (PDA)-coated paclitaxel nanoparticles (PTX-NPs) to tumor tissues. Results: The self-driven Bif@PDA-PTX-NPs maintained the toxicity of PTX as well as the hypoxic homing tendency of Bif. Furthermore, Bif@PDA-PTX-NPs significantly inhibited the growth of A549 xenografts in nude mice, and prolonged the survival of the tumor-bearing mice compared to the other PTX formulations without any systemic or localized toxicity. Conclusion: The Bif@PDA-PTX-NPs biohybrids provide a new therapeutic strategy for targeted chemotherapy to solid tumors.


Assuntos
Neoplasias Pulmonares , Nanopartículas , Humanos , Animais , Camundongos , Camundongos Nus , Microambiente Tumoral , Linhagem Celular Tumoral , Paclitaxel/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Sistemas de Liberação de Medicamentos , Bactérias , Camundongos Endogâmicos BALB C
2.
Drug Deliv ; 29(1): 2713-2722, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35975331

RESUMO

Malignant ascites is a common complication of some advanced cancers. Although intraperitoneal (IP) administration of chemotherapy drugs is routinely used to treat cancerous ascites, conventional drugs have poor retention and therefore need to be administered frequently to maintain a sustained anti-tumor effect. In this study, a thermosensitive hydrogel composite loaded with norethindrone nanoparticles (NPs) and oxaliplatin (N/O/Hydrogel) was developed to inhibit ascites of hepatocellular carcinoma (HCC) through IP injection. N/O/Hydrogel induced apoptosis in the H22 cells in vitro, and significantly inhibited ascites formation, tumor cell proliferation and micro-angiogenesis in a mouse model of advanced HCC with ascites, and prolonged the survival of tumor-bearing mice. Histological examination of the major organs indicated that the hydrogel system is safe. Taken together, the N/O/Hydrogel system is a promising platform for in-situ chemotherapy of malignant ascites.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanopartículas , Neoplasias Peritoneais , Animais , Ascite/tratamento farmacológico , Ascite/patologia , Compostos Bicíclicos Heterocíclicos com Pontes , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Hidrogéis , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Camundongos , Oxaliplatina , Neoplasias Peritoneais/tratamento farmacológico
3.
J Nanobiotechnology ; 20(1): 178, 2022 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-35366890

RESUMO

Local hypoxia is a common feature of many solid tumors and may lead to unsatisfactory chemotherapy outcomes. Anaerobic bacteria that have an affinity to hypoxic areas can be used to achieve targeted drug delivery in tumor tissues. In this study, we developed a biocompatible bacteria/nanoparticles biohybrid (Bif@DOX-NPs) platform that employs the anaerobic Bifidobacterium infantis (Bif) to deliver adriamycin-loaded bovine serum albumin nanoparticles (DOX-NPs) into breast tumors. The Bif@DOX-NPs retained the targeting ability of B. infantis to hypoxic regions, as well as the cytotoxicity of DOX. The biohybrids were able to actively colonize the hypoxic tumors and significantly increased drug accumulation at the tumor site. The DOX concentration in the tumor masses colonized by Bif@DOX-NPs was 4 times higher than that in the free DOX-treated tumors, which significantly prolonged the median survival of the tumor-bearing mice to 69 days and reduced the toxic side-effects of DOX. Thus, anaerobic bacteria-based biohybrids are a highly promising tool for the targeted treatment of solid tumors with inaccessible hypoxic regions.


Assuntos
Nanopartículas , Neoplasias , Animais , Bactérias , Doxorrubicina , Sistemas de Liberação de Medicamentos , Hipóxia/tratamento farmacológico , Camundongos , Neoplasias/tratamento farmacológico
4.
Int J Biol Macromol ; 193(Pt A): 228-237, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34688683

RESUMO

Conventional chemotherapeutic drugs may cause serious side effects such as hepatotoxicity and renal toxicity due to lack of targeting, which affects therapy outcome and the prognosis of patients. Therefore, biomimetic nanoparticles with long blood circulation and active targeting have attracted increasing attention. In this work, we fabricated a biomimetic R-RBC@GEF-NPs nano-system by encapsulating gefitinib-loaded albumin nanoparticles (GEF-NPs) inside cRGD-modified red blood cell (RBC) membranes. The complete RBC membrane structure and membrane proteins enabled the NPs to escape phagocytosis by macrophages. In addition, the cRGD moiety significantly improved tumor cell targeting and uptake. R-RBC@GEF-NPs inhibited the growth of A549 cells in vitro in a dose- and time-dependent manner by inducing apoptosis and cell cycle arrest at the G1 phase. Likewise, the R-RBC@GEF-NPs also decreased tumor weight and volume in the mice injected with A549 cells and prolonged survival time. In addition, the 99Tc-labeled R-RBC@GEF-NPs selectively accumulated in the tumor tissues in vivo, and enabled real time tumor imaging. Finally, blood and histological analyses showed that R-RBC@GEF-NPs did not cause any obvious systemic toxicity. Taken together, the biomimetic R-RBC@GEF-NPs is a promising therapeutic formulation for the treatment of lung cancer.


Assuntos
Albuminas/química , Portadores de Fármacos , Gefitinibe/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Nanopartículas/administração & dosagem , Células A549 , Animais , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Humanos , Camundongos , Camundongos Nus
5.
Regen Biomater ; 8(2): rbab009, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33738123

RESUMO

Dermal injury, including trauma, surgical incisions, and burns, remain the most prevalent socio-economical health care issue in the clinic. Nanomedicine represents a reliable administration strategy that can promote the healing of skin lesions, but the lack of effective drug delivery methods can limit its effectiveness. In this study, we developed a novel nano-drug delivery system to treat skin defects through spraying. We prepared curcumin-loaded chitosan nanoparticles modified with epidermal growth factor (EGF) to develop an aqueous EGF-modified spray (EGF@CCN) for the treatment of dermal wounds. In vitro assays showed that the EGF@CCN displayed low cytotoxicity, and that curcumin was continuously and slowly released from the EGF@CCN. In vivo efficacy on wound healing was then evaluated using full-thickness dermal defect models in Wistar rats, showing that the EGF@CCN had significant advantages in promoting wound healing. On day 12 post-operation, skin defects in the rats of the EGF@CCN group were almost completely restored. These effects were related to the activity of curcumin and EGF on skin healing, and the high compatibility of the nano formulation. We therefore conclude that the prepared nano-scaled EGF@CCN spray represents a promising strategy for the treatment of dermal wounds.

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