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Int J Nanomedicine ; 19: 5193-5211, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38859958

RESUMO

Purpose: Ovarian cancer is a fatal gynecologic malignancy with a high rate of abdominal metastasis. Chemotherapy still has a poor clinical prognosis for ovarian cancer patients, with cell proliferation and angiogenesis leading to invasion, migration, and recurrence. To overcome these obstacles, we constructed a novel HA-modified paclitaxel and diosgenin liposome (PEG-TK-HA-PDLPs) using two novel functional materials, DSPE-PEG2000-HA and DSPE-PEG2000-TK-PEG5000, to specifically deliver the drugs to the tumor site in order to reduce OC cell proliferation and anti-angiogenic generation, thereby inhibiting invasion and migration. Methods and Results: PEG-TK-HA-PDLPs were prepared by film dispersion, with ideal physicochemical properties and exhibits active targeting for enhanced cellular uptake. The ZIP synergy score for PTX and Dios was calculated using the online SynergyFinder software to be 3.15, indicating synergy. In vitro results showed that PEG-TK-HA-PDLPs were highly cytotoxic to ID8 cells, induced ID8 cell apoptosis, and inhibited ID8 cell migration and invasion. In vivo studies showed that PEG-TK-HA-PDLPs could prolong the circulation time in the blood, accumulate significantly in the tumor site, and effectively fight against angiogenesis with significant anti-tumor effects. Conclusion: The production of PEG-TK-HA-PDLPs is an effective strategy for the treatment of OC.


Assuntos
Apoptose , Diosgenina , Ácido Hialurônico , Lipossomos , Neoplasias Ovarianas , Paclitaxel , Polietilenoglicóis , Espécies Reativas de Oxigênio , Feminino , Lipossomos/química , Lipossomos/farmacocinética , Paclitaxel/farmacologia , Paclitaxel/química , Paclitaxel/farmacocinética , Paclitaxel/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Diosgenina/farmacologia , Diosgenina/química , Diosgenina/farmacocinética , Diosgenina/administração & dosagem , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Linhagem Celular Tumoral , Polietilenoglicóis/química , Animais , Espécies Reativas de Oxigênio/metabolismo , Humanos , Apoptose/efeitos dos fármacos , Sinergismo Farmacológico , Proliferação de Células/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fosfatidiletanolaminas
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