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Lipid-polymer hybrid nanoparticle with cell-distinct drug release for treatment of stemness-derived resistant tumor

Acta Pharmaceutica Sinica B 2023年第3期13卷 1262-1273页

作者： Shiyang Shen Teng Li Jinyi Fan Quanlin Shao He Dong Xiao Xu Ran Mo State Key Laboratory of Natural Medicines Jiangsu Key Laboratory of Drug Discovery for Metabolic DiseasesCenter of Advanced Pharmaceuticals and BiomaterialsSchool of Life Science and TechnologyChina Pharmaceutical UniversityNanjing 210009China

Drug resistance presents one of the major causes for the failure of cancer chemotherapy.Cancer stem-like cells(CSCs),a population of self-renewal cells with high tumorigenicity and innate chemoresistance,can survive conventional chemotherapy and generate increased resistance.Here,we develop a lipid-polymer hybrid nanoparticle for co-delivery and cell-distinct release of the differentiation-inducing agent,all-trans retinoic acid and the chemotherapeutic drug,doxorubicin to overcome the CSC-associated chemoresistance.The hybrid nanoparticles achieve differential release of the combined drugs in the CSCs and bulk tumor cells by responding to their specific intracellular signal variation.In the hypoxic CSCs,ATRA is released to induce differentiation of the CSCs,and in the differentiating CSCs with decreased chemoresistance,DOX is released upon elevation of reactive oxygen species to cause subsequent cell death.In the bulk tumor cells,the drugs are released synchronously upon the hypoxic and oxidative conditions to exert potent anticancer effect.This cell-distinct drug release enhances the synergistic therapeutic efficacy of ATRA and DOX with different anticancer mechanism.We show that treatment with the hybrid nanoparticle efficiently inhibit the tumor growth and metastasis of the CSC-enriched triple negative breast cancer in the mouse models.

关键词： Drug delivery Lipid-polymer hybrid nanoparticle chemotherapeutic resistance Cancer stem-like cell Differentiation therapy

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Long non-coding RNAs regulation of therapeutic resistance

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Cancer Drug resistance 2019年第3期2卷 550-567页

作者： Susan Tsang Tajhal Patel Jason T.Yustein Integrative Molecular and Biomedical Sciences Program Baylor College of MedicineHoustonTX 77030USA Department of Pediatrics Texas Children’s Cancer CenterBaylor College of MedicineHoustonTX 77030USA.

Non-protein coding RNAs have emerged as a regulator of cell signaling and cancer progression through regulation of cell proliferation,metastatic burden,and cancer stem cell capacity.A subtype of non-protein coding RNA is long non-protein coding RNA(lncRNA).Besides their aforementioned roles in cancer cell biology,dysregulation of lncRNAs contribute to resistance to therapeutic treatments.A couple of important therapeutic classes are chemotherapy and targeted/hormone therapies.This review highlights the variety of malignancies affected by lncRNA dysregulation and the underlying mechanism causing therapeutic resistance.

关键词： Long non-protein coding RNA cancer chemotherapeutic resistance target therapeutics hormone therapy and microRNA sponge

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