GANT61 and curcumin-loaded PLGA nanoparticles for GLI1 and PI3K/Akt-mediated inhibition in breast adenocarcinoma
GANT61 and curcumin-loaded PLGA nanoparticles for GLI1 and PI3K/Akt-mediated inhibition in breast adenocarcinoma
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DOI：
10.1088/1361-6528/ab6d20
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发表时间：
2020-05-01
期刊：
影响因子：
3.5
通讯作者：
Kumar, D. Sakthi
中科院分区：
文献类型：
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作者：
Borah, Ankita;Pillai, Sindhu C.;Kumar, D. Sakthi
目前传统的单一和联合治疗策略往往不能有效地靶向乳腺癌组织，因为肿瘤包括癌症干细胞（CSCs）和大块肿瘤细胞的异质性。从长远来看，这与药物毒性和电阻率进一步相关。结合联合抗癌治疗的纳米药物平台可能会克服这些挑战，产生协同抗癌效果，并降低药物毒性。GANT61和姜黄素首次通过聚合物纳米颗粒（NPs）共递送，增强了对异质性乳腺癌细胞系MCF-7的抗肿瘤活性。我们采用单乳液-溶剂蒸发法制备治疗性NPs。gant61 -姜黄素PLGA NPs以其大小、形状和化学性质进行了表征，并进行了抗癌细胞研究，以合理解释我们的假设。合成的gant61 -姜黄素PLGA NPs具有球形、光滑的表面形态，平均大小为347.4 d. nm。体外细胞研究表明，NPs在中最小剂量下诱导乳腺癌细胞产生细胞毒作用，随后细胞通过自噬和凋亡死亡，其靶蛋白表达降低，并损害CSCs的自我更新特性。因此，双药NPs为帮助现有的抗癌纳米药物治疗有效靶向异质性肿瘤肿块提供了一个新的视角。
Current conventional mono and combination therapeutic strategies often fail to target breast cancer tissue effectively due to tumor heterogeneity comprising cancer stem cells (CSCs) and bulk tumor cells. This is further associated with drug toxicity and resistivity in the long run. A nanomedicine platform incorporating combination anti-cancer treatment might overcome these challenges and generate synergistic anti-cancer effects and also reduce drug toxicity. GANT61 and curcumin were co-delivered via polymeric nanoparticles (NPs) for the first time to elicit enhanced anti-tumor activity against heterogeneous breast cancer cell line MCF-7. We adopted the single-emulsion-solvent evaporation method for the preparation of the therapeutic NPs. The GANT61-curcumin PLGA NPs were characterized for their size, shape and chemical properties, and anti-cancer cell studies were undertaken for the plausible explanation of our hypothesis. The synthesized GANT61-curcumin PLGA NPs had a spherical, smooth surface morphology, and an average size of 347.4 d. nm. The NPs induced cytotoxic effects in breast cancer cells at a midminimal dosage followed by cell death via autophagy and apoptosis, reduction in their target protein expression along with compromising the self-renewal property of CSCs as revealed by their in vitro cell studies. The dual-drug NPs thus provide a novel perspective on aiding existing anti-cancer nanomedicine therapies to target a heterogeneous tumor mass effectively.