Nanomedicine solutions to intricate physiological-pathological barriers and molecular mechanisms of tumor multidrug resistance.,Journal of Controlled Release

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Nanomedicine solutions to intricate physiological-pathological barriers and molecular mechanisms of tumor multidrug resistance.
Journal of Controlled Release ( IF 10.5 ) Pub Date : 2020-05-05 , DOI: 10.1016/j.jconrel.2020.05.007
Yachao Li ₁ , Xianghui Xu ₁

Affiliation

Cancer multidrug resistance (MDR) has been a fatal factor for the failure of clinical chemotherapy, accompanying with tumor metastasis and recurrence. The mechanisms of MDR are extremely complicated, diversifying from tumor physiological-pathological barriers to molecular mechanisms of cellular factors. Especially, certain hard biological barriers (such as tumor tissue barriers and tumor subcellular compartments) are found to have close relationship with multidrug resistance, and increasing attentions are paid to address the MDR-related physiopathologic barriers for optimal drug distribution and bioavailability. Molecular and genetic factors of multidrug resistance are also gradually disclosed, such as decreased drug influx, increased drug efflux, altered drug targets, aberrant apoptotic pathway and activated DNA repair. To cope with these challenges, diverse nanomedicine solutions have been developed for overcoming physiological-pathological barriers and molecular mechanisms in the treatment of drug-resistant tumors. This review first introduces that multifunctional nanomedicines break through sequential physiological-pathological barriers to reverse MDR, including prolonged in vivo blood circulation, improved drug tumor penetration and intratumoral distribution, increased cellular internalization, optimized subcellular targeting and sufficient drug release. For another, nanomedicine solutions also show immense potentials on provoking multiple mechanisms for MDR reversal, such as decreasing drug efflux, strengthening tumor apoptosis and suppressing anti-apoptosis.

中文翻译：

复杂的生理病理屏障和肿瘤多药耐药性分子机制的纳米医学解决方案。

癌症多药耐药性（MDR）已成为导致临床化疗失败以及肿瘤转移和复发的致命因素。MDR的机制极为复杂，从肿瘤的生理病理障碍到细胞因子的分子机制，多种多样。尤其是，发现某些坚硬的生物屏障（例如肿瘤组织屏障和肿瘤亚细胞区室）与多药耐药性有着密切的关系，因此人们越来越重视解决与MDR相关的生理病理屏障，以实现最佳的药物分布和生物利用度。还逐渐揭示了多药耐药性的分子和遗传因素，例如减少的药物流入，增加的药物流出，改变的药物靶标，异常的凋亡途径和活化的DNA修复。为了应对这些挑战，已经开发出多种纳米药物解决方案来克服耐药性肿瘤治疗中的生理病理障碍和分子机制。这篇综述首先介绍了多功能纳米药物突破了连续的生理病理学障碍以逆转MDR，包括延长体内血液循环，改善了药物肿瘤的渗透和肿瘤内分布，增加了细胞内在化，优化了亚细胞靶向和充分的药物释放。另外，纳米药物溶液还具有激发多重逆转MDR的巨大潜力，例如降低药物外流，增强肿瘤细胞凋亡和抑制抗凋亡。已经开发出多种纳米药物解决方案来克服耐药性肿瘤治疗中的生理病理障碍和分子机制。这篇综述首先介绍了多功能纳米药物突破了连续的生理病理学障碍以逆转MDR，包括延长体内血液循环，改善了药物肿瘤的渗透和肿瘤内分布，增加了细胞内在化，优化了亚细胞靶向和充分的药物释放。另外，纳米药物溶液还具有激发多重逆转MDR的巨大潜力，例如降低药物外流，增强肿瘤细胞凋亡和抑制抗凋亡。已经开发出多种纳米药物溶液来克服耐药性肿瘤治疗中的生理病理障碍和分子机制。这篇综述首先介绍了多功能纳米药物突破了连续的生理病理学障碍以逆转MDR，包括延长体内血液循环，改善了药物肿瘤的渗透和肿瘤内分布，增加了细胞内在化，优化了亚细胞靶向和充分的药物释放。另外，纳米药物溶液还具有激发多重逆转MDR的巨大潜力，例如降低药物外流，增强肿瘤细胞凋亡和抑制抗凋亡。这篇综述首先介绍了多功能纳米药物突破了连续的生理病理学障碍以逆转MDR，包括延长体内血液循环，改善了药物肿瘤的渗透和肿瘤内分布，增加了细胞内在化，优化了亚细胞靶向和充分的药物释放。另外，纳米药物溶液还具有激发多重逆转MDR的巨大潜力，例如降低药物外流，增强肿瘤细胞凋亡和抑制抗凋亡。这篇综述首先介绍了多功能纳米药物突破了连续的生理病理学障碍以逆转MDR，包括延长体内血液循环，改善了药物肿瘤的渗透和肿瘤内分布，增加了细胞内在化，优化了亚细胞靶向和充分的药物释放。另外，纳米药物溶液还具有激发多重逆转MDR的巨大潜力，例如降低药物外流，增强肿瘤细胞凋亡和抑制抗凋亡。

更新日期：2020-05-05

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