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Polyphosphazene-Based Drug Self-Framed Delivery System as a Universal Intelligent Platform for Combination Therapy against Multidrug-Resistant Tumors
ACS Applied Bio Materials ( IF 4.6 ) Pub Date : 2020-03-09 , DOI: 10.1021/acsabm.0c00072
Shenglei Hou 1 , Shiliu Zhou 1 , Shuangshuang Chen 2 , Qinghua Lu 1
Affiliation  

Combination therapy is a burgeoning research field due to the advantages of the synergistic contributions from incorporating drugs and promising potentials in the therapy of aggressive tumors with multidrug resistance (MDR). Given the great efforts, it is extremely difficult to coordinate pharmacokinetics between drugs and elucidate the mechanism of synergistic effects. Additionally, limited by the inherent solubility of anticancer drugs, a common strategy for simultaneously delivering various drugs is yet a challenging target. To overcome these, we develop a drug self-framed delivery system (DSFDS) via treating multiple drugs as monomers to constructing cyclomatrix polyphosphazene nanoparticles (CPPZ NPs). Notably, it is a superflexible common platform to realize the rational design of combination therapy, which is verified by delivering doxorubicin (DOX) with mitoxantrone (Mit), resveratrol (RES), curcumin (Cur), and porphyrin (TPP). As a proof of concept, DOX-RES-CysM-CPPZ NP was selected to evaluate the therapeutic feasibility of DSFDSs. Obvious improvement in killing MDR tumors indicated an efficient combination therapy. The corresponding synergistic mechanism of DOX and RES was also addressed in this work. Throughout cutting-edge research, the drug self-framed delivery system is drawing promising blueprint for combination therapy.

中文翻译:

基于聚磷腈的药物自框架递送系统作为多药耐药肿瘤联合治疗的通用智能平台

联合治疗是一个新兴的研究领域,因为结合药物具有协同作用的优势,以及在治疗具有多药耐药性(MDR)的侵袭性肿瘤方面的潜力。由于付出了巨大的努力,很难协调药物之间的药代动力学并阐明协同作用的机制。此外,受抗癌药物固有溶解度的限制,同时递送多种药物的通用策略仍然是一个具有挑战性的目标。为了克服这些问题,我们开发了一种药物自框架递送系统(DSFDS),通过将多种药物作为单体来构建环基质聚磷腈纳米颗粒(CPPZ NPs)。值得一提的是,它是实现联合疗法合理设计的超灵活通用平台,这是通过提供多柔比星 (DOX) 与米托蒽醌 (Mit)、白藜芦醇 (RES)、姜黄素 (Cur) 和卟啉 (TPP) 来验证的。作为概念验证,选择 DOX-RES-CysM-CPPZ NP 来评估 DSFDS 的治疗可行性。杀死 MDR 肿瘤的明显改善表明有效的联合治疗。DOX 和 RES 的相应协同机制也在这项工作中得到解决。纵观前沿研究,药物自框架递送系统正在为联合治疗绘制有希望的蓝图。DOX 和 RES 的相应协同机制也在这项工作中得到解决。纵观前沿研究,药物自框架递送系统正在为联合治疗绘制有希望的蓝图。DOX 和 RES 的相应协同机制也在这项工作中得到解决。纵观前沿研究,药物自框架递送系统正在为联合治疗绘制有希望的蓝图。
更新日期:2020-04-23
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