National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu, Sichuan 610064, PR China; Center for Molecular Science and Engineering, College of Science, Northeastern University, Shenyang 110819, PR China.
National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu, Sichuan 610064, PR China.
J Control Release. 2020 Oct 10;326:350-364. doi: 10.1016/j.jconrel.2020.07.030. Epub 2020 Jul 21.
Stimuli-responsive nanotechnology-mediated drug co-delivery system is a notable strategy to improve access of the systemically administered chemotherapeutics to the tumors. Herein, a tailor-made 2,3-dimethylmaleic-anhydride-poly(ethylene glycol)-ε-poly-l-lysine-doxorubicin /lapatinib polymeric nanoplatform (DMMA-P-DOX/LAP) for synergistically eliminating breast cancer is developed by encapsulating lapatinib into dual-pH responsive charge switchable biopolymer-doxorubicin conjugate nanoparticles. The physicochemical properties of polymeric nanoparticles are conducive to their stable circulation in the physiological condition, but reverse the surface charge from negative to positive ultrasensitively in slightly acidic tumor microenvironment, facilitating cell internalization and deep tumor penetration. Subsequently, DOX and LAP are synchronously released into the cytoplasm in response to the significantly increased acidity of intracellular environment. As a result, the combination therapy by DMMA-P-DOX/LAP nanoparticles compels the solid tumors to contract significantly or even vanish completely in the MCF-7 tumor model, moreover, the structural composition with amino acid and bioinert PEG ensures the favorable biosecurity of the co-delivery system in vivo. This dual-pH responsive nanotechnology-mediated drug co-delivery system provides great potentials for safe and effective cancer therapy.
刺激响应型纳米技术介导的药物共递药系统是提高系统给药化疗药物进入肿瘤的一种显著策略。在此，通过将拉帕替尼包封入双 pH 响应电荷可切换的生物聚合物-阿霉素偶联物纳米颗粒中，开发了一种用于协同消除乳腺癌的定制 2,3-二甲基马来酸酐-聚乙二醇-ε-聚-l-赖氨酸-阿霉素/拉帕替尼聚合物纳米平台（DMMA-P-DOX/LAP）。聚合物纳米颗粒的理化性质有利于其在生理条件下稳定循环，但在轻微酸性肿瘤微环境中，表面电荷从负到正超灵敏反转，有利于细胞内化和深层肿瘤渗透。随后，DOX 和 LAP 响应细胞内环境酸度的显著增加而同步释放到细胞质中。结果，DMMA-P-DOX/LAP 纳米颗粒的联合治疗迫使 MCF-7 肿瘤模型中的实体瘤显著收缩，甚至完全消失，此外，具有氨基酸和生物惰性 PEG 的结构组成确保了共递药系统在体内的良好生物安全性。这种双 pH 响应型纳米技术介导的药物共递药系统为安全有效的癌症治疗提供了巨大的潜力。
