Feng Liandong, Wang Yuqi, Luo Zhiliang, Huang Zheng, Zhang Yan, Guo Kai, Ye Deju
State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, P.R. China.
State Key Laboratory of Materials-Oriented Chemical Engineering, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, 210023, P.R. China.
Chemistry. 2017 Jul 12;23(39):9397-9406. doi: 10.1002/chem.201701524. Epub 2017 Jun 19.
Dual stimuli-responsive nanoparticles capable of fine-tuning drug release to augment therapeutic efficacy have become a promising tool for anticancer drug delivery. However, the rational design of these "smart" nanoparticles for a selective delivery and controlled release of multidrug combinations in cancer cells to achieve synergistic effects remain challenging. Here we report the pH/redox dual responsive nanoparticle FA-DOX-Ind-NP (FA=folic acid, DOX=doxorubicin, Ind=indomethacin, NP=nanoparticle) based on the novel tumor targeting and biodegradable poly(β-amino ester) polymer, and demonstrate its high ability to enter into cancer cells and release a combination of the anticancer drug doxorubicin and the non-steroidal anti-inflammatory drug indomethacin to achieve synergistic chemo-anti-inflammatory effects and overcome multidrug resistance. This study highlights the great potential of tumor targeting and dual stimuli-responsive nanoparticles for an efficient delivery of multidrug combination to improve the cancer therapeutic efficacy.
能够微调药物释放以增强治疗效果的双刺激响应性纳米颗粒已成为抗癌药物递送的一种有前途的工具。然而，合理设计这些“智能”纳米颗粒以在癌细胞中选择性递送和控制释放多药组合以实现协同效应仍然具有挑战性。在此，我们报道了基于新型肿瘤靶向和可生物降解的聚（β-氨基酯）聚合物的pH/氧化还原双响应性纳米颗粒FA-DOX-Ind-NP（FA=叶酸，DOX=阿霉素，Ind=吲哚美辛，NP=纳米颗粒），并证明其具有高能力进入癌细胞并释放抗癌药物阿霉素和非甾体抗炎药吲哚美辛的组合，以实现协同化学抗炎作用并克服多药耐药性。这项研究突出了肿瘤靶向和双刺激响应性纳米颗粒在高效递送多药组合以提高癌症治疗效果方面的巨大潜力。
