International Journal of Nanomedicine (Jun 2019)

Hyaluronic acid-decorated redox-sensitive chitosan micelles for tumor-specific intracellular delivery of gambogic acid

  • Xu W,
  • Wang H,
  • Dong L,
  • Zhang P,
  • Mu Y,
  • Cui X,
  • Zhou J,
  • Huo M,
  • Yin T

Journal volume & issue
Vol. Volume 14
pp. 4649 – 4666

Abstract

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Wei Xu,1,2 Honglan Wang,3 Lihui Dong,3 Pan Zhang,3 Yan Mu,2 Xueyan Cui,2 Jianping Zhou,3 Meirong Huo,3 Tingjie Yin31Department of Pharmacy, Shandong Provincial Qian Foshan Hospital, Shandong University, Jinan 250014, People’s Republic of China; 2Qianfoshan Hospital, The First Hospital Affiliation with Shandong First Medical University, Jinan 250012, People’s Republic of China; 3State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, People’s Republic of ChinaIntroduction: Herein, a hyaluronic acid (HA)-coated redox-sensitive chitosan-based nanoparticle, HA(HECS-ss-OA)/GA, was successfully developed for tumor-specific intracellular rapid delivery of gambogic acid (GA).Materials and methods: The redox-sensitive polymer, HECS-ss-OA, was prepared through a well-controlled synthesis procedure with a satisfactory reproducibility and stable resulted surface properties of the assembled cationic micelles. GA was solubilized into the inner core of HECS-ss-OA micelles, while HA was employed to coat outside HECS-ss-OA/GA for CD44-mediated active targeting along with protection from cation-associated in vivo defects. The desirable redox-sensitivity of HA(HECS-ss-OA)/GA was demonstrated by morphology and particle size changes alongside in vitro drug release of nanoparticles in different simulated reducing environments.Results: The results of flow cytometry and confocal microscopy confirmed the HA-receptor mediated cellular uptake and burst drug release in highly reducing cytosol of HA(HECS-ss-OA)/GA. Consequently, HA(HECS-ss-OA)/GA showed the highest apoptosis induction and cytotoxicity over the non-sensitive (HA(HECS-cc-OA)/GA) and HA un-coated (HECS-ss-OA/GA) controls against A549 NSCLC model both in vitro and in vivo. Furthermore, a diminished systemic cytotoxicity was observed in HA(HECS-ss-OA)/GA treated mice compared with those treated by HA un-coated cationic ones and GA solution.Keywords: gambogic acid, nanoparticles, redox-sensitive, intracellular drug delivery, tumor

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