Journal of Southern Medical University

Journal of Southern Medical University ›› 2022, Vol. 42 ›› Issue (1): 26-35.doi: 10.12122/j.issn.1673-4254.2022.01.03

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Targeted killing of CD133+ lung cancer stem cells using paclitaxel-loaded PLGA-PEG nanoparticles with CD133 aptamers

PANG Liying, HUANG Xiaolong, ZHU Lingling, XIAO Hanyan, LI Mengyu, GUAN Huilin, GAO Jie, JIN Hong   

  1. First School of Clinical Medicine, Mudanjiang Medical University; Clinical Laboratory, Department of Hematology, Affiliated Hongqi Hospital, Mudanjiang Medical University; Department of Respiratory and Critical Care Medicine, Wuhan First Hospital; Institute of Translational Medicine, Shanghai University; Department of Obstetrics and Gynecology, Second Affiliated Hospital of Mudanjiang Medical University; Research Department, Mudanjiang Medical University
  • Online:2022-01-20 Published:2022-03-02

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Abstract: Objective To construct a polylactic acid-glycolic acid-polyethylene glycol (PLGA-PEG) nanocarrier (N-Pac-CD133) coupled with a CD133 nucleic acid aptamer carrying paclitaxel for eliminating lung cancer stem cells (CSCs). Methods Paclitaxel-loaded N-Pac-CD133 was prepared using the emulsion/solvent evaporation method and characterized. CD133+ lung CSCs were separated by magnetic bead separation and identified for their biological behaviors and gene expression profile. The efficiency of paclitaxel-loaded N-Pac-CD133 for targeted killing of lung cancer cells was assessed in vitro. SCID mice were inoculated with A549 cells and received injections of normal saline, empty nanocarrier linked with CD133 aptamer (N-CD133),paclitaxel, paclitaxel-loaded nanocarrier (N-Pac) or paclitaxel-loaded N-Pac-CD133 (n=8, 5 mg/kg paclitaxel) on days 10, 15 and 20, and the tumor weight and body weight of the mice were measured on day 40. Results Paclitaxel-loaded N-Pac-CD133 showed a particle size of about 100 nm with a high encapsulation efficiency (>80%) and drug loading rate (>8%), and was capable of sustained drug release within 48 h. The CD133+ cell population in lung cancer cells showed the characteristic features of lung CSCs, including faster growth rate (30 days,P=0.001) and high expressions of tumor stem cell markers OV6(P< 0.001), CD133 (P=0.001), OCT3/4 (P=0.002), EpCAM (P=0.04), NANOG (P=0.005) and CD44 (P=0.02). Compared with N-Pac and free paclitaxel, paclitaxel-loaded N-Pac-CD133 showed significantly enhanced targeting ability and cytotoxicity against lung CSCs in vitro (P<0.001) and significantly reduced the formation of tumor spheres (P<0.001). In the tumor-bearing mice, paclitaxel-loaded N-Pac-CD133showed the strongest effects in reducing the tumor mass among all the treatments (P<0.001). Conclusion CD133 aptamer can promote targeted delivery of paclitaxel to allow targeted killing of CD133+ lung CSCs. N-Pac-CD133 loaded with paclitaxel may provide an effective treatment for lung cancer by targeting the lung cancer stem cells.

Key words: nanoparticles; lung cancer; paclitaxel; cancer stem cells; CD133