Study on the prostate cancer-targeting mechanism of aptamer-modified nanoparticles and their potential anticancer effect in vivo

Abstract

Xin Wu,1,2,* Zongguang Tai,1,* Quangang Zhu,3,* Wei Fan,4 Baoyue Ding,5 Wei Zhang,1,6 Lijuan Zhang,1 Chong Yao,1 Xiaoyu Wang,1 Xueying Ding,2 Qin Li,2 Xiaoyu Li,2 Gaolin Liu,2 Jiyong Liu,1 Shen Gao1 1Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, 2Department of Pharmaceutics, Shanghai First People’s Hospital, Shanghai Jiaotong University School of Medicine, 3Department of Pharmaceutics, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Department of Pharmaceutics, The 425th Hospital of PLA, Sanya, People’s Republic of China; 5Department of Pharmaceutics, Medical College of Jiaxing University, Jiaxing, People’s Republic of China; 6Department of Pharmaceutics, The 522nd Hospital of PLA, Luoyang, People’s Republic of China *These authors contributed equally to this work Abstract: Ligand-mediated prostate cancer (PCa)-targeting gene delivery is one of the focuses of research in recent years. Our previous study reported the successful preparation of aptamer-modified nanoparticles (APT-NPs) in our laboratory and demonstrated their PCa-targeting ability in vitro. However, the mechanism underlying this PCa-targeting effect and their anticancer ability in vivo have not yet been elucidated. The objective of this study was to assess the feasibility of using APT-NPs to deliver micro RNA (miRNA) systemically to PCa cells, to testify their tumor-targeting efficiency, and to observe their biodistribution after systemic administration to a xenograft mouse model of PCa. In addition, the effect of APT depletion and endocytosis inhibitors on cellular uptake was also evaluated quantitatively in LNCaP cells to explore the internalization mechanism of APT-NPs. Finally, blood chemistry, and renal and liver function parameters were measured in the xenograft mouse model of PCa to see whether APT-NPs had any demonstrable toxicity in mice in vivo. The results showed that APT-NPs prolonged the survival duration of the PCa tumor-bearing mice as compared with the unmodified NPs. In addition, they had a potential PCa-targeting effect in vivo. In conclusion, this research provides a prototype for the safe and efficient delivery of miRNA expression vectors to PCa cells, which may prove useful for preclinical and clinical studies on the treatment of PCa. Keywords: miRNA, aptamer, polyamidoamine, prostate-specific membrane antigen, targeted delivery, prostate cancer