Study on the cellular internalization mechanisms and in vivo anti-bone metastasis prostate cancer efficiency of the peptide T7-modified polypeptide nanoparticles

• Published in: Drug delivery 2020-01, Vol.27 (1), p.161-169
• Main Authors: Gu, Yongwei, Chen, Xinmei, Zhang, Haiyan, Wang, Heyi, Chen, Hang, Huang, Sifan, Xu, Youfa, Zhang, Yuansheng, Wu, Xin, Chen, Jianming
• Format: Article
• Language: English
• Subjects: administration safety; Animals; anti-tumor effect; Arginine; Aspartic Acid; Bone Neoplasms - prevention & control; Bone Neoplasms - secondary; bone-metastases prostate cancer; Cell adhesion & migration; Cell Line, Tumor; Cell Movement; Cell Survival; cellular internalization mechanisms; Cysteine; Gene therapy; Genetic Vectors - chemistry; Genetic Vectors - pharmacology; Male; Membrane Proteins - genetics; Metastasis; Mice; Mice, Inbred BALB C; Nanoparticles; Nanoparticles - chemistry; Particle Size; Peptide Fragments; Peptide T; Polyethylene Glycols - chemistry; Polypeptides; Prostate cancer; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Tumor Burden
• ISSN: 1071-7544; 1521-0464
• DOI: 10.1080/10717544.2019.1709923

Bone-metastasis prostate cancer (BMPCa)-targeting gene therapy is gaining increasing concern in recent years. The peptide T7-modified polypeptide nanoparticles for delivery DNA (CRD-PEG-T7/pPMEPA1) was prepared as our previous study. However, the feasibility of CRD-PEG-T7/pPMEPA1 for BMPCa treatment, the mechanisms underlying cellular uptake, anti-BMPCa effect, and administration safety requires further research. LNCaP cells treated with endocytosis inhibitors and excessive T7 under different culture condition were carried out to investigate the mechanisms of cellular uptake of the CRD-PEG-T7-pPMEPA1. A transwell assay was applied to evaluate the cell migration ability. Besides, the tumor volume and survival rates of the PCa xenograft mice model were recorded to estimate the anti-tumor effect. In addition, the weight profiles of the PCa tumor-bearing mice, the blood chemistry, and the HE analysis of visceral organs and tumor was conducted to investigate the administration safety of CRD-PEG-T7/pPMEPA1. The results showed that PCa cellular uptake was decreased after treating with excessive free T7, endocytosis inhibitors and lower incubation temperature. Besides, CRD-PEG-T7/pPMEPA1 could inhibit the LNCaP cells chemotaxis and tumor growth. In addition, the survival duration of the PCa tumor-bearing mice treating with CRD-PEG-T7/pPMEPA1 was significantly prolonged with any systemic toxicity or damage to the organs. In conclusion, this research proposes a promising stratagem for treatment BMPCa by providing the biocompatible and effective carrier for delivery DNA therapeutic agents.