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

Autor:	Hang Chen, Heyi Wang, Jianming Chen, Haiyan Zhang, Zhang Yuansheng, Xinmei Chen, Gu Yongwei, Sifan Huang, Xin Wu, Youfa Xu
Rok vydání:	2020
Předmět:	media_common.quotation_subject Pharmaceutical Science RM1-950 02 engineering and technology anti-tumor effect Endocytosis 030226 pharmacology & pharmacy 03 medical and health sciences Prostate cancer 0302 clinical medicine In vivo bone-metastases prostate cancer LNCaP medicine administration safety Internalization media_common cellular internalization mechanisms Chemistry Bone metastasis Cell migration General Medicine 021001 nanoscience & nanotechnology medicine.disease gene therapy Blood chemistry Cancer research Therapeutics. Pharmacology 0210 nano-technology
Zdroj:	Drug Delivery, Vol 27, Iss 1, Pp 161-169 (2020)
ISSN:	1521-0464 1071-7544
DOI:	10.1080/10717544.2019.1709923
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8ac81ce3f85350559a2b388ead87ee8c https://doi.org/10.1080/10717544.2019.1709923 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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