PMID- 31913730 OWN - NLM STAT- MEDLINE DCOM- 20201124 LR - 20240330 IS - 1521-0464 (Electronic) IS - 1071-7544 (Print) IS - 1071-7544 (Linking) VI - 27 IP - 1 DP - 2020 Dec TI - Study on the cellular internalization mechanisms and in vivo anti-bone metastasis prostate cancer efficiency of the peptide T7-modified polypeptide nanoparticles. PG - 161-169 LID - 10.1080/10717544.2019.1709923 [doi] AB - 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. FAU - Gu, Yongwei AU - Gu Y AD - Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China. AD - School of Pharmacy, Second Military Medical University, Shanghai, China. FAU - Chen, Xinmei AU - Chen X AD - Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China. FAU - Zhang, Haiyan AU - Zhang H AD - Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China. FAU - Wang, Heyi AU - Wang H AD - Department of Pharmacy, Inner Mongolia Medical University, Huhhot, China. FAU - Chen, Hang AU - Chen H AD - Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China. FAU - Huang, Sifan AU - Huang S AD - Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China. FAU - Xu, Youfa AU - Xu Y AD - Shanghai Wei Er Biopharmaceutical Technology Co., Ltd, Shanghai, China. FAU - Zhang, Yuansheng AU - Zhang Y AD - Shanghai Wei Er Biopharmaceutical Technology Co., Ltd, Shanghai, China. FAU - Wu, Xin AU - Wu X AD - School of Pharmacy, Second Military Medical University, Shanghai, China. AD - Shanghai Wei Er Biopharmaceutical Technology Co., Ltd, Shanghai, China. FAU - Chen, Jianming AU - Chen J AD - Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China. AD - Department of Pharmacy, Inner Mongolia Medical University, Huhhot, China. LA - eng PT - Journal Article PL - England TA - Drug Deliv JT - Drug delivery JID - 9417471 RN - 0 (Membrane Proteins) RN - 0 (Peptide Fragments) RN - 0 (Pmepa1 protein, mouse) RN - 0 (peptide T (4-8)) RN - 106362-33-8 (Peptide T) RN - 30KYC7MIAI (Aspartic Acid) RN - 3WJQ0SDW1A (Polyethylene Glycols) RN - 94ZLA3W45F (Arginine) RN - K848JZ4886 (Cysteine) SB - IM MH - Animals MH - Arginine MH - Aspartic Acid MH - Bone Neoplasms/*prevention & control/*secondary MH - Cell Line, Tumor MH - Cell Movement MH - Cell Survival MH - Cysteine MH - Genetic Vectors/*chemistry/*pharmacology MH - Male MH - Membrane Proteins/genetics MH - Mice MH - Mice, Inbred BALB C MH - Nanoparticles/chemistry MH - Particle Size MH - Peptide Fragments MH - Peptide T MH - Polyethylene Glycols/chemistry MH - Prostatic Neoplasms/*genetics/*pathology MH - Tumor Burden PMC - PMC6968257 OTO - NOTNLM OT - Gene therapy OT - administration safety OT - anti-tumor effect OT - bone-metastases prostate cancer OT - cellular internalization mechanisms EDAT- 2020/01/09 06:00 MHDA- 2020/11/25 06:00 PMCR- 2020/01/08 CRDT- 2020/01/09 06:00 PHST- 2020/01/09 06:00 [entrez] PHST- 2020/01/09 06:00 [pubmed] PHST- 2020/11/25 06:00 [medline] PHST- 2020/01/08 00:00 [pmc-release] AID - 1709923 [pii] AID - 10.1080/10717544.2019.1709923 [doi] PST - ppublish SO - Drug Deliv. 2020 Dec;27(1):161-169. doi: 10.1080/10717544.2019.1709923.