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iRGD and TGN co-modified PAMAM for multi-targeted delivery of ATO to gliomas.
Biochem Biophys Res Commun. 2020 Jun 18; 527(1):117-123.BB

Abstract

A poly(amidoamine) dendrimer (PAMAM, G5) based drug delivery system was developed for the treatment of glioma. PAMAM was modified with polyethylene glycol (PEG) to improve its in vivo stability and reduce immunogenicity. Further, the internalized RGD (iRGD) recognition ligand of the integrin αvβ3 receptor and the blood-brain barrier (BBB)-targeting group TGN were introduced. Arsenic trioxide (ATO) was loaded into the internal cavity through electrostatic interactions to form iRGD/TGN-PEG-PAMAM-ATO. The drug delivery system of iRGD/TGN dual-modified PAMAM, which entrapped ATO, had a high entrapment efficiency of approximately 71.92% ± 1.17% and displayed sustainable acid-dependent drug release. Assessment of antiglioma effects revealed that survival rate was significantly higher in the iRGD/TGN comodified group than in the other groups. Overall, iRGD/TGN-based dual targeting by combining nanocarriers and targeting technology increased the amount of drug that crossed BBB, thus achieving targeted enrichment and activation of the drug in tumor tissue. This activation ultimately increased therapeutic effects and reduced side effects of ATO. This strategy using a multistep-targeted delivery system shows great promise for targeted glioma therapy.

Authors+Show Affiliations

College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China.College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China.Department of Pharmacy, The First People's Hospital of Fuyang Hangzhou, Hangzhou, Zhejiang, 311400, PR China.College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China.College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China.College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China.Libraries of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou, 310053, China.College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China. Electronic address: lifanzhu@zcmu.edu.cn.College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China. Electronic address: jgpiao@zcmu.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32446354

Citation

Shi, Xiaowei, et al. "IRGD and TGN Co-modified PAMAM for Multi-targeted Delivery of ATO to Gliomas." Biochemical and Biophysical Research Communications, vol. 527, no. 1, 2020, pp. 117-123.
Shi X, Ma R, Lu Y, et al. IRGD and TGN co-modified PAMAM for multi-targeted delivery of ATO to gliomas. Biochem Biophys Res Commun. 2020;527(1):117-123.
Shi, X., Ma, R., Lu, Y., Cheng, Y., Fan, X., Zou, J., Zheng, H., Li, F., & Piao, J. G. (2020). IRGD and TGN co-modified PAMAM for multi-targeted delivery of ATO to gliomas. Biochemical and Biophysical Research Communications, 527(1), 117-123. https://doi.org/10.1016/j.bbrc.2020.04.064
Shi X, et al. IRGD and TGN Co-modified PAMAM for Multi-targeted Delivery of ATO to Gliomas. Biochem Biophys Res Commun. 2020 Jun 18;527(1):117-123. PubMed PMID: 32446354.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - iRGD and TGN co-modified PAMAM for multi-targeted delivery of ATO to gliomas. AU - Shi,Xiaowei, AU - Ma,Rui, AU - Lu,Yanping, AU - Cheng,Ying, AU - Fan,Xudong, AU - Zou,Jiafeng, AU - Zheng,Hongyue, AU - Li,Fanzhu, AU - Piao,Ji-Gang, Y1 - 2020/04/28/ PY - 2020/02/16/received PY - 2020/03/13/revised PY - 2020/04/13/accepted PY - 2020/5/25/entrez PY - 2020/5/25/pubmed PY - 2020/5/25/medline KW - Drug delivery system KW - Glioblastoma KW - Glioma KW - Internalized RGD KW - TGN SP - 117 EP - 123 JF - Biochemical and biophysical research communications JO - Biochem. Biophys. Res. Commun. VL - 527 IS - 1 N2 - A poly(amidoamine) dendrimer (PAMAM, G5) based drug delivery system was developed for the treatment of glioma. PAMAM was modified with polyethylene glycol (PEG) to improve its in vivo stability and reduce immunogenicity. Further, the internalized RGD (iRGD) recognition ligand of the integrin αvβ3 receptor and the blood-brain barrier (BBB)-targeting group TGN were introduced. Arsenic trioxide (ATO) was loaded into the internal cavity through electrostatic interactions to form iRGD/TGN-PEG-PAMAM-ATO. The drug delivery system of iRGD/TGN dual-modified PAMAM, which entrapped ATO, had a high entrapment efficiency of approximately 71.92% ± 1.17% and displayed sustainable acid-dependent drug release. Assessment of antiglioma effects revealed that survival rate was significantly higher in the iRGD/TGN comodified group than in the other groups. Overall, iRGD/TGN-based dual targeting by combining nanocarriers and targeting technology increased the amount of drug that crossed BBB, thus achieving targeted enrichment and activation of the drug in tumor tissue. This activation ultimately increased therapeutic effects and reduced side effects of ATO. This strategy using a multistep-targeted delivery system shows great promise for targeted glioma therapy. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/32446354/iRGD_and_TGN_co-modified_PAMAM_for_multi-targeted_delivery_of_ATO_to_gliomas L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(20)30790-7 DB - PRIME DP - Unbound Medicine ER -
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