Synergistic Combination of Multistage Magnetic Guidance and Optimized Ligand Density in Targeting a Nanoplatform for Enhanced Cancer Therapy

Chih Sheng Chiang, Yi Shang Shen, Jun Jen Liu, Woei Cherng Shyu, San-Yuan Chen*

*此作品的通信作者

研究成果: Article同行評審

29 引文 斯高帕斯(Scopus)

摘要

A new therapeutic strategy of combining multistage short-term magnetic guidance with optimized ligand-mediated targeting in a newly developed nanodelivery system is investigated to promote accumulation and modulate intratumoral distribution behavior of the nanocarriers for enhanced tumor therapy. The multifunctional magnetic nanocarriers (MNCs) composed of single-component thiol-functionalized PVA/PMASH copolymer and superparamagnetic nanoparticles are developed for providing tunable dual-targeting ability and simultaneously modulating pH-responsive on/off drug release. Results show that plasma doxorubicin (Dox) concentration of the mice treated with Trastuzumab (Tra)-targeted Dox-MNCs can be rapidly decreased by applying dual-targeting treatment. More importantly, cooperative modulation of magnetic targeting and Tra density on the nanocarrier significantly optimize intratumoral distribution and enhance the utilization rate of nanomedicines within tumor to inhibit tumor growth. The mice treated with 2T-Dox-MNCs + multistage magnetic targeting (MT) (2 h d−1) show 7.63-fold, 3.25-fold, and 2.7-fold reduction in HER2-positive tumor volume compared to Dox-MNCs, 2T-Dox-MNCs, and 2T-Dox-MNCs + single MT (12 h). The synergistic dual-targeting approach represents a major paradigm advance in tumor treatment and nanocarrier design in preclinical application.

原文English
頁(從 - 到)2131-2141
頁數11
期刊Advanced Healthcare Materials
5
發行號16
DOIs
出版狀態Published - 24 8月 2016

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