Title: Synergistic Combination of Multistage Magnetic Guidance and Optimized Ligand Density in Targeting a Nanoplatform for Enhanced Cancer Therapy
Authors: Chiang, Chih-Sheng
Shen, Yi-Shang
Liu, Jun-Jen
Shyu, Woei-Cherng
Chen, San-Yuan
Department of Materials Science and Engineering
Keywords: intratumoral distribution;ligand density;multistage magnetic targeting;synergistic targeting
Issue Date: 24-Aug-2016
Abstract: 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/PMA(SH) 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.
URI: http://dx.doi.org/10.1002/adhm.201600479
ISSN: 2192-2640
DOI: 10.1002/adhm.201600479
Volume: 5
Issue: 16
Begin Page: 2131
End Page: 2141
Appears in Collections:Articles