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Synergistic Combination of Multistage Magnetic Guidance and Optimized Ligand Density in Targeting a Nanoplatform for Enhanced Cancer Therapy
Author(s) -
Chiang ChihSheng,
Shen YiShang,
Liu JunJen,
Shyu WoeiCherng,
Chen SanYuan
Publication year - 2016
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201600479
Subject(s) - nanocarriers , doxorubicin , cancer research , superparamagnetism , drug delivery , materials science , distribution (mathematics) , targeted therapy , pharmacology , chemistry , nanotechnology , cancer , medicine , chemotherapy , magnetic field , mathematical analysis , physics , magnetization , mathematics , quantum mechanics
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.

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