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

Research output: Contribution to journalArticle

9 Citations (Scopus)

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/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.

Original languageEnglish
Pages (from-to)2131-2141
Number of pages11
JournalAdvanced healthcare materials
Volume5
Issue number16
DOIs
Publication statusPublished - Aug 24 2016

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Doxorubicin
Tumors
Ligands
Neoplasms
Medical nanotechnology
Therapeutics
Nanomedicine
Aptitude
Tumor Burden
Sulfhydryl Compounds
Nanoparticles
Copolymers
Modulation
Plasmas
Growth
Pharmaceutical Preparations
Trastuzumab

Keywords

  • intratumoral distribution
  • ligand density
  • multistage magnetic targeting
  • synergistic targeting

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biomaterials
  • Pharmaceutical Science

Cite this

Synergistic Combination of Multistage Magnetic Guidance and Optimized Ligand Density in Targeting a Nanoplatform for Enhanced Cancer Therapy. / Chiang, Chih Sheng; Shen, Yi Shang; Liu, Jun Jen; Shyu, Woei Cherng; Chen, San Yuan.

In: Advanced healthcare materials, Vol. 5, No. 16, 24.08.2016, p. 2131-2141.

Research output: Contribution to journalArticle

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