title: Synergistic Combination of Multistage Magnetic Guidance and Optimized Ligand Density in Targeting a Nanoplatform for Enhanced Cancer Therapy.
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.
authors.affiliation: Department of Materials Science and Engineering, National Chiao Tung University, Hsinchu City, 30010, Taiwan, Republic of China.
authors.forename: Chih-Sheng
authors.initials: CS
authors.lastname: Chiang
authors.affiliation: Division of Orthopaedics, Department of Surgery, Far Eastern Memorial Hospital, New Taipei City, 220, Taiwan, Republic of China.|Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan, Republic of China.
authors.forename: Yi-Shang
authors.initials: YS
authors.lastname: Shen
authors.affiliation: School of Medical Laboratory Science and Biotechnology, Taipei Medical University, Taipei City, 110, Taiwan, Republic of China.
authors.forename: Jun-Jen
authors.initials: JJ
authors.lastname: Liu
authors.affiliation: Graduate Institute of Immunology, China Medical University, Taichung City, 40402, Taiwan, Republic of China.
authors.forename: Woei-Cherng
authors.initials: WC
authors.lastname: Shyu
authors.affiliation: Department of Materials Science and Engineering, National Chiao Tung University, Hsinchu City, 30010, Taiwan, Republic of China.
authors.forename: San-Yuan
authors.initials: SY
authors.lastname: Chen
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006801:Humans; D060526:Magnetic Fields; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D004337:Drug Carriers; D004317:Doxorubicin
keywords: intratumoral distribution; ligand density; multistage magnetic targeting; synergistic targeting