Dual Responsive Magnetic Drug Delivery Nanomicelles with Tumor Targeting for Enhanced Cancer Chemo/Magnetothermal Synergistic Therapy

Abstract

Jianmeng Zhu,1,* Yimin Yang,2,3,* Jian Wang,1 Wenzhong Hong,1 Yiping Li,1 Zhen Wang,2 Kaiqiang Li2 1Clinical Laboratory of Chun’an First People’s Hospital, Zhejiang Provincial People’s Hospital Chun’an Branch, Hangzhou, Zhejiang, People’s Republic of China; 2Laboratory Medicine Center, Allergy Center, Department of Transfusion Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 3College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhen Wang; Kaiqiang Li, Laboratory Medicine Center, Allergy Center, Department of Transfusion Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, 158 Shangtang Road, Hangzhou, Zhejiang, 310014, People’s Republic of China, Tel/Fax [phone], Email [email protected]; [email protected]: Stimulus-responsive nanocarrier systems are promising in cancer treatment. They improve drug stability and facilitate controlled drug release. However, single-responsive nanocarriers still face insufficient tumor targeting and low efficacy.Methods: In this study, we synthesized folate-modified DSPE-PEOz nanomicelles with PEG chains and loaded them with magnetic iron particles and doxorubicin (DOX). Folic acid (FA) was employed as a ligand to target cancer cells actively. The nanomicelles are biocompatible and acid-sensitive drug carriers. Magnetic field-responsive nanoparticles enable moderately controlled magnetothermal therapy of tumors regardless of tumor location. The pH/magnetic field dual-responsive nanomicelles shed their PEG layer in response to tumor tissue acidity and react to magnetic fields through magnetothermal effects.Results: In vitro and in vivo experiments demonstrated that the nanomicelles could efficiently target cancer cells, release drugs in response to pH changes, and enhance drug uptake through magnetothermal effects.Discussion: The dual-responsive magnetic nanomicelles are expected to enhance the anti-cancer efficacy of chemo/magnetothermal synergistic therapy. Keywords: nanomicelles, synergistic therapy, stimulus-responsive, tumor targeting, Chemo/magnetothermal

Keywords

• nanomicelles
• synergistic therapy
• stimulus-responsive
• tumor targeting
• chemo/magnetothermal