| Affiliation: | 1. Hongqiao International Institute of Medicine, Tongren Hospital and State Key Laboratory of Oncogenes and Related Genes, Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, 200025 China;2. Hongqiao International Institute of Medicine, Tongren Hospital and State Key Laboratory of Oncogenes and Related Genes, Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, 200025 China Department of Pharmacy, Shanghai Ninth People's Hospital, SJTU-SM, Shanghai, 200011 China;3. Department of General Surgery, Tongren Hospital, SJTU-SM, Shanghai, 200336 China;4. Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY, 14260 USA;5. Institute of Interdisciplinary Integrative Biomedical Research, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203 China |
| Abstract: | Living cell-based drug delivery systems (LC-DDSs) are limited by adverse interactions between drugs and carrier cells, typically drug-induced toxicity to carrier cells and restriction of carrier cells on drug release. Here, a method is established to adsorb nanocarriers externally to living cells, thereby reducing cytotoxicity caused by drug uptake and realizing improved drug release at the disease site. It is found that a divalent metal ion-phenolic network (MPN) affords adhesion of poly (lactic-co-glycolic acid) nanoparticles onto macrophage (Mφ) surfaces with minimized intracellular uptake and no negative effect on cell proliferation. On this basis, an Mφ-DDS with doxorubicin-loaded nanoparticles on cell surface (DOX-NP@Mφ) is constructed. Compared to intracellular loading via endocytosis, this method well-maintains bioactivity (viability and migration chemotaxis) of the carrier cell. By virtue of the photothermal effect of MPN at the tumor site, DOX-NP-associated vesicles are liberated for improved chemotherapy. This facile, benign, and efficient method (ice bath, 2 min) for extracellular nanoparticle attachment and minimizing intracellular uptake provides a platform technology for LC-DDS development. |
