Dual-Targeting to Cancer Cells and M2 Macrophages via Biomimetic Delivery of Mannosylated Albumin Nanoparticles for Drug-Resistant Cancer Therapy

5 years ago

Dual-Targeting to Cancer Cells and M2 Macrophages via Biomimetic Delivery of Mannosylated Albumin Nanoparticles for Drug-Resistant Cancer Therapy

Yongzhuo Huang, Tingting Lin, Yifei Duan, Binfan Chen, Yisi Tang, Pengfei Zhao, Meng Zhang, Aihua Wu, Zhenzhen Pan, Jinyu Wang, Weimin Yin

Multidrug resistance (MDR) is an issue that is not only related to cancer cells but also associated with the tumor microenvironments. MDR involves the complicated cancer cellular events and the crosstalk between cancer cells and their surroundings. Ideally, an effective system against MDR cancer should take dual action on both cancer cells and tumor microenvironments. The authors find that both the drug-resistant colon cancer cells and the protumor M2 macrophages highly express two nutrient transporters, i.e., secreted protein acidic and rich in cysteine (SPARC) and mannose receptors (MR). By targeting SPARC and MR, a system can act on both cancer cells and M2 macrophages. Herein the authors develop a mannosylated albumin nanoparticles with coencapsulation of different drugs, i.e., disulfiram/copper complex (DSF/Cu) and regorafenib (Rego). The results show that combination therapy of DSF/Cu and Rego efficiently inhibits the growth of drug-resistant colon tumor, and the combination has not been reported yet for use in anticancer treatment. The system significantly improves the treatment outcomes in the animal model bearing drug-resistant tumors. The therapeutic mechanisms involve enhanced apoptosis, upregulation of intracellular ROS, anti-angiogenesis, and tumor-associated macrophage “re-education.” This strategy is characterized by dual targeting to and the simultaneous action on cancer cells and M2 macrophages, with biomimetic codelivery of a novel drug combination. Multidrug resistance (MDR) is a complex of various events involving not only the cancer cells but also their surroundings (tumor microenvironments). The authors develop the “one stone two birds” strategy to overcome MDR by using a mannosylated albumin nanoparticulate codelivery system to dual-target the cancer cells and M2 macrophages, both of which overexpress mannose receptors and the albumin-binding protein—secreted protein acidic and rich in cysteine.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/adfm.201700403