Molecular imprinted S-nitrosothiols nanoparticles for nitric oxide control release as cancer target chemotherapy

Liu, TW (Liu, Tuanwei)^[ 1 ] ; Qiao, ZY (Qiao, Zhenyun)^[ 1 ] ; Wang, JL (Wang, Jilan)^[ 3 ] ; Zhang, P (Zhang, Ping)^[ 1 ] ; Zhang, ZD (Zhang, Zhide)^[ 1 ] ; Guo, DS(Guo, Dian-Shun)^[ 1 ] ; Yang, XL (Yang, Xinlin)^[ 2 ]

COLLOIDS AND SURFACES B-BIOINTERFACES, 2019, 173: 356-365

DOI: 10.1016/j.colsurfb.2018.09.078

Abstract

It is the goal for the development of cancer target chemotherapy with specific recognition, efficient killing the tumor cells and tissues to avoid the intolerable side effects. Molecular imprinted polymer (MIPs) nanoparticles could introduce kinds of specific bio-markers (template molecules) into the nanoparticles with the subsequent removal, leaving special holes in the structure with predictable recognition specificity with cells. Herein, we design and synthesize a kind of sialic acid (SA) over-expressed tumor target hollow double-layer imprinted polymer nanoparticles with S-nitrosothiols for nitric oxide (NO)-releasing as chemotherapy. Equilibrium/selective bindings properties and probe experimental results implies that the MIPs have an intelligently selective binding to cancer cells featuring high levels of SA glyans, providing precondition for the disulfide polymer assisted cell uptake, intracellular GSH induced decomposition and rapid NO-releasing. Cytotoxicity assay with kinds of cells demonstrates the intelligent in vitro SA over-expressed tumor cells targeting recognition, intracellular delivery and cytotoxicity. In vivo bio-distribution in tumor sites and major organs, significant suppression of tumor growth, tumor-bearing mice survival unit, and the systemic toxicity investigation experiments confirm the effective chemotherapy of the S-nitrosothiols MIPs nanoparticles for the target recognition and the controlled NO release for tumor treatment comparing to the results with S-nitrosothiols CPs as delivery system. The inevitable small amount of NO leakage from S-nitrosothiols MIPs would take part in normal physiological activities and not cause serious side effects. For the first time, this kind of nitric oxide based chemotherapy and molecular-imprinting cell recognition technique both in vitro and in vivo, might provide a solution for accurate therapy to various forms of cancer with specific markers and avoi7d the intolerable side effects of the traditional chemotherapy treatment.