Pillar[5]arene based glyco-targeting nitric oxide nanogenerator for hyperthermia-induced triple-mode cancer therapy

• Published in: Journal of colloid and interface science Vol. 615; pp. 386 - 394
• Main Authors: Wang, Yang, Wen, Yafei, Qu, Yun, Pei, Zhichao, Pei, Yuxin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2022
• Subjects: Alkyl radical therapy; Calixarenes; Cell Line, Tumor; Gas therapy; Gold - chemistry; Hyperthermia, Induced; Nanotubes - chemistry; Neoplasms; Nitric Oxide; Nitric oxide nanogenerator; Phototherapy; Photothermal therapy; Pillararene; Quaternary Ammonium Compounds; Photothermal therapy; Alkyl radical therapy; Gas therapy; Pillararene; Nitric oxide nanogenerator
• ISSN: 0021-9797; 1095-7103
• DOI: 10.1016/j.jcis.2022.01.189

The supramolecular complex between amino pillar[5]arene and galactose derivative modified glyco-targeting NO nanogenerator was designed and constructed, which generated hyperthermia to induce triple-mode therapy of photothermal/gas/alkyl radical therapy upon 808 nm NIR irradiation. [Display omitted] Nitric oxide (NO)-mediated gas therapy (GT) and alkyl radical (R•) therapy (ART) are emerging cancer therapy modes, and multi-mode therapy has been recognized as an attractive strategy for enhancing anti-cancer efficacy. In this work, a thermal-responsive R• initiator 2,2′-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIBI)-loaded glycol-targeting NO nanogenerator was constructed by first the covalent conjugation of thermal-responsive NO donor of S-nitrosothiols (RSNO) on the surface of mesoporous silica-coated gold nanorods (AuNRs@MSN), then the coating of a supramolecular complex of amino pillar[5]arene (NP5) and galactose derivative (G), and finally the loading of AIBI. The glycol-targeting NO nanogenerator demonstrated specific targeting ability to HepG2 cells owing to the recognition between galactose residues and asialoglycoprotein receptors (ASGPR). Specially, upon 808 nm near-infrared (NIR) irradiation, the AIBI-loaded NO nanogenerator generated hyperthermia to achieve photothermal therapy (PTT), and further GT and ART resulted from the thermal responsiveness of RSNO and AIBI, respectively. In vitro experiments revealed that the AIBI-loaded glyco-targeting NO nanogenerator had good biocompatibility and exhibited effective inhibition to the proliferation of HepG2 cells. This work provides a novel way to supramolecular hybrid drug delivery systems for triple-mode targeting therapy of PTT/GT/ART.