Journal
CARBOHYDRATE POLYMERS
Volume 326, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2023.121577
Keywords
Targeting delivery; Cyclodextrin; Methotrexate; Host-guest amphiphiles; Carbonic anhydrase IX targeting
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In this study, a drug delivery system based on self-assembly was developed to deliver anticancer drugs to tumor tissues with targeted effects. The system showed inhibitory effects on cancer cells while minimizing toxic effects on normal cells. Additionally, the system demonstrated disintegration and drug release under specific conditions.
It remains a critical issue to deliver anticancer drugs to tumor tissues and reducing the toxic effects on normal tissues. The drug delivery system (DDS) based on self-assembly provides a multi-functional way for drug delivery. In this work, a supramolecular host (L-CD) with targeting function based on a beta-cyclodextrin (beta-CD) backbone was synthesized with carbonic anhydrase IX (CAIX) overexpressed on tumor cells as a target, and the methotrexate prodrug (MTX-SS-Ad) modified by adamantane and disulfide bond was prepared to be used as the guest. The amphiphilic complex was prepared between L-CD and MTX-SS-Ad through host-guest interactions and could further self-assemble into supramolecular nanoparticles (SNPs) with active targeting and stimulus release functions. The interaction between host and guest was investigated by UV, NMR, IR, XRD and TGA. The characteristic of SNPs was observed by DLS and TEM. Throng the study of molecular docking, in vitro inhibition, cell uptake experiments, and western blotting, SNPs have showed CAIX inhibitory effects both inside and outside the cells. The in vitro release experiments indicated that SNPs can undergo disintegration and release drugs under acidic and GSH conditions. Moreover, SNP can effectively inhibit the proliferation of cancer cells without generating additional toxic side effects on normal cells. So, we provide a strategy of bifunctional drug delivery system with targeting and glutathione-responsivity for effective tumor therapy.
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