Glyconanoparticles with Activatable Near-Infrared Probes for Tumor-Cell Imaging and Targeted Drug Delivery

• Published in: International journal of nanomedicine Vol. 17; pp. 1567 - 1575
• Main Authors: Chi, Guanyu, Lv, Yinghua, Chao, Shuang, Hou, Chenxi, Pei, Yuxin, Pei, Zhichao
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2022; Dove; Dove Medical Press
• Subjects: Cancer; Chemotherapy; Drug delivery systems; Drugs; Fluorescence; gsh-responsive; Investigations; Lactose; near-infrared probes; Original Research; polydopamine; targeted drug delivery; tumor cell imaging; Vehicles; China; targeted drug delivery; near-infrared probes; tumor-cell imaging; polydopamine; GSH-responsive
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S337082

Multifunctional nanocarriers based on tumor targeting and intracellular monitoring have received much attention and been a subject of intensive study by researchers in recent years. In this study, we report multifunctional glyconanoparticles with activatable near-infrared probes for tumor imaging and targeted drug delivery. Disulfide-functionalized dicyanomethylene-4 -pyran (DCM-SS-NH ) and amino-functionalized lactose were modified and loaded onto the surfaces of polydopamine nanoparticles (NPs) by Michael addition or Schiff-base reaction as GSH stimulation-responsive fluorescent probes and tumor-targeting moieties, respectively. Doxorubicin (DOX), a model anticancer drug, was loaded onto polydopamine through π-π interactions directly to prepare multifunctional PLDD (PDA@Lac/DCM/DOX) NPs. Experimental results showed that PLDD NPs had been successfully prepared. DCM, the fluorescence of which was quenched in PLDD NPs, was able to restore red fluorescence in a solution with a GSH concentration of 5 mM. The amount of DOX released from PLDD NPs was 44% over 72 hours in a weak-acid environment (pH 5). The results of CLSM and flow cytometry indicated that the PLDD NPs had good HepG2-targeting ability due to the special recognition between lactose derivative of NPs and overexpressed asialoglycoprotein receptors on HepG2 cell membrane. More importantly, the disulfide bond of DCM-SS-NH was broken by the high concentration of GSH inside cancer cells, activating the near-infrared fluorescence probe DCM for cancer-cell imaging. MTT assays indicated that PLDD NPs exhibited higher anticancer efficiency for HepG2 cells and had reduced side effects on normal cells compared with free DOX. The fluorescence of modified DCM loaded onto PLDD NPs is able to be restored in the high-concentration GSH environment within cancer cells, while improving the effectiveness of chemotherapy with reduced side effects. It provides a good example of integration of tumor imaging and targeted drug delivery.