Quercetin and doxorubicin co-delivery using mesoporous silica nanoparticles enhance the efficacy of gastric carcinoma chemotherapy

• Published in: International journal of nanomedicine Vol. 13; pp. 5113 - 5126
• Main Authors: Fang, Jian, Zhang, Shangwu, Xue, Xiaofeng, Zhu, Xinguo, Song, Shiduo, Wang, Bin, Jiang, Linhua, Qin, Mingde, Liang, Hansi, Gao, Ling
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2018; Taylor & Francis Ltd; Dove Medical Press
• Subjects: Analysis; Animals; Anthracyclines; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism; Biomedical materials; Cancer; Cancer therapies; Cancer treatment; Carcinoma; Cell adhesion & migration; Cell Death; Cell Line, Tumor; Chemotherapy; co-delivery; Colloids; Deoxyribonucleic acid; DNA; doxorubicin; Doxorubicin - administration & dosage; Doxorubicin - therapeutic use; Drug Delivery Systems; Drug Liberation; Drug resistance; Fibroblasts; Gastric cancer; gastric carcinoma; Growth factors; Humans; Hyaluronic acid; Laboratory animals; Male; Medical prognosis; Metastasis; Mice, Inbred BALB C; Microbial drug resistance; Nanoparticles; Nanoparticles - chemistry; Nanoparticles - ultrastructure; Original Research; Particle Size; Porosity; Quantum Dots - chemistry; quercetin; Quercetin - administration & dosage; Quercetin - therapeutic use; Silicon dioxide; Silicon Dioxide - chemistry; Spheroids, Cellular - drug effects; Spheroids, Cellular - metabolism; Spheroids, Cellular - pathology; Static Electricity; Stomach cancer; Stomach Neoplasms - drug therapy; Stomach Neoplasms - pathology; Surgery; Time Factors; Tissue Distribution - drug effects; Treatment Outcome; Tumor Burden - drug effects; Tumors; Wnt Proteins - metabolism; United States > US; China; co-delivery; quercetin; doxorubicin; gastric carcinoma; chemotherapy
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S170862

Effective gastric carcinoma (GC) chemotherapy is subject to many in vitro and in vivo barriers, such as tumor microenvironment and multidrug resistance. Herein, we developed a hyaluronic acid (HA)-modified silica nanoparticle (HA-SiLN/QD) co-delivering quercetin and doxorubicin (DOX) to enhance the efficacy of GC therapy (HA-SiLN/QD). The HA modification was done to recognize overexpressed CD44 receptors on GC cells and mediate selective tumor targeting. In parallel, quercetin delivery decreased the expression of Wnt16 and P-glycoprotein, thus remodeling the tumor microenvironment and reversed multidrug resistance to facilitate DOX activity. Experimental results demonstrated that HA-SiLN/QD was nanoscaled particles with preferable stability and sustained release property. In vitro cell experiments on SGC7901/ADR cells showed selective uptake and increased DOX retention as compared to the DOX mono-delivery system (HA-SiLN/D). In vivo anticancer assays on the SGC7901/ADR tumor-bearing mice model also revealed significantly enhanced efficacy of HA-SiLN/QD than mono-delivery systems (HA-SiLN/Q and HA-SiLN/D).