Dataset Information

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

ABSTRACT:

Background

Effective gastric carcinoma (GC) chemotherapy is subject to many in vitro and in vivo barriers, such as tumor microenvironment and multidrug resistance.

Materials and methods

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.

Results

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).

Conclusion

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).

SUBMITTER: Fang J

PROVIDER: S-EPMC6135215 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Fang Jian J Zhang Shangwu S Xue Xiaofeng X Zhu Xinguo X Song Shiduo S Wang Bin B Jiang Linhua L Qin Mingde M Liang Hansi H Gao Ling L

International journal of nanomedicine 20180906

<h4>Background</h4>Effective gastric carcinoma (GC) chemotherapy is subject to many in vitro and in vivo barriers, such as tumor microenvironment and multidrug resistance.<h4>Materials and methods</h4>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 targ ...[more]

PMID: 30233175

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Project description:Tunable glutathione (GSH)-sensitive hollow mesoporous silica nanoparticles (HMSiO2 NPs) were developed using a structural difference-based selective etching strategy. These organosilica hollow nanoparticles contained disulfide linkages (S-S) in the outer shell which were degraded by GSH. The particles were compared with their nonGSH-sensitive tetraethyl orthosilicate (TEOS) HMSiO2 counterparts in terms of their synthesis method, characterization, doxorubicin (DOX) release profile, and in vitro cytotoxicity in MCF-7 breast cancer cells. Transmission electron microscopy (TEM) of the particles indicated that the fabricated HMSiO2 NPs had an average diameter of 130?±?5?nm. Thermogravimetric analysis (TGA) revealed that GSH-sensitive particles had approximately 5.3% more weight loss than TEOS HMSiO2 NPs. Zeta potential of these redox-responsive particles was -23?±?1?mV at pH?6 in deionized (DI) water. Nitrogen adsorption-desorption isotherm revealed that the surface area of the hollow mesoporous nanoreservoirs was roughly 446?±?6?m2?g-1 and the average diameter of the pores was 2.3?±?0.5?nm. TEM images suggest that the nanoparticles started to lose mass integrity from Day 1. The particles showed a high loading capacity for DOX (8.9?±?0.5%) as a model drug, due to the large voids existing in the hollow structures. Approximately 58% of the incorporated DOX released within 14?days in phosphate buffered saline (PBS) at pH?6 and in the presence of 10?mM of GSH, mimicking intracellular tumor microenvironment while release from TEOS HMSiO2 NPs was only c.a. 18%. The uptake of these hollow nanospheres by MCF-7 cells and RAW 264.7 macrophages was evaluated using TEM and confocal microscopy. The nanospheres were shown to accumulate in the endolysosomal compartments after incubation for 24?h with the maximum uptake of c.a. 2.1?±?0.3% and 5.2?±?0.4%, respectively. Cytotoxicity of the nanospheres was investigated using CCK-8 assay. Results indicate that intact hollow particles (both GSH-sensitive and TEOS HMSiO2 NPs) were nontoxic to MCF-7 cells after incubation for 24?h within the concentration range of 0-1000??g?ml-1. DOX-loaded GSH-sensitive nanospheres containing 6??g?ml-1 of DOX killed c.a. 51% of MCF-7 cells after 24?h while TEOS HMSiO2 NPs killed c.a. 20% with the difference being statistically significant. Finally, cytotoxicity data in RAW 264.7 macrophages and NIH 3?T3 fibroblasts shows that intact GSH-sensitive HMSiO2 NPs did not show any toxic effects on these cells with the concentrations equal or <125??g?ml-1.

Dataset Information

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

Background

Materials and methods

Results

Conclusion

Publications

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

Similar Datasets

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