Preparation and characterization of doxorubicin and siRNA co-loaded CLMSNs and study on anti-multidrug-resistant tumor cells
- VernacularTitle:共载阿霉素与小干扰RNA的脂质介孔硅纳米粒的制备表征及抗多药耐药肿瘤细胞研究
- Author:
Mengwei ZHANG
1
,
2
;
Shuoye YANG
1
,
2
;
Yanan YANG
1
,
2
;
Zhenwei WANG
1
,
2
;
Lingbo QU
1
Author Information
1. College of Biological Engineering，Henan University of Technology，Zhengzhou 450001，China
2. Zhengzhou Key Lab of Biomedical Functional Molecules，Zhengzhou 450001，China
- Publication Type:Journal Article
- Keywords:
mesoporous silica;
siRNA;
doxorubicin;
anti-
- From:
China Pharmacy
2022;33(23):2880-2885
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To prepare lipid-coated mesoporous silica nanoparticles （CLMSNs） co-loaded with doxorubicin （DOX） and siRNA （CLMSNs-SS-NH2@DOX/siRNA），and to characterize it and study anti-multidrug-resistant tumor cells. METHODS MSNs-SS-NH2@DOX was prepared on the basis of mesoporous silica （MSNs），covered with cationic liposomes （CLs） to synthesize CLMSNs-SS-NH2@DOX，and then obtain CLMSNs-SS-NH2@DOX/siRNA by co-loading with siRNA. The particle size and Zeta potential of the preparation were determined，and its micromorphology was observed； differential scanning calorimetry，X-ray diffraction，infrared spectroscopy and physical adsorption analysis were conducted. The in vitro release of DOX from the preparation was determined under different pH conditions （pH5.0，pH7.4） and different glutathione concentrations （0，2，5， 10 mmol/L）. The effects of this preparation on the uptake，migration，apoptosis，cycle and P-glycoprotein （P-gp） expression of MCF-7/ ADR in DOX-resistant breast cancer cells were investigated. RESULTS CLMSNs-SS-NH2@DOX/siRNA had a clear core-shell structure，obvious lipid membrane layer，particle size of （197.63±3.75） nm，Zeta potential of （20.64±0.98） mV，and with good physical and chemical properties. In vitro release results showed that CLMSNs-SS-NH2@DOX/siRNA possessed good pH/reduction double-response. The results of cell experiment showed that after intervened with CLMSNs-SS-NH2@DOX/siRNA，the fluorescence intensity of MCF-7/ADR cells was significantly enhanced，the migration rate and P-gp expression level were significantly reduced， while total proportion of apoptosis and that of G0/G1 phase were significantly increased （P＜0.05）. CONCLUSIONS In this study， DOX and siRNA co-loaded CLMSNs-SS-NH2@DOX/siRNA is prepared successfully， which has good physical and chemical properties， pH/reduction double-response properties. It can reverse the multidrug resistance of MCF-7/ADR cells by down-regulation of P-gp expression.
