Objective: To develop a co-delivery system based on hollow mesoporous silica nanoparticles(HMSN), and explore the effect of this system in reversing multiple drug resistance in ovarian cancer cell SKOV-3/ADR. Methods: HMSN was selected as the nanocarriers, with-COOH modified on the surface and ADR, NVP-AEW541 loaded inside. Then this system was characterized by Zeta potential, TEM and other methods, and the entrapment efficiency, drug loading rate, drug release rate in different pH environment were detected; Experiment was carried out in two groups, HMSN-COOH@ADR fluorescent NVP and free ADR fluorescent NVP group, gathering of the co-delivery system in cells and nucleus was observed by LSCM at different time points; Cells apoptosis and MTT cell inhibition rate were also detected after 24 hours in each group. Results: Zeta potential showed that the charge of HMSN was about-20 mV before modified carboxyl, and rised to-40 mV after modified carboxyl; The size and shape of HMSN were not changed after loading drugs by TEM; The entrapment efficiency was 45% of ADR and 30% of fluorescent NVP, drug loading rate was 7.5% of ADR and 1.4% of fluorescent NVP; The drugs release rate could be significantly improved as the pH value decreased, so the pH value was used as a "switch" which could effectively reduce extracellular nonspecific drug release. The intracellular quantity of HMSN drug delivery system was increased after one hour, and enhanced gradually with time extension. After the same time, the cell apoptosis rate and MTT inhibition rate of HMSN-COOH@ADR fluorescence NVP group were both higher than that of free ADR fluorescent group (P<0.05), indicated the increased cytotoxicity on cells. Conclusion: This HMSN drug delivery system can enter into cells mainly through nonspecific endocytosis, effectively reverse multidrug resistance of ovarian cancer cell SKOV-3/ADR,thus avoide the identification and efflux effect of P-gp. |
[1] CRAVEIRO V,YANG-HARTWICH Y,HOLMBERG J C,et al.Phenotypic modifications in ovarian cancer stem cells following Paclitaxel treatment[J].Cancer Med,2013,2(6):751-762.
[2] TOMONO T,KAJITA M,YANO K,et al.,Adenovirus vector infection of non-small-cell lung cancer cells is a trigger for multi-drug resistance mediated by P-glycoprotein[J].Biochem Biophys Res Commun,2016,476(4):183-187.
[3] WU Q,YANG Z,NIE Y,et al.,Multi-drug resistance in cancer chemotherapeutics:mechanisms and lab approaches[J]. Cancer Lett,2014,347(2):159-166.
[4] LI W,ZHANG H,ASSARAF Y G,et al.Overcoming ABC transporter-mediated multidrug resistance:molecular mechanisms and novel therapeutic drug strategies[J].Drug Resistance Updates,2016,27:14-29.
[5] JUN Y W,LEE J HCHEON J,Chemical design of nanoparticle probes for high-performance magnetic resonance imaging[J].Angew Chem Int Ed Engl,2008,47(28):5122-5135.
[6] TANG C,RUSSELL P J,MARTINIELLO-WILKS R,et al.,Concise review:Nanoparticles and cellular carriers-allies in cancer imaging and cellular gene therapy?[J].Stem Cells,2010,28(9):1686-1702.
[7] 蔡阳,朱传东,郑勤.金纳米在肿瘤治疗中的应用[J].现代医学,2016,44(6):893-896.
[8] DOUGLAS J B,SILVERMAN D T,POLLAK M N,et al.Serum IGF-I,IGF-II,IGFBP-3,and IGF-I/IGFBP-3 molar ratio and risk of pancreatic cancer in the prostate,lung,colorectal,and ovarian cancer screening trial[J].Cancer Epidemiol Biomarkers Prev,2010,19(9):2298-2306.
[9] JIN M,BUCK EMULVIHILL M J.Modulation of insulin-like growth factor-1 receptor and its signaling network for the treatment of cancer:current status and future perspectives[J].Oncol Rev,2013,7(1):e3.
[10] PANYAM J,LABHASETWAR V.Biodegradable nanoparticles for drug and gene delivery to cells and tissue[J].Advanced Drug Delivery Reviews,2012,64:61-71.
[11] LEE E S,GAO ZBAE Y H.Recent progress in tumor pH targeting nanotechnology[J].J Control Release,2008,132(3):164-170.
[12] HUANG Y,JIANG Y,WANG H,et al.Curb challenges of the "Trojan Horse" approach:smart strategies in achieving effective yet safe cell-penetrating peptide-based drug delivery[J].Adv Drug Deliv Rev,2013,65(10):1299-1315.
[13] VANAMALA J,REDDIVARI L,RADHAKRISHNAN S,et al.Resveratrol suppresses IGF-1 induced human colon cancer cell proliferation and elevates apoptosis via suppression of IGF-1R/Wnt and activation of p53 signaling pathways[J].BMC Cancer,2010,10:238. |