Construction and anti-tumor activity of miR-34a and miriplatin co-loaded cationic liposomes
Objective The aim of this study was to develop cationic liposomes capable of co-delivering miR-34a and miriplatin for a synergistic anticancer effect in cancer treatment.Methods Miriplatin loaded cationic liposome(MCL)was prepared using the thin film dispersion method,while the co-incubation method was used to prepare miR-34a and miriplatin co-loaded cationic liposome(MCL/miR-34a).Based on particle size,polydispersion coefficient(PDI),Zeta potential,concentration of miriplatin,liposomal formulationwere optimized,including kinds of helper phospholipids(DOPE,DOPC,DMPC,DSPC,PC-98T),the molar ratio of cationic phospholipid DOTAP to DOPE,the ratio of N/P,the amount of DSPE-mPEG2000 and cholesterol.The antitumor effect of MCL/miR-34a on the proliferation of MDA-MB-231,HepG2,KB and AsPC-1 cells was evaluated using Rhodamine B method.Results Through prescription optimization,MCL/miR-34a was successfully prepared with uniform particle size(200 nm±23 nm),narrow distribution(PDI=0.242±0.01),suitable potential(45 mV±8 mV),and high encapsulation rate(99.2%of miR-34a,99.8%of miriplatin).In comparison to monotherapy with either miR-34a or miriplatin alone,MCL/miR-34a significantly improved the anti-tumor efficacy on four tumor cell lines with a synergistic antitumor effect.Conclusion The findings indicate that MCL/miR-34a can significantly improve the effectiveness of antitumor treatment,and may function as an innovative nano delivery system for co-administration of nucleic acid drugs and chemotherapeutic drugs.
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