Multifunctional dextran micelles as drug delivery carriers and magnetic resonance imaging probes

Multifunctional nanoparticles combining diagnostic and therapeutic agents into a single platform make cancer theranostics possible and have attracted wide interests in the field. In this study, a multifunctional nanocomposite based on dextran and superparamagnetic iron oxide nanoparticles(SPIO) was prepared for drug delivery and magnetic resonance imaging(MRI). Amphiphilic dextran was synthesized by grafting stearyl acid onto the carbohydrate backbone, and micelle was formed by the resulted amphiphilic dextran with low critical micelle concentration at 1.8 mg L-1. Doxorubicin(DOX) and a cluster of the manganese-doped iron oxide nanoparticles(Mn-SPIO)nanocrystals were then coencapsulated successfully inside the core of dextran micelles, resulting in nanocomposites with diameter at about 100 nm. Cell culture experiments demonstrated the potential of these Mn-SPIO/DOX nanocomposites as an effective multifunctional nanoplatform for the delivery of anticancer drug DOX with a loading content(DLC) of 16 %. Confocal laser scanning microscopyreveals that the Mn-SPIO/DOX had excellent internalization ability against MCF-7/Adr cells after 2-h labeling compared with free DOXáHCl. Under a 3.0-T MRI scanner, Mn-SPIO/DOX nanocomposite-labeled cells in gelatin phantom show much darker images than the control. Their transverse relaxation(T2) rate is also significantly higher than that of the control cells(33.9 versus 2.3 s-1). Our result offers an effective strategy to treat MCF-7/Adr at optimized low dosages with imaging capability.

Reduction of polyethylenimine-coated iron oxide nanoparticles induced autophagy and cytotoxicity by lactosylation

Superparamagnetic iron oxide(SPIO)nanoparticles are excellent magnetic resonance contrast agents and surface engineering can expand their applications.When covered with amphiphilic alkyl-polyethyleneimine(PEI),the modified SPIO nanoparticles can be used as MRI visible gene/drug delivery carriers and cell tracking probes.However,the positively charged amines of PEI can also cause cytotoxicity and restricts their further applications.In this study,we used lactose to modify amphiphilic low molecular weight polyethylenimine(C_(12-)PEI_(2K))at different lactosylation degree.It was found that the N-alkyl-PEI-lactobionic acid wrapped SPIO nanocomposites show better cell viability without compromising their labelling efficacy as well as MR imaging capability in RAW 264.7 cells,comparing to the unsubstituted ones.Besides,we found the PEI induced cell autophagy can be reduced via lactose modification,indicating the increased cell viability might rely on down-regulating autophagy.Thus,our findings provide a new approach to overcome the toxicity of PEI wrapped SPIO nanocomposites by lactose modification.

Cisplatin and paclitaxel co-delivery nanosystem for ovarian cancer chemotherapy

We have designed and developed an effective drug delivery system using biocompatible polymer of poly(ethylene glycol)-polyaspartic acid(mPEG-PAsp)for co-loading the chemotherapy drugs paclitaxel(PTX)and cisplatin(CP)in one nano-vehicle.This study aimed to improve the anti-cancer effi-cacy of combinations of chemotherapy drugs and reduce their side effects.mPEG-PAsp-(PTX/Pt)nano-micelles disperse well in aqueous solution and have a narrow size distribution(37.863.2 nm)in dynamic light scattering(DLS).Drug release profiles found that CP released at pH 5.5 was signifi-cantly faster than that at pH 7.4.MPEG-PAsp-(PTX/Pt)nano-micelles displayed a significantly higher tumor inhibitory effect than mPEG-PAsp-PTX nano-micelles when the polymer concentrations reached 50 lg/mL.Our data indicated that polymer micelles of mPEG-PAsp loaded with the combined drug exert synergistic anti-tumor efficacy on SKOV3 ovarian cells via different action mechanisms.Results from our studies suggested that mPEG-PAsp-(PTX/Pt)nano-micelles are promising alternatives for carrying and improving the delivery of therapeutic drugs with different water solubilities.