Caiying Zhu,Jingjing Xiao,Ming Tang,Hua Feng,Wulian Chen,Ming Du
The preparation of polymer therapeutics capable of controlled release of multiple chemotherapeutic drugs has remained a tough problem in synergistic combination cancer therapy. Herein, a novel dual-drug co-delivery system carrying doxorubicin (DOX) and platinum(IV) (Pt[IV]) was developed. An amphiphilic diblock copolymer, PCL-b-P(OEGMA-co-AzPMA), was synthesized and used as a nanoscale drug carrier in which DOX and Pt(IV) could be packaged together. The copolymers were shell cross-linked by Pt(IV) prodrug via a click reaction. Studies on the in vitro drug release and cellular uptake of the dual-drug co-delivery system showed that the micelles were effectively taken up by the cells and simultaneously released drugs in the cells. Futhermore, the co-delivery polymer nanoparticles caused much higher cell death in HeLa and A357 tumor cells than either the free drugs or single-drug-loaded micelles at the same dosage, exhibiting a synergistic combination of DOX and Pt(IV). The results obtained with the shell cross-linked micelles based on an anticancer drug used as a cross-linking linkage suggested a promising application of the micelles for multidrug delivery in combination cancer therapy.
In this paper, a novel grafted polymer (folate and carboxymethyl-β-cyclodextrin grafted trimethyl chitosan, FCT) was synthesized. Then the FCT nanoparticles (FCT NPs) were fabricated by ionic gelation and the potential of NPs as co-carrier of doxorubicin and siRNA was evaluated. The physicochemical properties of grafted polymer and NPs were characterized and analyzed by fourier transforms infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential and polydispersity index (PDI). The results showed the diameter of NPs ranged from 190 to 240 nm with polydispersity index of 0.192 and zeta potential of +21mv. The prepared NPs exhibited satisfactory drug loading capacity and encapsulation efficiency to doxorubicin and siRNA-survivin. Meanwhile, the prepared NPs could effectively protect siRNA-survivin from degradation of serum RNAase for a long time. Both drugs encapsulated in NPs all exhibited pH-dependent controlled sustained release characteristics and the cytotoxicity study testified that drug drug-loaded FCT NPs significantly improved the efficacy of antitumor drugs . The novel graft polymer was expected to become the co-carrier of anticancer and gene drugs in future with broad application prospects.
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