Pure photosensitizer-driven nanoassembly with core-matched PEGylation for imaging-guided photodynamic therapy

Pure drug-assembled nanomedicines(PDANs)are currently under intensive investigation as promising nanoplatforms for cancer therapy.However,poor colloidal stability and less tumor-homing ability remain critical unresolved problems that impede their clinical translation.Herein,we report a core-matched nanoassembly of pyropheophorbide a(PPa)for photodynamic therapy(PDT).Pure PPa molecules are found to self-assemble into nanoparticles(NPs),and an amphiphilic PEG polymer(PPaPEG_(2K))is utilized to achieve core-matched PEGylating modification via the p-p stacking effect and hydrophobic interaction between the PPa core and the PPa-PEG_(2K) shell.Compared to PCL-PEG_(2K) with similar molecular weight,PPa-PEG_(2K) significantly increases the stability,prolongs the systemic circulation and improves the tumor-homing ability and ROS generation efficiency of PPa-nanoassembly.As a result,PPa/PPa-PEG_(2K) NPs exert potent antitumor activity in a 4T1 breast tumor-bearing BALB/c mouse xenograft model.Together,such a core-matched nanoassembly of pure photosensitizer provides a new strategy for the development of imaging-guided theragnostic nanomedicines.

Preparation and evaluation of paclitaxel and Brucea javanica oil core-matched nanoemulsions to treat cancer in vitro and in vivo

Objective: Developed the core-matched nanoemulsions(CMNEs) to co-delivery paclitaxel-oleic acid(PTXOA) prodrug and Brucea javanica oil(BJO) for increasing the antitumor effect.Methods: Antitumor effects and mechanism of PTX-OA/BJO CMNEs that the combination therapy which based on core-matched technology(CMT) were evaluated in vitro and in vivo.Results: The PTX-OA/BJO CMNEs were of nanoscale particle size(108.7 ± 2.3) nm and with entrapment efficiency of >95%. The PTX-OA/BJO CMNEs displayed concentration and time-dependent cytotoxicity against HepG-2 cells and increased G2/M phase block. More importantly, a significant reduction of the tumor volume with no obvious toxicity was observed in nude mice model following administration of PTX-OA/BJO CMNEs compared with the control treated with normal saline(P < 0.05), which suggested the excellent efficacy in vivo. It was further found that the enhanced effectiveness of PTX-OA/BJO CMNEs were associated with the ability of inducing apoptosis of the tumor cells, as well as obviously inhibiting tumor cell proliferation and the activity of TOPOⅡ.Conclusion: Co-encapsulation of two drugs with different mechanisms allows simultaneous interruption of diverse anticancer pathways, resulting in increased therapeutic response and lower toxicity.