Redox and pH Responsive Nano-Vesicles of PEGylated Hyperbranched Poly(amidoamine)-Doxorubicin Conjugate for the Improvement of Cancer Therapy

摘要

In this work, redox and pH responsive vesicles of PEGylated hyperbranched poly(amidoamine)-doxorubicin (PPCD) conjugates were prepared for the improvement of cancer therapy. The PPCD 3/1 and PPCD 6/1 conjugates were respectively prepared by the acid sensitive cis-aconityl linkage between doxorubicin and differently PEGylated hPAMAM (PEG3-g-hPAMAM and PEG(6)-g-hPAMAM). The PPCD vesicles were prepared by disulfide-crosslinking the micelles formed in THF and then transferring them from THF into water. The crosslinked PPCD vesicle with a higher PEGylated degree showed a measurable decrease in size and zeta potential. Both the crosslinked PPCD vesicles could be disassembled into small-sized conjugates under the redox condition. The drug release profiles showed that the both vesicles presented stimuli-triggered drug release in acidic and reducing environment and lower DOX leakage under neutral condition. The cytotoxicity assay reflected that both the PPCD vesicles could effectively kill the gastric cancer MGC803 cells, and PPCD 6/1 vesicle with smaller size presented higher cytotoxicity than PPCD 3/1 vesicle. Considering the more applicable size (about 100 nm), higher capacity of killing tumor cells and better compatibility, the PPCD-6 vesicle with higher PEGylation degree is more favorable to promote the therapeutic effect of cancer, and will be more suitable as drug delivery system for solid tumor treatment.