Self-Assembled Pectin-Conjugated Eight-Arm Polyethylene Glycol-Dihydroartemisinin Nanoparticles for Anticancer Combination Therapy

摘要

Most individual anticancer drugs have poor water-solubilities and difficulties in controlling drug release, which significantly limit their clinical applications for cancer treatment. In order to solve these problems, this study reports a novel synthesis method for encapsulating hydroxycamptothecin (HCPT) into pectin-(eight-arm polyethylene glycol)-dihydroartemisinin nanoparticle (PPD) conjugates to form self-assembled PPDH nanoparticles (PPDH NPs). The prepared PPDH NPs contained hydrophilic carriers of pectin and eight-arm polyethylene glycol and the hydrophobic anticancer drugs of dihydroartemisinin and hydroxycamptothecin, for stabilizing particle size, improving water solubility, and achieving drug controlled release. The results indicated that the obtained nanoparticles possessed appropriate size (similar to 84 nm), drug-loaded efficiency (similar to 9.13 wt % DHA), encapsulation efficiency (similar to 12.03 wt % HCPT), and good stability and were pH-dependent. The time-dependent cytotoxicity tests of the PPDH NPs showed that only 4% 4T1 cell and 2% MCF-1 cell survived after 72 h. The PPDH NPs exhibited a higher cytotoxicity, longer blood retention time of free drug (8.0-fold DHA, 7.4-fold HCPT), and more effective cellular uptake. 4T1 tumor-bearing mice treated with the nanoparticles also showed a considerable survival advantage (90.6%) in comparison to those with the free DHA (15.5%) as well as the free HCPT (14.1%). Moreover, it is clearly an elaborate certification that PPDH NPs could reduce the risk of hypersensitivity reactions substantially. Therefore, PPDH NPs have a promising potential for anticancer combination therapy.