Effect of alkyl chain on cellular uptake and antitumor activity of hydroxycamptothecin nanoparticles based on amphiphilic linear molecules.

Drug-loaded nanoparticles utilizing amphiphilic molecules as nanocarriers were developed broadly for nanoscale drug delivery system. Linear amphiphilic molecule (PEGC) based on PEG and alkyl chain was designed and synthesized. To study the influence of alkyl chain on antitumor activity, 10-hydroxycamptothecin (HCPT) was selected as the hydrophobic drug, amphiphilic molecule (PEGC) and hydrophilic PEG (PEG) were applied as nanocarriers to form HCPT-loaded nanoparticles (HCPT/PEGC NPs and HCPT/PEG NPs). These two nanoparticles presented high drug-loading content, stability, but different release manner and antitumor efficacy. The HCPT/PEGC NPs existed slower release manner but higher antitumor activity than HCPT/PEG NPs, IC value was decreased approximately 8.5-fold against 4T1 cells in vitro. Moreover, the antitumor efficacy of HCPT/PEGC NPs on 4T1-bearing mice was promoted significantly, the inhibition rate based on average tumor weight was 1.5-fold higher than HCPT/PEG NPs, besides, HCPT/PEGC NPs exhibited better tumor accumulation than HCPT/PEG NPs. These results suggested alkyl chain affect the antitumor activity significantly due to nanoparticles decorated with alkyl chains existing higher endocytosis efficacy to cells. According to the enhanced antitumor efficacy, it was suggested that HCPT/PEGC NPs showed the potential application for cancer therapy in clinic, and alkyl chains should be considered for designing biomaterials.