Facile synthesis of size-tunable stable nanoparticles via click reaction for cancer drug delivery

The stability and size of polymeric nanoparticles are two of the most important parameters determining their pharmacokinetics and tumor/drug accumulation efficiency in cancer-drug delivery. Herein, we report a facile one-pot synthesis of crosslinked nanoparticles (CNPs) with tunable sizes and polyethylene glycol (PEG) shells via click reactions. Simply by adjusting the contents of the macromonomer (PEG monoacrylate) in its reaction with ethylene diacrylate and a crosslinker containing hexa-thiols groups, the sizes of the resulting PEGylated crosslinked nanoparticles could be easily tuned from 10 to 90 nm. These nanoparticle cores could encapsulate hydrophobic drugs such as doxorubicin (DOX), and the unreacted thiol and acrylate groups could be used for drug conjugation or labeling. Thus, the nanoparticles provide a multifunctional platform for drug delivery. In vivo studies showed that the larger nanoparticles (about 83.7 nm) had a much longer blood-circulation time and better tumor-targeting efficiency. One of our most important findings was that the drug encapsulated in the crosslinked nanoparticles, even though little was released at pH 7.4 under in vitro conditions, had much faster blood clearance than the nanoparticles’ carrier, suggesting that drug release in the bloodstream was significant.