A multifunctional PEG–PLL drug conjugate forming redox-responsive nanoparticles for intracellular drug delivery

Tumor-targeting, redox-responsive and high drug-loaded nanoparticles were synthesized from poly(ethylene glycol)-b-poly(l-lysine) (PEG-PLL) for enhanced cancer therapy. A hydrophobic drug camptothecin (CPT) was anchored to the lysine residual amines in PEG-PLL via disulfide bonds. Folate acid as targeting group was further introduced to the PLL block via long PEG chains. The conjugate self-assembled into nanoparticles of around 100 nm with hydrophobic CPT moieties forming the core and folate acid targeting groups on the shell. The nanoparticles were expected to be stable in the blood circulation but once internalized via folate receptor-mediated endocytosis, disintegrate and release the drug by glutathione in the cytosol. The nanoparticles could be used as a nanocarrier to further encapsulate other drugs such as doxorubicin for combined chemotherapy. The CPT-conjugated nanoparticles had comparable cytotoxicity to free CPT at low doses but higher cytotoxicity than CPT at high doses.