Multifunctional PEG-PLL Drug Conjugate Forming Responsive Nanoparticles for Intracellular Drug Delivery

poly(ethylene glycol)-b-Poly(L-lysine) was conjugated with different amounts of camptothecin (CPT) via disulfide bonds to form CPT-content controlled glutathione-cleavable micelles in aqueous solution. The micelles were further cross-linked and functionalized with folic acid for enhanced stability in blood circulation and cancer cell-targeting. The multifunctional micelles could enter cancer cells easily through their folate receptor. The cross-links and the disulfide bonds attaching CPT could be cleaved by the high content of glutathione in the cytosol. CPT conjugated nanoparticles had comparable cytotoxicity at low doses to free CPT and higher cytotoxicity at high doses than free CPT, suggesting that the nanoparticles may have potential for improved drug delivery efficacy.