Development of pH-sensitive nanogels for cancer treatment using crosslinked poly(aspartic acid-graft-imidazole)-block-poly(ethylene glycol)

Abstract

pH-sensitive nanogels (NGs) based on poly(aspartic acid-graft-imidazole)-poly(ethylene glycol) were developed using linear PEG with different molecular weights (2000 and 4000 Da) as crosslinkers. The pH-sensitive NGs showed reversible size changes during continuously alternating pH changes. The anticancer treatment potential of pH-sensitive NGs was studied using a model drug, irinotecan (IRI). IRI-loaded NGs (ILNs) showed different drug release kinetics in acidic versus neutral pH, in addition to pH-dependent cytotoxicity. Due to its longer crosslinker, ILN 4 (crosslinked with PEG 4000) showed faster IRI release and a greater magnitude of IRI release than ILN 2 (crosslinked with PEG 2000), resulting in greater cytotoxicity against HCT 116 colorectal cancer cells. These pH-sensitive NGs could potentially be used in cancer treatment by mediating the accumulation and release of IRI from ILNs in the acidic tumor environment and by reducing systemic toxicity due to reversible swelling-shrinkage. (c) 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46268.