pH-Sensitive microgels functionalized with folic acid

One of the most promising strategies in anticancer therapies is the targeted delivery through malignancy-associated cellular markers. The design of new synthetic devices with enhanced stimuli-responsive sensitivity and targeting ligands is a promising field for the development of cancer-specific delivery systems. One of the pathways to achieve this aim is the chemical functionalization of nanodevices such as microgels. The p-nitrophenyl acrylate (NPA) is an active ester molecule with a group that can be easily cleavaged by the nucleophilic attack of species such as amines. This modification consists of an easy chemical reaction that leads to several types of functionalized microgels, which are originally made up of NPA as one of their constituent monomers. Here is reported the chemical functionalization of NPA-based microgels by incorporating pH-sensitive functional groups and folic acid as a tumor targeting ligand into the same initial polymer network. For this purpose, microgels of p-nitrophenyl acrylate (NPA)-co-methacrylamide (MeAM) synthesized by precipitation polymerization, were modified with two different pyridine derivatives: 2-aminomethylpyridine (2-AMP) and 2-aminopyridine (2-AP), thus pH-sensitive microgels with acid pH swelling capacity were obtained. The equilibrium swelling behaviour was studied as a function of pH, ionic strength, copolymer composition and type of pyridine derivative. In addition, the microgels were derivatized with ethylene diamine, to obtain amino-functionalized microgels to which the folic acid was subsequently attached as the targeting ligand. As final step, pH-sensitive groups and folic acid were equimolarly attached to the polymer chains to obtain the fully functionalized microgels. (C) 2008 Elsevier Ltd. All rights reserved.