Synthesis of multi-functional nanocapsules via interfacial AGET ATRP in miniemulsion for tumor micro-environment responsive drug delivery

Novel multi-functional polymeric hollow nanocapsules (PHN) based on the crosslinked poly(tert-butyl acrylate) (PtBA) shells were synthesized in a miniemulsion interfacial polymerization via activator generated electron transfer atom transfer radical polymerization (AGET ATRP) technique with N,N'-bis(acryloyl) cystamine (BACy) as cross-linking agent, CuBr2 as catalyst, ascorbic acid (VC) as reducing agent and hexadecane as inert solvent. In the AGET ATRP, a folate-conjugated block copolymer, folatepoly(ethylene glycol)-b-poly(tert-butyl acrylate) (FA-PEG-tBA-Br), was used as macroinitiator/stabilizer, and the specific amphiphilic nature of the copolymer led the extending inward of polymer chains.The DLS analysis directly showed the PHN with an average diameter of 150 nm was obtained. After the PtBA shells were transformed into poly(acrylic acid) (PAA) by hydrolysis, doxorubicin (DOX), as a model drug, was loaded efficiently into the hydrolyzed polymeric hollow nanocapsules (HPHN), then the in vitro release of drug was carried out in phosphate buffer solution (PBS, pH 7.4 or 5.0, with or without DTI' or GSH of different concentrations). It showed that the existence of folate group significantly improved pH stimuliresponsive and DOX-loading capacity of the polymeric nanocapsules. An acidic pH (5.0) and presence of GSH would accelerate the DOX release behavior. Thus, these multi-functional polymeric nanocapsules have excellent available properties in the field of targeted and controlled drug delivery for cancer therapy. (C) 2015 Elsevier B.V. All rights reserved.