Chimeric poly(N-isopropylacrylamide)-b-poly(3,4-dihydroxy-L-phenylalanine) nanocarriers for temperature/pH dual-stimuli-responsive theranostic application

Abstract

A series of poly(N-isopropylacrylamide)60-block-poly(3,4-dihydroxy-L-phenylalanine)n (p(NIPAM)60-b-p(DOPA)n) (n = 30, 50, 75, 100) copolymers have been prepared by combining reversible addition fragmentation chain transfer polymerization with ring opening polymerization of N-carboxyanhydride α-amino acid using N-heterocyclic carbene as an organocatalyst. The copolymers form spherical nanoparticles with an average diameter of ~100 nm by self-assembly. Doxorubicin (Dox) is encapsulated in the spherical nanocarriers with a drug loading efficiency of 44.2%. The iron(III) ions are coordinated to the copolymer matrix via catechol moieties in p(DOPA) units, resulting in temperature/pH dual-stimuli-responsive nanocarriers. The microstructures and Dox loading procedure can be predicted using a dissipative particle dynamics simulation. Cellular uptake and theranostic anticancer activity studies reveal that the nanocarriers release encapsulated Dox preferentially in cancer cells in response to morphological changes induced by variations in temperature and pH. Both cell internalization and cytotoxicity in A2780 ovarian cancer cells and in vivo biodistribution studies demonstrate that the Dox-loaded nanocarriers fabricated by p(NIPAM)-b-p(DOPA) copolymers can be a promising candidate for cancer therapy.