A two-photon fluorophore labeled multi-functional drug carrier for targeting cancer therapy, inflammation restraint and AIE active bioimaging

Abstract

Functional drug carriers with simultaneous effective delivery of therapeutic agents to target sites and great imaging ability have attracted great attention in nanomedicine research. In this work, we developed a multi-functional polymeric micelle based on a folate (FA)-modified triblock copolymer P(TPF-co-Ibup)–PAEMA–PPEG@FA as a smart drug delivery system with anti-tumor and anti-inflammatory abilities, charge conversion and FA-mediated enhanced cellular uptake, and AIE active two-photon bioimaging. Anticancer drug curcumin (CUR) was encapsulated with a high loading capacity and these CUR-loaded micelles exhibited great stability with a negatively charged surface in a physiological environment. However, the acidic tumor environment would rapidly trigger charge conversion as well as the reassembly of the micelle. Moreover, the disulfide linkages would be cleaved by GSH in the tumor cell cytoplasm, leading to rapid release of ibuprofen (Ibup) and further triggered CUR release. In vitro and in vivo anticancer studies on 4T1 cells and the anti-inflammatory experiment on RAW 264.7 cells demonstrated that this functional system possessed great dual-therapeutic ability. In addition, with the aid of the two-photon cell and deep tissue imaging of these AIE micelles, the in vitro and in vivo distribution of nanocarriers could be observed. Given the efficient dual therapy for tumor and inflammation and the two-photon cell and deep tissue imaging, these multi-functional micelles showed great potential for simultaneous cancer therapy, inflammation restraint and AIE active two-photon bioimaging.