Reduction-sensitive polypeptide nanogel conjugated BODIPY-Br for NIR imaging-guided chem/photodynamic therapy at low light and drug dose.

A heavy atoms modified reaction-active photosensitizer NHS-BODIPY-Br possessing efficient near infrared (NIR) fluorescence emission and singlet oxygen generation properties has been synthesized, which can be used for synchronous NIR imaging and photodynamic therapy (PDT). A reduction-sensitive PEGylated polypeptide nanogel was prepared by ring-opening polymerization (ROP) of l-cystine-N-carboxy anhydride. Poly (ethylene glycol) methyl ether was used as initiator and hydrophilic segment, the as-prepared nanogel was conjugated with the NHS-BODIPY-Br molecule by chemical linkage, and it can be directly used as a macrophotosentizer for NIR imaging-guided PDT. In addition, the nanogel also showed good encapsulating ability for doxorubicin (DOX). In the presence of glutathione (10 mM), the obtained NIR nanogel showed obvious reduction-induced drug release behavior. In vitro tests on internalization of the NIR nanogel by HepG2 cells indicated its efficiency in detecting cancer cells. Meanwhile, MTT assays performed on HepG2 cells confirmed that the cancer cells growth could be obviously suppressed (almost all cells) when exposed to an extremely low energy light (25 mW/cm2, 10-15 J/cm2) and low dose of DOX (3-5 μg/ml), indicates an efficient NIR image-guided chem/photodynamic therapy.