Perylene-Tagged Polycaprolactone Block Copolymers and Their Enzyme-Biodegradable Fluorescent Nanoassemblies for Intracellular Bio-imaging in Cancer Cells

Abstract

The present investigation reports enzyme-biodegradable perylenebisimide (PBI)-tagged polycaprolactone (PCL) block copolymers, and their aqueous nanoassemblies were employed as probes for intracellular bio-imaging in cancer cells. Bishydroxyl functionalized PBI initiator was tailor-made, and it was employed as initiator for the ring opening polymerization (ROP) methodology to make PBI-tagged tert-butyl ester-substituted polycaprolactone (PBI-BPCLx) block copolymers. The deprotection of these copolymers yielded carboxylic acid-substituted PBI-CPCLx amphiphilic block copolymers. The carboxylic blocks were self-assembled to produce stable red-fluorescent nanoparticles of <150 nm in size in aqueous medium with fluorescent quantum yield of ϕ = 0.25–0.30 suitable for bio-imaging application. In vitro studies confirmed that the aliphatic polyester backbone in the PBI-CPCLx polymer nanoparticles was readily biodegradable by lysosomal enzymes under physiological conditions. Dynamic light scattering, gel permeation chromatography, photophysical studies, and MALDI-TOF-MS analysis provided evidence of the enzymatic biodegradation. Cytotoxicity studies revealed that the PBI-CPCLx nanoparticles were highly biocompatible toward both cervical cancer and breast cancer cell lines up to a concentration of 100 μg/mL. Confocal microscopy analysis confirmed the uptake and accumulation of red-fluorescent PBI-CPCLx polymer nanoparticles in the perinuclear environment of the cells. The present approach puts forward a PBI-PCL block copolymer design as enzyme-responsive red-fluorescent nanoprobes for bio-imaging in cancer and normal cells.