A photoacoustic approach for monitoring the drug release of pH-sensitive poly(β-amino ester)s

Drug delivery systems are capable of delivering medications to target sites and controlled releasing payloads to circumvent common problems associated with traditional drugs such as low bioavailability and undesired side-effects. Real-time and spatio-temporal monitoring of the drug release kinetics is crucial for evaluating treatment efficacy. The photoacoustic tomography (PAT) imaging technique has become an emerging tool for non-invasively studying the drug release behaviour of drug-loaded nanocarriers under physiological conditions. In this work, we prepared PEG modified poly(beta-amino ester) graft copolymers with pH-sensitive properties, which were proved by pyrene fluorescence and pH titration measurements. The copolymers could form micelle-like nanoparticles with hydrophobic cores at pH 7.4 and dissociated into single chains in mildly acidic media. The anticancer drug doxorubicin (DOX) and the near-infrared fluorescence squaraine (SQ) dye as a built-in PAT reporter molecule were loaded into the hydrophobic core of micelles simultaneously, and their release profiles were investigated by using UV/Vis, fluorescence spectrometers and the PAT technique. The polymer micelles were stable at pH 7.4 and released the loaded molecules quickly under mildly acidic conditions, accompanied by the change of photoacoustic signals. The drug-loaded micelles entered into human breast cancer MCF-7 cells by endocytosis and accumulated in the lysosomes that provide an acidic environment to promote the release of DOX, which were monitored by PAT imaging. The time-dependent photoacoustic signals in tissue-mimic phantoms containing micelle-like nanoparticle treated cells reflected the drug release process in lysosomes, which was further validated by using a cell-based confocal fluorescence microscope.