Co-Encapsulation of Indocyanine Green J-Aggregate and Paclitaxel in Biodegradable Polymersomes for Photoacoustic-Guided Chemotherapy

Treatment of solid tumors remains one of the biggest challenges in oncology. Targeted nanotherapeutics could significantly improve treatment efficacy and reduce side effects. However, their efficient implementation requires knowledge of pharmacokinetics (PK) and biodistribution (BD) during therapy administration that would allow dose optimization for personalized treatment. To address this need, we developed a nanotheranostic platform that combines photoacoustic imaging (PAI) with near-infrared contrast agents (i.e., indocyanine green J-aggregates, ICGJ) and anticancer drugs (i.e., paclitaxel, PTX) co-encapsulated in biodegradable and pH-sensitive sub-100 nm polymersomes (PTX-ICGJ-Ps) that are composed of all FDA-approved materials. The thick hydrophobic membrane of ICGJ-Ps not only provides protection of the imaging agent, ICGJ, but also facilitates high loading of PTX (10% w/w), and pH-dependent sustained release of the drug. PTX-ICGJ-Ps targeted to human epidermal growth factor receptors (PTX-ICGJ-Ps-aEGFR) exhibit a prolonged and target-specific cytotoxic effect on triple-negative breast cancer (TNBC) cells after just 30 min of treatment, which is significantly higher than the treatment with the free drug. Furthermore, the interaction of PTX-ICGJ-Ps-aEGFR with TNBC cells can be monitored by PAI with high specificity and sensitivity. These data indicate that PTX-ICGJ-Ps-aEGFR meet many of the key attributes of a clinically translatable platform for development of image-guided, personalized therapy of TNBC and other tumors.