(86f) Ultrasmall Polymersomes for Improved Selectivity of Photoacoustic Imaging of Cancer Cells

The hallmark of nanoparticle-based drug delivery and imaging is to selectively kill cancer cells in tumors while reducing undesirable toxic side effects. In nanotheranostics, an imaging agent is co-encapsulated with a drug to monitor biodistribution, pharmacokinetics, tumor penetration, and cellular internalization in real time in order to enhance therapeutic efficacy. A major limitation has been that the large nanoparticle sizes on the order of 100 nm greatly inhibit penetration of the tumor extracellular matrix and endocytosis into tumor cells resulting in low selectivity of drug delivery to tumor cells. We present a transformative approach to overcome both the size and cellular delivery limitations for nanotheranostics with the design and synthesis of ultrasmall (30-40 nm) polymersomes with the ability to achieve high loadings of hydrophilic and/or hydrophobic cancer drugs and the FDA approved near infrared (NIR) photoacoustic imaging (PAI) dye, ICG J aggregates (ICGJ). Monoclonal antibodies conjugated to the surface with click chemistry provide selective uptake into breast cancer cells. Upon reaching the more acidic environment in tumors the polymersomes dissociate to release the cargoes. The co-encapsulation of ICGJ imaging dye and chemotherapeutic drugs into ultrasmall pH-sensitive polymersomes provides key requirements for enabling advancements towards the unmet goal of nanotheranostics to reach and selectively treat cancer cells while monitoring drug release kinetics for personalized dosage control.