(818e) Extending Bioavailability of Polymersomes for Enhanced Tumor Detection

Nanoparticles have emerged as a novel tool enabling targeting and imaging of cancer because they can diffuse through the leaky tumor vasculature and accumulate in the extravascular tissue effectively via the enhanced permeation and retention (EPR) effect.  Successful use of nanoparticles in this application greatly relies on a structural stability of nanoparticles in circulation; however, according to previous studies, nanoparticles which are often used for clinical diagnosis and treatments are plagued by their shorter lifetime in circulation. 

To address this problem, we synthesized a poly(N-hydroxyethyl-DL-aspartamide) modified with pedant alkyl chains and methacrylate groups, termed PHEA-g-C₁₈-MA, which can form a polymersome with chemically cross-linked shell via sequential self-assembly and photo-induced cross-linking reaction of the bilayer.  The resulting polymer and its self-assembled morphology of PHEA-g-C₁₈-MA were investigated by nuclear magnetic resonance and tramission electron microscopy.  The resulting PHEA-g-C₁₈-MA polymersomes with hardened shells exhibited the better in vitro stability than a control, the same polymersome without cross-linked shells.  The polymersome was further functionalized to present a capability of imaging target tumor vasculature by labeling the particle with a near-infrared (NIRF) dye.  The polymersome carrying NIRF dye was injected into mice with squamous cell carcinoma tumors through the tail vein, and its bio-distribution was monitored using a whole-body imaging system.  Interestingly, PHEA-g-C₁₈-MA polymersomes with hardened shells displayed superior capabilities to accumulate in tumor sites and show entire tumor tissue, compared to controls including polymersomes with softer shell. 

We propose that this result should clearly address the important role of structural stabilities of nanoparticles on improving their capabilities to target and image cancer tissue.  In addition, this study serves to provide an invaluable biomedical tool that can significant enhance the quality of the cancer diagnosis or treatment.