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Phase-changing Nanodroplets as Nanotheranostic Platform for Combination Cancer Therapy

Abstract

Enabling a noninvasive visualization of delivered active pharmaceutical ingredients, nanotheranostics offer the opportunity of rapid optimization of drug delivery systems during in vivo testing. This insight into the kinetics and the fate of nanoparticle-encapsulated therapeutics can aid validate basic properties of the systems without needing to wait a long time for a pathological outcome. In the clinic, this feature would allow for tweaks in the treatment and fast response in modifying a treatment course.

This work describes a versatile nanotheranostic platform capable of providing simultaneous triggered release of active pharmaceutical ingredients (APIs) and ultrasound imaging capabilities, while minimizing off-target effects. The particles described herein consist of a shell-core structure, with a perfluorocarbon core that can be externally vaporized by acoustical or optical stimuli. The activation generates highly echogenic microbubbles, together with the release of the loaded APIs. Notably, the release of APIs in vitro is correlated to the ultrasound signal magnitude after activation, enabling the basis for ultrasound dose-monitoring.

Several applications of the platform are investigated in this context: co-delivery of hydrophobic and hydrophilic chemotherapeutics, delivery of therapeutically relevant large molecules (such as antibodies), as well as multimodal imaging capabilities (fluorescence enhancement) and complex, multiplexed formulations. The main two models being studied are head and neck cancer and triple negative breast cancers. Based on the preliminary results included herein, these loaded nanoparticles look promising for in-vivo ultrasound dose-monitoring of solid tumors. The proposed work aims to optimize the formulations of the nanodroplets for each specific application and test their capabilities in an in vivo context.

Thesis Committee

• Geoffrey Luke, PhD
• Kimberley Samkoe, PhD
• Jack P. Hoopes, PhD
• Emily Day, PhD (external, University of Delaware)

Contact

For more information, contact Theresa Fuller at theresa.d.fuller@dartmouth.edu.