Tumour physiology presents a formidable barrier to the delivery of current and emerging anticancer therapeutics, by virtue of the elevated intratumoural pressure, sparse vascularity and dense extracellular matrix. Recent clinical studies have demonstrated that ultrasound-mediated mild hyperthermia in combination with thermosensitive liposomal carriers can significantly improve drug delivery to tumours, but this approach is only directly applicable to therapeutic classes suitable for liposomal encapsulation. Seeking to exploit the mechanical effects of ultrasound, it is first demonstrated that the occurrence of cavitation-induced microstreaming in blood vessels enables the transport of nanomedicines to hundreds of microns from the vessel wall, but that this occurs only in the presence of inertial rather than non-inertial cavitation. This observation motivates the need to develop cavitation nuclei which are capable of ‘following’ unmodified therapeutics into tumours, rather than being confined to the vasculature; and the opportunity to modify the property of the nanomedicines themselves in order to maximize their transport through cavitation-induced microstreaming. A new type of cavitation-inducing gas-stabilized solid sub-micron particles has been developed that permits sustained cavitation activity throughout the tumour volume, significantly enhancing delivery and efficacy of last-generation anti-cancer agents. Further modification of these agents by applying a gold coating that increases their density is found to yield further enhancements in tumour penetration and delivery. These observations demand further mechanistic investigation of cavitation-induced microstreaming from a variety of agents including solid gas-stabilising particles, nanodroplets and microbubbles and its impact on the transport of nanoparticles of different density, shape and charge.

Cavitation-enhanced drug delivery: Microscale transport from nanoscale particles

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.