Ultrasound-sensitive nanoparticle aggregates for targeted drug delivery

Publication date: September 2017
Source:Biomaterials, Volume 139
Author(s): Anne-Laure Papa, Netanel Korin, Mathumai Kanapathipillai, Akiko Mammoto, Tadanori Mammoto, Amanda Jiang, Robert Mannix, Oktay Uzun, Christopher Johnson, Deen Bhatta, Garry Cuneo, Donald E. Ingber
Here we describe injectable, ultrasound (US)-responsive, nanoparticle aggregates (NPAs) that disintegrate into slow-release, nanoscale, drug delivery systems, which can be targeted to selective sites by applying low-energy US locally. We show that, unlike microbubble based drug carriers which may suffer from stability problems, the properties of mechanical activated NPAs, composed of polymer nanoparticles, can be tuned by properly adjusting the polymer molecular weight, the size of the nanoparticle precursors as well as the percentage of excipient utilized to hold the NPA together. We then apply this concept to practice by fabricating NPAs composed of nanoparticles loaded with Doxorubicin (Dox) and tested their ability to treat tumors via ultrasound activation. Mouse studies demonstrated significantly increased efficiency of tumor targeting of the US-activated NPAs compared to PLGA nanoparticle controls (with or without US applied) or intact NPAs. Importantly, when the Dox-loaded NPAs were injected and exposed to US energy locally, this increased ability to concentrate nanoparticles at the tumor site resulted in a significantly greater reduction in tumor volume compared to tumors treated with a 20-fold higher dose of the free drug.

Graphical abstract

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