Nano-Enhanced Drug Delivery and Therapeutic Ultrasound for Cancer Treatment and Beyond

Abstract

While ultrasound is most widely known for its use in diagnostic imaging, the energy carried by ultrasound waves can be utilized to influence cell function and drug delivery. Consequently, our ability to use ultrasound energy at a given intensity unlocks the opportunity to use the ultrasound for therapeutic applications. Indeed, in the last decade ultrasound-based therapies have emerged with promising treatment modalities for several medical conditions. More recently, ultrasound in combination with nanomedicines, i.e., nanoparticles, has been shown to have substantial potential to enhance the efficacy of many treatments including cancer, Alzheimer disease or osteoarthritis. The concept of ultrasound combined with drug delivery is still in its infancy and more research is needed to unfold the mechanisms and interactions of ultrasound with different nanoparticles types and with various cell types. Here we present the state-of-art in ultrasound and ultrasound-assisted drug delivery with a particular focus on cancer treatments. Notably, this review discusses the application of high intensity focus ultrasound for non-invasive tumor ablation and immunomodulatory effects of ultrasound, as well as the efficacy of nanoparticle-enhanced ultrasound therapies for different medical conditions. Furthermore, this review presents safety considerations related to ultrasound technology and gives recommendations in the context of system design and operation.

Vascular and extracellular matrix remodeling by physical approaches to improve drug delivery at the tumor site

“…This observation underpinned the extension of sonoporation to be applicable as an anti-cancer treatment. The mechanism is not precisely known but it is hypothesised that the oscillations of cavitating microbubbles generate mechanical forces on the vessel wall and a concomitant permeability and molecule transport improvements [135]. When applied in vivo, microbubbles exposed to low-frequency ultrasound have been shown to cause rupture of microvessels accompanied with extravasation of red blood cells [136].…”

Recent Advances in Nanocarrier-Assisted Therapeutics Delivery Systems

“…Such differences raise the concern of potential mechanical induced cell damage [97]. Another limitation is that the ultrasound beam may be attenuated by the hard tissues and certain tissue associated movements [98].…”

Recent Advances in Micro-Electro-Mechanical Devices for Controlled Drug Release Applications

“…The experience gained from the early MEMS applications has tailored their emerging technology for biotechnological developments including water and environmental monitoring, DNA sequencing and drug discovery ( Bashir, 2004 ). Novel drug delivery methods to release a specific dose of a drug with a certain rate, during an adequate period of time in the targeted tissue and facilitating patient self-administration are becoming increasingly necessary ( Orive et al, 2003 ; Geipel et al, 2007 ; Ruggiero et al, 2018 ; Singh et al, 2019 ; Tharkar et al, 2019 ; Chen Y. et al, 2020 ; Deng et al, 2020 ; Hwang et al, 2020 ). In this sense, advanced biomedical technology will comprise implantable MEMS devices of proven biocompatibility ( Voskerician et al, 2003 ), to carefully release drugs into the body from micro-chambers hosted in the device, eliminating the need for injections or needles ( Grayson et al, 2004 ; Vasudev and Bhansali, 2013 ).…”