Abstract
Conventional cancer chemotherapies often exhibit insufficient therapeutic outcomes and dose-limiting toxicity. Therefore, there is a need for novel therapeutics and formulations with higher efficacy, improved safety, and more favorable toxicological profiles. This has promoted the development of nanomedicines, including systems for drug delivery, but also for imaging and diagnostics. Nanoparticles loaded with drugs can be designed to overcome several biological barriers to improving efficiency and reducing toxicity. In addition, stimuli-responsive nanocarriers are able to release their payload on demand at the tumor tissue site, preventing premature drug loss. This review focuses on ultrasound-triggered drug delivery by nanocarriers as a versatile, cost-efficient, non-invasive technique for improving tissue specificity and tissue penetration, and for achieving high drug concentrations at their intended site of action. It highlights aspects relevant for ultrasound-mediated drug delivery, including ultrasound parameters and resulting biological effects. Then, concepts in ultrasound-mediated drug delivery are introduced and a comprehensive overview of several types of nanoparticles used for this purpose is given. This includes an in-depth compilation of the literature on the various in vivo ultrasound-responsive drug delivery systems. Finally, toxicological and safety considerations regarding ultrasound-mediated drug delivery with nanocarriers are discussed.
Highlights
Cancer is one of the leading causes of death worldwide [1] and, despite the continuous progress in modern medicine, effective tumor diagnosis and treatment remain challenging problems
Strong hyperthermia is applied for the dilatation of blood vessels and a higher permeability of vessel walls induced at mild tumor tissue ablation, using HIFU with a local◦ temperature increase up to 50–80 °C [37]
Gao et al [110] prepared a microbubble-liposome complex carrying two different cytotoxic drugs followed by applying the ultrasound targeted microbubble destruction (UTMD) method, which represents a mode of drug release that relies on mechanical US stimuli
Summary
Cancer is one of the leading causes of death worldwide [1] and, despite the continuous progress in modern medicine, effective tumor diagnosis and treatment remain challenging problems. Pharmaceutics 2021, 13, 1135 the tumor tissue Such modifications can facilitate drug delivery across several biological barriers as well as mediate cell penetration, solubilization, protection from degradation and renal filtration, enhancement of bioavailability, sustained release, immunoevasion (e.g., nanoparticle escape from RES by PEGylation), safe delivery of higher drug doses to tumor cells under avoiding side effects [9], targeting, and triggered activation (controlled release systems) [10,11]. Toxicological aspects (biocompatibility) and safety issues play an important role in this context as well and are major barriers for the translation of this promising technology towards clinical application [13]. They should be already addressed in early stages of SDDS development. The aim of this paper is to highlight successful examples of recent developments in the field of US-triggered drug delivery nanosystems for cancer treatment, including toxicological and safety considerations in this respect
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