Acoustically responsive polydopamine nanodroplets: A novel theranostic agent

Christophoros Mannaris; Chuanxu Yang; Dario Carugo; Joshua Owen; Jeong Yu Lee; Sandra Nwokeoha; Anjali Seth; Boon Mian Teo

doi:10.1016/j.ultsonch.2019.104782

Acoustically responsive polydopamine nanodroplets: A novel theranostic agent

Ultrason Sonochem. 2020 Jan:60:104782. doi: 10.1016/j.ultsonch.2019.104782. Epub 2019 Sep 6.

Authors

Christophoros Mannaris¹, Chuanxu Yang², Dario Carugo³, Joshua Owen⁴, Jeong Yu Lee⁴, Sandra Nwokeoha⁴, Anjali Seth⁴, Boon Mian Teo⁵

Affiliations

¹ Institute of Biomedical Engineering, Old Road Campus Research Building, University of Oxford, Oxford OX3 7DQ, UK. Electronic address: christophoros.mannaris@eng.ox.ac.uk.
² Key Laboratory of Colloid and Interface Chemistry, Ministry of Education, Shandong University, Jinan 250100, China.
³ Institute of Biomedical Engineering, Old Road Campus Research Building, University of Oxford, Oxford OX3 7DQ, UK; Mechatronics and Bioengineering Science Research Groups, Faculty of Engineering and the Environment, University of Southampton, Southampton, UK.
⁴ Institute of Biomedical Engineering, Old Road Campus Research Building, University of Oxford, Oxford OX3 7DQ, UK.
⁵ Institute of Biomedical Engineering, Old Road Campus Research Building, University of Oxford, Oxford OX3 7DQ, UK; Key Laboratory of Colloid and Interface Chemistry, Ministry of Education, Shandong University, Jinan 250100, China; School of Chemistry, Clayton Campus, Monash University Victoria, 3800, Australia. Electronic address: boonmian.teo@monash.edu.

PMID: 31539725
DOI: 10.1016/j.ultsonch.2019.104782

Abstract

Ultrasound-induced cavitation has been used as a tool of enhancing extravasation and tissue penetration of anticancer agents in tumours. Initiating cavitation in tissue however, requires high acoustic intensities that are neither safe nor easy to achieve with current clinical systems. The use of cavitation nuclei can however lower the acoustic intensities required to initiate cavitation and the resulting bio-effects in situ. Microbubbles, solid gas-trapping nanoparticles, and phase shift nanodroplets are some examples in a growing list of proposed cavitation nuclei. Besides the ability to lower the cavitation threshold, stability, long circulation times, biocompatibility and biodegradability, are some of the desirable characteristics that a clinically applicable cavitation agent should possess. In this study, we present a novel formulation of ultrasound-triggered phase transition sub-micrometer sized nanodroplets (~400 nm) stabilised with a biocompatible polymer, polydopamine (PDA). PDA offers some important benefits: (1) facile fabrication, as dopamine monomers are directly polymerised on the nanodroplets, (2) high polymer biocompatibility, and (3) ease of functionalisation with other molecules such as drugs or targeting species. We demonstrate that the acoustic intensities required to initiate inertial cavitation can all be achieved with existing clinical ultrasound systems. Cell viability and haemolysis studies show that nanodroplets are biocompatible. Our results demonstrate the great potential of PDA nanodroplets as an acoustically active nanodevice, which is highly valuable for biomedical applications including drug delivery and treatment monitoring.

Keywords: Acoustic droplet vaporization; Nanodroplets; Polydopamine; Ultrasound.