Drug-loaded titanium dioxide nanoparticle coated with tumor targeting polymer as a sonodynamic chemotherapeutic agent for anti-cancer therapy

Seonil Kim; Sooseok Im; Eun-Yeong Park; Junseok Lee; Chulhong Kim; Tae-Il Kim; Won Jong Kim

doi:10.1016/j.nano.2019.102110

Drug-loaded titanium dioxide nanoparticle coated with tumor targeting polymer as a sonodynamic chemotherapeutic agent for anti-cancer therapy

Nanomedicine. 2020 Feb:24:102110. doi: 10.1016/j.nano.2019.102110. Epub 2019 Oct 27.

Authors

Seonil Kim¹, Sooseok Im², Eun-Yeong Park³, Junseok Lee¹, Chulhong Kim⁴, Tae-Il Kim⁵, Won Jong Kim⁶

Affiliations

¹ Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
² School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
³ Department of Electrical Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
⁴ Departments of Creative IT Engineering and Electrical Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
⁵ Department of Biosystems & Biomaterials Science and Engineering, College of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea. Electronic address: seal1004@snu.ac.kr.
⁶ Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea. Electronic address: wjkim@postech.ac.kr.

PMID: 31666202
DOI: 10.1016/j.nano.2019.102110

Abstract

Sonodynamic therapy utilizes ultrasound (US)-responsive generation of reactive oxygen species (ROS) from sonosensitizer, and it is a powerful strategy for anti-cancer treatment in combination with chemotherapy. Herein, we report a precisely designed sonodynamic chemotherapeutics which exhibits US-responsive drug release via ROS generation from co-loaded sono-sensitizer. Doxorubicin (DOX)-coordinated titanium dioxide nanoparticles (TNPs) were encapsulated with polymeric phenyboronic acid (pPBA) via phenylboronic ester bond between pPBA and DOX. Loaded DOX was readily released under US irradiation due to the ROS-cleavable characteristics of phenylboronic ester bond. The size of nanoparticles was around 200 nm, and DOX was released by ROS generated under US irradiation. Tumor targeting by PBA moiety, intracellular ROS generation, and combined therapeutic effect against tumor cells were confirmed in vitro. Finally, we demonstrated high tumor accumulation and efficient tumor growth inhibition in tumor-bearing mice under US irradiation, which revealed potential as a multi-functional agent for sonodynamic chemotherapy.

Keywords: Phenylboronic ester bond; Self-assembled nanoparticles; Sonodynamic therapy; Tumor targeting drug delivery; Ultrasound-responsive.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Coated Materials, Biocompatible* / chemistry
Coated Materials, Biocompatible* / pharmacology
Doxorubicin* / chemistry
Doxorubicin* / pharmacology
Drug Delivery Systems*
Female
Humans
MCF-7 Cells
Mice
Mice, Inbred BALB C
Mice, Nude
Nanoparticles* / chemistry
Nanoparticles* / therapeutic use
Neoplasms, Experimental* / metabolism
Neoplasms, Experimental* / pathology
Neoplasms, Experimental* / therapy
Titanium* / chemistry
Titanium* / pharmacology
Ultrasonic Therapy*
Xenograft Model Antitumor Assays

Substances

Coated Materials, Biocompatible
titanium dioxide
Doxorubicin
Titanium