Affordable Access

deepdyve-link
Publisher Website

NIR-responsive polydopamine-based calcium carbonate hybrid nanoparticles delivering artesunate for cancer chemo-photothermal therapy.

Authors
  • Zhong, Wenzhao1
  • Wong, Ka Hong1
  • Xu, Fujian2
  • Zhao, Nana2
  • Chen, Meiwan3
  • 1 State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR, China. , (China)
  • 2 Key Laboratory of Biomedical Materials of Natural Macromolecules, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, China. , (China)
  • 3 State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR, China. Electronic address: [email protected] , (China)
Type
Published Article
Journal
Acta biomaterialia
Publication Date
Apr 02, 2022
Identifiers
DOI: 10.1016/j.actbio.2022.03.051
PMID: 35381398
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Artesunate (AS), the first-line treatment of malaria with a satisfactory safety profile, has been repurposed as a potential anticancer candidate as it mainly generates reactive oxygen species (ROS) through its intrinsic endoperoxide bridge reacting with ferrous-based catalysts to suppress cancer cell growth. However, further clinical translation of AS is hindered by the attenuated anticancer efficacy due to insufficient ROS generation. Herein, we rationally integrated hydrophobic-modified AS (hAS) with biomimetic polydopamine (PDA) and biomineral calcium carbonate to fabricate high AS-loaded nanomedicine (Ca-PDA/[email protected]) for cancer chemo-photothermal therapy, which exerted anticancer effects in the following ways: (1) the heat was generated when PDA was irradiated by near-infrared (NIR) light for photothermal therapy. Meanwhile, the increased temperature accelerated the production of ROS from hAS, thus enhancing the anticancer efficacy of hAS-based chemotherapy; (2) hAS-mediated chemotherapy boosted the cancer inhibition effect of photothermal therapy by arousing the intracellular ROS levels in the presence of endogenous ferrous ions and sensitizing cancer cells to thermal ablation; (3) the integration of calcium carbonate into the nanoparticle facilitated the pH-responsive drug release for precise treatment. Such hybrid nanoparticles exhibited a combinational antitumor effect of photothermal therapy and chemotherapy in vivo with no systemic toxicity. Taken together, our work presents a facile strategy to improve the anticancer efficacy of AS by combining chemical modification and photothermal therapy-assisted endoperoxide bridge cleavage, which may offer opportunities to pave the way for clinical translation of AS-based nanomedicines. STATEMENT OF SIGNIFICANCE: The clinical translation of artesunate (AS) is hindered by the attenuated anticancer efficacy due to insufficient ROS generation. Herein, we rationally integrated hydrophobic-modified AS (hAS) with biomimetic polydopamine (PDA) and biomineral calcium carbonate to fabricate high AS-loaded nanomedicine (Ca-PDA/[email protected]) for improved cancer chemo-photothermal therapy. The heat generated from PDA in response to near-infrared light irradiation could locally ablate tumor as well as accelerate the production of ROS by hAS, thus enhancing the anticancer efficacy of hAS-based chemotherapy. On the other hand, hAS-based chemotherapy amplified the intracellular oxidative stress, sensitizing cancer cells to thermal ablation. Our work presents a facile strategy to improve the anticancer efficacy of AS by combining chemical modification and photothermal therapy-assisted endoperoxide bridge cleavage. Copyright © 2022. Published by Elsevier Ltd.

Report this publication

Statistics

Seen <100 times