Nitric oxide-driven nanotherapeutics for cancer treatment

Zhiqiang Zhao; Xinzhu Shan; Hongyuan Zhang; Xianbao Shi; Peiqi Huang; Jin Sun; Zhonggui He; Cong Luo; Shenwu Zhang

doi:10.1016/j.jconrel.2023.08.038

Nitric oxide-driven nanotherapeutics for cancer treatment

J Control Release. 2023 Oct:362:151-169. doi: 10.1016/j.jconrel.2023.08.038. Epub 2023 Aug 31.

Authors

Zhiqiang Zhao¹, Xinzhu Shan², Hongyuan Zhang¹, Xianbao Shi³, Peiqi Huang¹, Jin Sun¹, Zhonggui He¹, Cong Luo¹, Shenwu Zhang⁴

Affiliations

¹ Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
² Department of State Key Laboratory of Natural and Biomimetic Drugs, College of Pharmaceutical Sciences, Peking University, Beijing 100871, PR China.
³ Department of Pharmacy, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
⁴ Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, PR China. Electronic address: zhangshenwu@aliyun.com.

PMID: 37633361
DOI: 10.1016/j.jconrel.2023.08.038

Abstract

Nitric oxide (NO) is a gaseous molecule endowed with diverse biological functions, offering vast potential in the realm of cancer treatment. Considerable efforts have been dedicated to NO-based cancer therapy owing to its good biosafety and high antitumor activity, as well as its efficient synergistic therapy with other antitumor modalities. However, delivering this gaseous molecule effectively into tumor tissues poses a significant challenge. To this end, nano drug delivery systems (nano-DDSs) have emerged as promising platforms for in vivo efficient NO delivery, with remarkable achievements in recent years. This review aims to provide a summary of the emerging NO-driven antitumor nanotherapeutics. Firstly, the antitumor mechanism and related clinical trials of NO therapy are detailed. Secondly, the latest research developments in the stimulation of endogenous NO synthesis are presented, including the regulation of nitric oxide synthases (NOS) and activation of endogenous NO precursors. Moreover, the emerging nanotherapeutics that rely on tumor-specific delivery of NO donors are outlined. Additionally, NO-driven combined nanotherapeutics for multimodal cancer theranostics are discussed. Finally, the future directions, application prospects, and challenges of NO-driven nanotherapeutics in clinical translation are highlighted.

Keywords: Combination nanotherapeutics; Endogenous NO synthesis; NO donor delivery; Nano drug delivery systems; Nitric oxide.

Publication types

Review