pH-triggered small molecule theranostic nanodrug mediates selective tumor CT imaging and chemotherapy

Xinyang Chen; Longshun Yang; Min Zhang; Ying Zhang; Ruiting Pan; Yan He; Xin Wang; Yangyang Li; Beilei Gong; Rupei Tang; Guoqing Yan

doi:10.1016/j.colsurfb.2025.114896

pH-triggered small molecule theranostic nanodrug mediates selective tumor CT imaging and chemotherapy

Colloids Surf B Biointerfaces. 2025 Jun 20:255:114896. doi: 10.1016/j.colsurfb.2025.114896. Online ahead of print.

Authors

Xinyang Chen¹, Longshun Yang¹, Min Zhang¹, Ying Zhang¹, Ruiting Pan¹, Yan He¹, Xin Wang¹, Yangyang Li², Beilei Gong³, Rupei Tang⁴, Guoqing Yan⁵

Affiliations

¹ Engineering Research Center for Biomedical Materials, Anhui Key Laboratory of Modern Biomanufacturing, School of Life Sciences, Anhui University, 111 Jiulong Road, Hefei, Anhui 230601, China.
² Department of General Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China.
³ Anhui Province Key Laboratory of Clinical and Preclinical Research in Respiratory Disease, Bengbu Medical University, 2600 Donghai Avenue, Bengbu, Anhui 233030, China. Electronic address: huihuang889@sina.com.
⁴ Engineering Research Center for Biomedical Materials, Anhui Key Laboratory of Modern Biomanufacturing, School of Life Sciences, Anhui University, 111 Jiulong Road, Hefei, Anhui 230601, China. Electronic address: tangrp99@iccas.ac.cn.
⁵ Engineering Research Center for Biomedical Materials, Anhui Key Laboratory of Modern Biomanufacturing, School of Life Sciences, Anhui University, 111 Jiulong Road, Hefei, Anhui 230601, China. Electronic address: 17017@ahu.edu.cn.

PMID: 40544686
DOI: 10.1016/j.colsurfb.2025.114896

Abstract

Theranostic nanomedicines have garnered significant attention in cancer management. However, they have yet to achieve clinical transformation due to a lack of precise structure and tumor selectivity. Herein, this work highlights the successful development of a pH-triggered dynamic small molecule nanodrug for targeted tumor theranostics, constructed through self-assembly of orthoester-linked 2,3,5-iodobenzoic acid dimers and doxorubicin by the O/W emulsion solvent evaporation method. The nanodrug exhibits favorable characteristics such as simple preparation, well-defined structure, and high drug loading capacity. Furthermore, it demonstrates superior dynamic alterations in physicochemical properties such as small-to-large size transition, progressive amino protonation and selective drug release across physiological pH (7.4) to tumoral extracellular pH (6.5) and intracellular pH (5.0) levels. These features result in long-term storage stability and circulation longevity while enhancing tumor accumulation by intravenous administration for targeted CT imaging along with significant inhibition of tumor growth. Thus, the pH-triggered small molecule dynamic theranostic nanodrug mediates selective tumor CT imaging and chemotherapy, significantly advancing its potential for clinical application.

Keywords: Dynamic transition; Ortho ester; Small molecule nanodrug; Tumor theranostics.