2. Academic Validation
  3. Hypoxia-responsive Azocalixarene-doxycycline host-guest complex for synergistic myopia control

Hypoxia-responsive Azocalixarene-doxycycline host-guest complex for synergistic myopia control

  • J Control Release. 2025 Dec 29:390:114586. doi: 10.1016/j.jconrel.2025.114586.
Shan He 1,  Pei-Juan Wu 1,  Li Zhang 1,  Jia-Xue Wu 1,  Hou-Li Li 1,  Kun Yi 1,  Qiu-Yun Sun 1,  Zi-Yang Wang 2,  Yu-Xin Yue 2,  Dong-Sheng Guo 2,  Ke Hu 1,  Xiao-Bei Huang 3,  Wen-Juan Wan 4
Affiliations

Affiliations

  • 1 The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Prevention and Treatment on Major Blinding Diseases, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing 400010, China.
  • 2 College of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Key Laboratory of Functional Polymer Materials (Ministry of Education), Frontiers Science Center for New Organic Matter, Collaborative Innovation Center of Chemical Science and Engineering, Nankai University, Tianjin 300071, China.
  • 3 Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing 400714, China. Electronic address: [email protected].
  • 4 The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Prevention and Treatment on Major Blinding Diseases, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing 400010, China. Electronic address: [email protected].
PMID: 41475499 DOI: 10.1016/j.jconrel.2025.114586
Abstract

Myopia is one of the most common visual impairments worldwide. Recent studies suggest that scleral hypoxia may act as an early trigger for myopia, initiating oxidative stress (OS) that disrupts extracellular matrix (ECM) remodeling and, in turn, drives axial elongation. In this study, we constructed a novel hypoxia-responsive host-guest complex, DOX@SAC4A, by encapsulating doxycycline (DOX) within sulfonated azocalix[4]arene (SAC4A). In vitro, this system significantly reduced DOX cytotoxicity and enabled efficient hypoxia-triggered drug release. Moreover, the intrinsic activity of SAC4A synergistically enhanced the antioxidant and anti-apoptotic effects of DOX, helping to maintain ECM homeostasis. In vivo studies further confirmed that DOX@SAC4A selectively targeted hypoxic sclera and markedly increased local drug accumulation. Consequently, it effectively suppressed myopia progression in guinea pigs by delaying axial elongation and alleviating myopic refractive shift. In conclusion, DOX@SAC4A is a multifunctional drug delivery system that offers both therapeutic effects and targeted delivery, with promising potential for myopia prevention and control.

Keywords

Combinational therapy; Doxycycline; ECM remodeling; Host-guest interaction; Myopia.

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