Citation: Zerong Pei, Suyun Hu, Huimin Wei, Liqin Ding, Jingbo Liu, Fengyun Li, Hongyu Chen. Multifunctional carrier-free nanodrugs for enhanced delivery and efficacy of hydrophobic antitumor drugs[J]. Chinese Chemical Letters, ;2026, 37(1): 110981. doi: 10.1016/j.cclet.2025.110981 shu

Multifunctional carrier-free nanodrugs for enhanced delivery and efficacy of hydrophobic antitumor drugs

Zerong Pei ^{a, c} ,
Suyun Hu ^a ,
Huimin Wei ^a ,
Liqin Ding ^a ,
Jingbo Liu ^d ,
Fengyun Li ^{a, *,} ,
Hongyu Chen ^{b, *,}

a.
School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
b.
Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese People's Liberation Army General Hospital, Beijing 100853, China
c.
Institute of Chinese Medicine Health Industry, China Academy of Chinese Medical Sciences, Nanchang 330000, China
d.
College of Horticulture and Landscape Architecture, Tianjin Agricultural University, Tianjin 300384, China

lifengyun0518@163.com

chenhy0528@163.com

Received Date: 25 October 2024
Revised Date: 18 February 2025
Accepted Date: 19 February 2025
Available Online: 19 February 2025

Figures(5)

Poor solubility often results in low efficacy of antitumor drugs. Nevertheless, limited research has been conducted on the potential decrease in drug efficacy following the self-assembly of hydrophobic pure drugs into nanodrugs, and solutions to this problem are even rarer. Loading water-insoluble antitumor drugs into nanocarriers offers a promising solution. However, intricate carrier preparation, limited drug loading capacity, and carrier-associated safety remain key challenges. In this study, based on the discovery that hydrophobic gambogic acid (GA) self-assembles into nanostructures with diminished antitumor efficacy in aqueous environments, we developed a carrier-free nanodrug system, designated as GA-S-S-AS nanoparticles (NPs), characterized by straightforward preparation, high drug loading, fluorescence imaging, tumor-targeting, and responsive drug release in reducing environments. Specifically, the hydrophobic GA was covalently linked to the hydrophilic aptamer through a disulfide bond and then self-assembled into the nanodrugs. About 92% of drug was encapsulated in self-assembled NPs, demonstrating remarkable stability under physiological conditions and controlled release of GA in the high-glutathione environment characteristic of tumor sites. Furthermore, by utilizing the synergistic interaction between the enhanced permeability and retention (EPR) effect and ligand-receptor active targeting mechanisms, the nanodrugs significantly increased the accumulation of GA at tumor locations. Consequently, the nanodrugs exhibited optimal therapeutic efficacy against the tumor both in vitro and in vivo, significantly inhibiting tumor growth. Furthermore, the nanodrugs demonstrated enhanced biosafety compared to free GA, effectively reducing GA-induced hepatotoxicity. Taken together, these findings underscore the significant potential of this multifunctional carrier-free nanodrugs for the targeted delivery of GA, thereby laying a foundation for future endeavors aimed at developing novel formulations of hydrophobic antitumor drugs.
- Hydrophobic antitumor drugs,
- Carrier-free,
- Nanodrug,
- Self-assembly,
- Aptamer,
- Reducing environment
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