文献类型： 外文期刊

作者： Sun, Yurong ¹ ; Lin, Yinhua ¹ ; Sun, Huaitao ¹ ; Yang, Junfa ⁵ ; Cheng, Hui ¹ ; Yi, Jia ¹ ; Li, Wenqiang ¹ ; Lu, Gen ³ ; Zhao, Cheng ⁴ ; Jiang, Yuge ¹ ; Zhao, Xinyu ¹ ; Li, Qinglin ¹ ; Wang, Meng ¹ ; Chen, Shuo ¹ ; Pan, Fei ² ; Cao, Yu ¹ ;

作者机构： 1.Anhui Univ Chinese Med, Xinan Key Lab Med Educ, Minist Educ, Hefei 230038, Peoples R China

2.Chinese Acad Agr Sci, Inst Apicultural Res, State Key Lab Resource Insects, Beijing 100093, Peoples R China

3.Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Wuhan 430074, Peoples R China

4.Nanjing Drum Tower Hosp Grp, Anqing Petrochem Hosp, Anqing 246003, Peoples R China

5.Anhui Med Univ, Hosp 2, Dept Emergency Surg, Hefei 230601, Peoples R China

6.Anhui Univ Chinese Med, Funct Act & Resource Utilizat Edible & Med Fungi J, Hefei 230038, Peoples R China

关键词： Computational screening; Nano formulation; Bufalin; Cancer therapy

期刊名称：CHEMICAL ENGINEERING JOURNAL （ 影响因子：13.2； 五年影响因子：13.5 ）

ISSN： 1385-8947

年卷期： 2025 年 514 卷

页码：

收录情况： SCI

摘要： The nano-formulation of nature bioactive molecules can effectively address prolonged drug delivery challenges and treat various conditions. However, identifying optimal drug-carrier combinations is resource-intensive, necessitating thorough evaluations of drug-carrier compatibility, biocompatibility, and drug loading capacity. Here, we report a computationally driven virtual screening platform that employs third-generation amphiphilic dendrimers (C18-D3.0 and 2C18-D3.0) as representative delivery vehicles. This platform integrates drug-likeness screening, binding affinity assessment, and computational toxicology to enable rapid, large-scale screening of drug-vector combinational nano-formulations. Utilizing this platform, we identified the therapeutic payload bufalin (a natural steroidal drug molecule) was identified from 695,130 bioactive molecules in the COCONUT database. To evaluate the effectiveness of this computational strategy, we characterized the nanoparticle in terms of anti-tumor efficacy assessment. The results indicated that 2C18-D3.0/Bufalin exhibited significant anti-cancer activity, with an IC50 of 31 nM-merely one twenty-fourth that of free Bufalin. Additionally, tumor volume was approximately 0.18 times that of Bufalin group, with complete disappearance in some tumors (n = 2 out of 6). Notably, 2C18-D3.0/Bufalin enhanced the presence of M1 macrophages and CD8 + T cells within tumor microenvironment, highlighting its immunostimulatory effects. Furtherly, organoid imaging based on clinical tumor samples validated the high anti-cancer activity of 2C18-D3.0/Bufalin and its potential for clinical application. This study elucidated the synergistic relationship between bioactive molecules and carriers, highlighting that optimal therapeutic efficacy required a well-matched carrier to enhance activity, while carriers rely on strongly interacting active molecules to unlock their full potential. In this context, AI techniques facilitated the identification of potential and promising drug-carrier combination formulations during the virtual screening process. We envision that this approach could accelerate the development of safer and more effective nano-formulations for various therapeutics.