Large Language Model-Assisted Genotoxic Metal-Phenolic Nanoplatform for Osteosarcoma Therapy

Qingxin Fan; Yunxiang He; Jialing Liu; Qinling Liu; Yue Wu; Yuxing Chen; Qingyu Dou; Jing Shi; Qingquan Kong; Yunsheng Ou; Junling Guo

doi:10.1002/smll.202403044

Large Language Model-Assisted Genotoxic Metal-Phenolic Nanoplatform for Osteosarcoma Therapy

Small. 2024 Dec 13:e2403044. doi: 10.1002/smll.202403044. Online ahead of print.

Authors

Qingxin Fan^{1

2}, Yunxiang He^{3

4}, Jialing Liu⁵, Qinling Liu⁶, Yue Wu^{3

4}, Yuxing Chen^{1

2}, Qingyu Dou^{7

8}, Jing Shi⁹, Qingquan Kong^{8

9}, Yunsheng Ou^{1

2}, Junling Guo^{3

4

10

11}

Affiliations

¹ Department of Orthopedics Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, 400016, China.
² Orthopaedic Research Laboratory of Chongqing Medical University, Chongqing Medical University, Chongqing, 400016, China.
³ BMI Center for Biomass Materials and Nanointerfaces, College of Biomass Science and Engineering, Sichuan University, Chengdu, Sichuan, 610065, China.
⁴ National Engineering Laboratory for Clean Technology of Leather Manufacture, Ministry of Education Key Laboratory of Leather Chemistry and Engineering, Sichuan University, Chengdu, Sichuan, 610065, China.
⁵ State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, China.
⁶ Tea Refining and Innovation Key Laboratory of Sichuan Province, College of Horticulture, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China.
⁷ National Clinical Research Center for Geriatrics, Center of Gerontology and Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
⁸ Department of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
⁹ Section of Science and Education, Hospital of Chengdu Office of People's Government of Tibetan Autonomous Region (Hospital.C.T.), Chengdu, Sichuan, 610041, China.
¹⁰ State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, Sichuan, 610065, China.
¹¹ Departments of Chemical, Biological Engineering, The University of British Columbia, Vancouver, BC, V6T1Z4, Canada.

PMID: 39670697
DOI: 10.1002/smll.202403044

Abstract

Osteosarcoma, a leading primary bone malignancy in children and adolescents, is associated with a poor prognosis and a low global fertility rate. A large language model-assisted phenolic network (LLMPN) platform is demonstrated that integrates the large language model (LLM) GPT-4 into the design of multifunctional metal-phenolic network materials. Fine-tuned GPT-4 identified gossypol as a phenolic compound with superior efficacy against osteosarcoma after evaluating across a library of 60 polyphenols based on the correlation between experimental anti-osteosarcoma activity and multiplexed chemical properties of polyphenols. Subsequently, gossypol is then self-assembled into Cu²⁺-gossypol nanocomplexes with a hyaluronic acid surface modification (CuGOS NPs). CuGOS NPs has demonstrated the ability to induce genetic alterations and cell death in osteosarcoma cells, offering significant therapeutic benefits for primary osteosarcoma tumors and reducing metastasis without adverse effects on major organs or the genital system. This work presents an LLM-driven approach for engineering metal-organic nanoplatform and broadening applications by harnessing the capabilities of LLMs, thereby improving the feasibility and efficiency of research activities.

Keywords: drug discovery; genetic toxicity; large language model; metal‐phenolic nanoplatform; osteosarcoma.

Abstract

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