2. Academic Validation
  3. Methacrylated Carrageenan/Gelatin Interpenetrating Network Microspheres Loaded with Targeted Drugs and combined with PD-L1 Inhibitors for Hepatocellular Carcinoma Treatment

Methacrylated Carrageenan/Gelatin Interpenetrating Network Microspheres Loaded with Targeted Drugs and combined with PD-L1 Inhibitors for Hepatocellular Carcinoma Treatment

  • ACS Appl Mater Interfaces. 2025 Jul 30;17(30):42893-42914. doi: 10.1021/acsami.5c12363.
Mingxi Ma 1,  Chao Yu 2 3 4 5,  Hanyuan Liu 6,  Xuepeng Lv 1,  Haidong Zhu 2 3 4 5,  Weiwei Tang 6,  Gaojun Teng 2 3 4 5,  Fei Xiong 1
Affiliations

Affiliations

  • 1 State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Sciences & Medical Engineering, Southeast University, Nanjing 210009, China.
  • 2 Center of Interventional Radiology and Vascular Surgery, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Department of Radiology, Zhongda Hospital, Medical School, Southeast University, 87 Dingjiaqiao Road, Nanjing 210009, China.
  • 3 National Innovation Platform for Integration of Medical Engineering Education (NMEE), Southeast University, Nanjing 210009, China.
  • 4 Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing 210009, China.
  • 5 State Key Laboratory of Digital Medical Engineering, Southeast University, Nanjing 210009, China.
  • 6 Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Hepatobiliary Cancers, Nanjing Medical University, Nanjing 210000, China.
PMID: 40671639 DOI: 10.1021/acsami.5c12363
Abstract

Hepatocellular carcinoma (HCC) is a highly fatal malignant tumor. The clinical outcomes of vascular interventional therapy for HCC based on existing drug-eluting microspheres remain unsatisfactory. This study adopted a unique fabrication method to synthesize methacrylated carrageenan/gelatin hydrogel embolic microspheres (MCGs). The interpenetrating network formed by these two biocompatible and absorbable natural macromolecules endows MCGs with outstanding mechanical properties and vascular conformity. MCGs could be delivered through microcatheters smoothly, and they are provided in various sizes to accommodate different clinical requirements. Their in vivo degradation behavior is controlled and predictable. Due to the strong anionic nature of carrageenan, MCGs can efficiently load and sustainably release Lenvatinib, achieving the precise delivery of this antiangiogenic targeted drug in the tumor region. Animal models reveal that the microspheres block blood vessels effectively and MCGs allow for high-dose Lenvatinib to have prolonged contact with HCC. We also propose an HCC treatment strategy by combining PD-L1 inhibitors with MCGs carrying Lenvatinib. This combination therapy is safe and effective, and the additive and synergistic effects showed impressive antitumor potency and great clinical application potential.

Keywords

combination therapy; embolic microsphere; hepatocellular carcinoma; immune checkpoint inhibitors; molecularly targeted drug.

Figures
Products