A transformable nanoplatform with multiple therapeutic and immunostimulatory properties for treatment of advanced cancers

Xiangdong Xue; Haijing Qu; Ruonan Bo; Dalin Zhang; Zheng Zhu; Bai Xiang; Longmeng Li; Marina Ricci; Chong-Xian Pan; Tzu-Yin Lin; Yuanpei Li

doi:10.1016/j.biomaterials.2023.122145

A transformable nanoplatform with multiple therapeutic and immunostimulatory properties for treatment of advanced cancers

Biomaterials. 2023 Aug:299:122145. doi: 10.1016/j.biomaterials.2023.122145. Epub 2023 May 4.

Authors

Xiangdong Xue¹, Haijing Qu¹, Ruonan Bo², Dalin Zhang³, Zheng Zhu⁴, Bai Xiang⁵, Longmeng Li³, Marina Ricci³, Chong-Xian Pan⁶, Tzu-Yin Lin⁷, Yuanpei Li⁸

Affiliations

¹ School of Pharmacy, National Key Laboratory of Innovative Immunotherapy, Shanghai Jiao Tong University, Shanghai, 200240, China; Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California Davis, Sacramento, CA, 95817, USA.
² Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California Davis, Sacramento, CA, 95817, USA; School of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, China.
³ Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California Davis, Sacramento, CA, 95817, USA.
⁴ Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02132, USA.
⁵ Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California Davis, Sacramento, CA, 95817, USA; Key Laboratory of Hebei Province for Innovative Drug Research and Evaluation, School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang, Hebei, 050017, China.
⁶ Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02132, USA; VA Boston Healthcare System, Boston, MA, 02132, USA.
⁷ Division of Hematology and Oncology, Department of Internal Medicine, School of Medicine, University of California Davis, Sacramento, CA, 95817, USA.
⁸ Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California Davis, Sacramento, CA, 95817, USA. Electronic address: lypli@ucdavis.edu.

PMID: 37172536
DOI: 10.1016/j.biomaterials.2023.122145

Abstract

Cancer is a complex pathological phenomenon that needs to be treated from different aspects. Herein, we developed a size/charge dually transformable nanoplatform (PDR NP) with multiple therapeutic and immunostimulatory properties to effectively treat advanced cancers. The PDR NPs exhibit three different therapeutic modalities (chemotherapy, phototherapy and immunotherapy) that can be used to effectively treat primary and distant tumors, and reduce recurrent tumors; the immunotherapy is simultaneously activated by three major pathways, including toll-like receptor, stimulator of interferon genes and immunogenic cell death, effectively suppresses the tumor development in combination with an immune checkpoint inhibitor. In addition, PDR NPs show size and charge responsive transformability in the tumor microenvironment, which overcomes various biological barriers and efficiently delivers the payloads into tumor cells. Taking these unique characteristics together, PDR NPs effectively ablate primary tumors, activate strong anti-tumor immunity to suppress distant tumors and reduce tumor recurrence in bladder tumor-bearing mice. Our versatile nanoplatform shows great potential for multimodal treatments against metastatic cancers.

Keywords: Chemotherapy; Drug delivery; Immunotherapy; Multimodal therapy; Phototherapy.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line, Tumor
Immunotherapy
Mice
Nanoparticles* / therapeutic use
Neoplasm Recurrence, Local
Neoplasms* / therapy
Phototherapy
Tumor Microenvironment