2. Academic Validation
  3. Capsaicin-induced Ca2+ overload and ablation of TRPV1-expressing axonal terminals for comfortable tumor immunotherapy

Capsaicin-induced Ca2+ overload and ablation of TRPV1-expressing axonal terminals for comfortable tumor immunotherapy

  • Nanoscale. 2025 Feb 6;17(6):3288-3305. doi: 10.1039/d4nr04454a.
Jian Sun 1 2 3 4,  Deqiang Wang 5,  Yiying Wei 1,  Danyang Wang 1,  Zhengkun Ji 5,  Wanru Sun 1,  Xin Wang 6,  Pingyu Wang 4,  Nicola Paccione Basmadji 7 8,  Eider Larrarte 7,  José Luis Pedraz 8 9 10 11,  Murugan Ramalingam 8 9 10 11 12 13,  Shuyang Xie 3 4,  Ranran Wang 1 2
Affiliations

Affiliations

  • 1 Institute of Rehabilitation Medicine, School of Rehabilitation Medicine, Binzhou Medical University, Yantai 264003, People's Republic of China. wangrr@bzmc.edu.cn.
  • 2 State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing, 100029, People's Republic of China.
  • 3 Shandong Laboratory of Advanced Materials and Green Manufacturing, Yantai 264000, People's Republic of China. shuyangxie@aliyun.com.
  • 4 Key Laboratory of Tumor Molecular Biology, Binzhou Medical University, Yantai 264003, People's Republic of China.
  • 5 Yantai Affiliated Hospital of Binzhou Medical University, Yantai 264003, People's Republic of China.
  • 6 Department of Rehabilitation Medicine, Clinical Medical College, Yangzhou University, Yangzhou 225000, People's Republic of China.
  • 7 TECNALIA, Basque Research & Technology Alliance (BRTA) Miñano, Spain.
  • 8 NanoBioCel Group, Laboratory of Pharmacy and Pharmaceutical Technology. Department of Pharmacy and Food Science, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), 01006 Vitoria-Gasteiz, Spain. rmurug2000@gmail.com.
  • 9 Joint Research Laboratory (JRL) on Bioprinting and Advanced Pharma, Development, A Joint Venture of TECNALIA and University of the Basque Country (UPV/EHU), Centro de investigación Lascaray Ikergunea, Avenida Miguel de Unamuno, 01006 Vitoria-Gasteiz, Spain.
  • 10 Bioaraba Health Research Institute, Jose Atxotegi, s/n, 01009 Vitoria-Gasteiz, Spain.
  • 11 Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Institute of Health Carlos III, 28029 Madrid, Spain.
  • 12 IKERBASQUE, Basque Foundation for Science, 48013 Bilbao, Spain.
  • 13 School of Basic Medical Sciences, Binzhou Medical University, Yantai 264003, People's Republic of China.
PMID: 39688368 DOI: 10.1039/d4nr04454a
Abstract

As a common malignancy symptom, Cancer pain significantly affects patients' quality of life. Approximately 60%-90% of patients with advanced Cancer experience debilitating pain. Therefore, a comprehensive treatment system that combines Cancer pain suppression and tumor treatment could provide significant benefits for these patients. Here, we designed a manganese oxide (MnO2)/Bovine serum albumin (BSA)/polydopamine (PDA) composite nanoplatform internally loaded with capsaicin for Cancer pain suppression and immunotherapy. MBD&C nanoparticles (NPs) can ablate tumor-innervated sensory nerve fibers via Transient receptor potential vanilloid 1 (TRPV1) channels, thereby reducing the pain caused by various inflammatory mediators. The ablation of TRPV1+ nerve terminals can also decrease the secretion of Calcitonin gene-related peptide (CGRP) and substance P (SP) in sensory nerve fibers, thus reducing the tumor pain and inhibit tumor progression. MBD&C can promote calcium influx by activating overexpressed TRPV1 channels on the tumor membrane surface, thereby achieving Cancer Immunotherapy induced by endogenous CA2+ overloading. In addition, MnO2 NPs can alleviate tumor hypoxia and mitigate the immunosuppressive tumor microenvironment (TME). Ultimately, this treatment system with dual capabilities of inhibiting tumor growth and relieving Cancer pain makes comfortable tumor therapy feasible and paves the way for the development of patient-centered approaches to Cancer treatment in the future.

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