2. Academic Validation
  3. Long-lasting postoperative analgesia with local anesthetic-loaded hydrogels prevent tumor recurrence via enhancing CD8+T cell infiltration

Long-lasting postoperative analgesia with local anesthetic-loaded hydrogels prevent tumor recurrence via enhancing CD8+T cell infiltration

  • J Nanobiotechnology. 2023 Feb 10;21(1):50. doi: 10.1186/s12951-023-01803-8.
Mingxu Zhao # 1,  Shasha Zhu # 2,  Ding Zhang # 1 3,  Chang Zhou 1 3,  Zhilai Yang 1,  Chunhui Wang 4,  Xuesheng Liu 5,  Jiqian Zhang 6
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Key Laboratory of Anesthesia and Perioperative Medicine of Anhui Higher Education Institutes, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, 20032, China.
  • 2 Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, 20032, China. zss90328@mail.ustc.edu.cn.
  • 3 Department of Anesthesiology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, 20032, China.
  • 4 Department of Anesthesiology, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, 20032, China. wangchhaymz@163.com.
  • 5 Department of Anesthesiology, Key Laboratory of Anesthesia and Perioperative Medicine of Anhui Higher Education Institutes, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, 20032, China. liuxuesheng@ahmu.edu.cn.
  • 6 Department of Anesthesiology, Key Laboratory of Anesthesia and Perioperative Medicine of Anhui Higher Education Institutes, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, 20032, China. jiqianzh@mail.ustc.edu.cn.
  • # Contributed equally.
PMID: 36765361 DOI: 10.1186/s12951-023-01803-8
Abstract

Postoperative pain (POP) can promote tumor recurrence and reduce the Cancer patient's quality of life. However, POP management has always been separated from tumor treatment in clinical practice, and traditional postoperative analgesia using opioids is still unsatisfactory for patients, which is not conducive to tumor treatment. Here, ropivacaine, a popular amide-type LA, was introduced into a Pluronic F127 hydrogel. Postoperative analgesia with ropivacaine-loaded hydrogels reduced the incidence of high-dose ropivacaine-induced convulsions and prolonged pain relief for more than 16 h. More interestingly, ropivacaine-loaded hydrogel was found to upregulate major histocompatibility complex class I (MHC-I) in tumor cells by impairing Autophagy. Therefore, a hydrogel co-dopped with ropivacaine and TLR7 Agonist imiquimod (PFRM) was rationally synthesized. After postoperative analgesia with PFRM, imiquimod primes tumor-specific CD8+T cells through promoting DCs maturation, and ropivacaine facilitates tumor cells recognition by primed CD8+T cells through upregulating MHC-I. Consequently, postoperative analgesia with PFRM maximumly increases CD8+T cells infiltration into residual tumor tissue and prevents tumor recurrence. Overall, this study for the first time provides an LA-based approach for simultaneous long-lasting postoperative analgesia and prevention of tumor recurrence.

Keywords

Hydrogel; Local anesthetic; MHC-I; Postoperative pain; Tumor recurrence.

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