Peptide/Doxorubicin Co-Assembled Hydrogel for Hemostatic Control and Sustained Local Chemotherapy after Tumor Surgery

Mol Pharm. 2026 Feb 2;23(2):916-931. doi: 10.1021/acs.molpharmaceut.5c01326. Epub 2026 Jan 19.

Abstract

Effective management of solid tumors requires both surgical resection and sustained local chemotherapy. However, immediate postoperative drug delivery remains challenging due to bleeding risk and the delay in systemic therapy. Here, we report a coassembled peptide/doxorubicin hydrogel (BDO) designed to address this clinical gap by integrating intraoperative hemostasis with localized chemotherapy. The hydrogel is formed via coassembly of a functional peptide (B-cL1), which combines VEGFR inhibition and nanofiber-forming capacity, with doxorubicin. During surgery, the hydrogel rapidly adheres to the tissue interface and promotes hemostasis while enabling sustained drug release at the tumor resection site. Structural characterization and molecular simulations confirm a stable fibrous network facilitated by hydrogen bonding and hydrophobic interactions. In vitro and in vivo studies demonstrate excellent biointerface compatibility, enhanced coagulation, and localized antitumor activity with minimal systemic toxicity. These findings highlight a promising biointerface-engineered strategy for simultaneous bleeding control and site-specific chemotherapeutic delivery during tumor surgery.

Keywords: antitumor; co-assembly; hemostasis; localized drug delivery; peptide hydrogel.

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / administration & dosage
  • Cell Line, Tumor
  • Doxorubicin* / administration & dosage
  • Doxorubicin* / chemistry
  • Drug Delivery Systems / methods
  • Drug Liberation
  • Female
  • Hemostasis / drug effects
  • Hemostatics* / chemistry
  • Humans
  • Hydrogels* / chemistry
  • Mice
  • Neoplasms* / drug therapy
  • Neoplasms* / surgery
  • Peptides* / chemistry

Substances

  • Doxorubicin
  • Peptides
  • Hydrogels
  • Hemostatics
  • Antibiotics, Antineoplastic