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Injectable Nanocomposite Hydrogels Improve Intraperitoneal Co-delivery of Chemotherapeutics and Immune Checkpoint Inhibitors for Enhanced Peritoneal Metastasis Therapy.
Liang, Shu; Xiao, Lingyun; Chen, Tian; Roa, Paola; Cocco, Emiliano; Peng, Zhangwen; Yu, Liu; Wu, Meiying; Liu, Jie; Zhao, Xizhe; Deng, Wenbin; Wang, Xiongjun; Zhao, Chao; Deng, Yang; Mai, Yang.
Afiliación
  • Liang S; School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen 518000, China.
  • Xiao L; School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen 518000, China.
  • Chen T; Precise Genome Engineering Center, School of Life Sciences, Guangzhou University, Guangzhou 510006, China.
  • Roa P; Center Lab of Longhua Branch and Department of Infectious Disease, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, Southern University of Science and Technology), Shenzhen 518020, China.
  • Cocco E; School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen 518000, China.
  • Peng Z; Department of Biochemistry and Molecular Biology/Sylvester Comprehensive Cancer Center, University of Miami/Miller School of Medicine, Miami, Florida 33136, United States.
  • Yu L; Department of Biochemistry and Molecular Biology/Sylvester Comprehensive Cancer Center, University of Miami/Miller School of Medicine, Miami, Florida 33136, United States.
  • Wu M; School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen 518000, China.
  • Liu J; School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen 518000, China.
  • Zhao X; School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen 518000, China.
  • Deng W; ISCTE Business School, BRU-IUL, University Institute of Lisbon, Avenida das Armadas, Lisbon 1649-026, Portugal.
  • Wang X; Department of Chemistry, College of Staten Island, City University of New York, New York, New York 10314, United States.
  • Zhao C; School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen 518000, China.
  • Deng Y; Precise Genome Engineering Center, School of Life Sciences, Guangzhou University, Guangzhou 510006, China.
  • Mai Y; Department of Chemical and Biological Engineering, University of Alabama, Tuscaloosa, Alabama 35487, United States.
ACS Nano ; 18(29): 18963-18979, 2024 Jul 23.
Article en En | MEDLINE | ID: mdl-39004822
ABSTRACT
Intraperitoneal co-delivery of chemotherapeutic drugs (CDs) and immune checkpoint inhibitors (ICIs) brings hope to improve treatment outcomes in patients with peritoneal metastasis from ovarian cancer (OC). However, current intraperitoneal drug delivery systems face issues such as rapid drug clearance from lymphatic drainage, heterogeneous drug distribution, and uncontrolled release of therapeutic agents into the peritoneal cavity. Herein, we developed an injectable nanohydrogel by combining carboxymethyl chitosan (CMCS) with bioadhesive nanoparticles (BNPs) based on polylactic acid-hyperbranched polyglycerol. This system enables the codelivery of CD and ICI into the intraperitoneal space to extend drug retention. The nanohydrogel is formed by cross-linking of aldehyde groups on BNPs with amine groups on CMCS via reversible Schiff base bonds, with CD and ICI loaded separately into BNPs and CMCS network. BNP/CMCS nanohydrogel maintained the activity of the biomolecules and released drugs in a sustained manner over a 7 day period. The adhesive property, through the formation of Schiff bases with peritoneal tissues, confers BNPs with an extended residence time in the peritoneal cavity after being released from the nanohydrogel. In a mouse model, BNP/CMCS nanohydrogel loaded with paclitaxel (PTX) and anti-PD-1 antibodies (αPD-1) significantly suppressed peritoneal metastasis of OC compared to all other tested groups. In addition, no systemic toxicity of nanohydrogel-loaded PTX and αPD-1 was observed during the treatment, which supports potential translational applications of this delivery system.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Neoplasias Peritoneales / Sistemas de Liberación de Medicamentos / Hidrogeles / Quitosano / Nanocompuestos / Inhibidores de Puntos de Control Inmunológico Límite: Animals / Female / Humans Idioma: En Revista: ACS Nano Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Neoplasias Peritoneales / Sistemas de Liberación de Medicamentos / Hidrogeles / Quitosano / Nanocompuestos / Inhibidores de Puntos de Control Inmunológico Límite: Animals / Female / Humans Idioma: En Revista: ACS Nano Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos