Your browser doesn't support javascript.
loading
Stepwise Size Shrinkage Cascade-Activated Supramolecular Prodrug Boosts Antitumor Immunity by Eliciting Pyroptosis.
Liang, Meng-Yun; Zhang, Meng-Jie; Qiu, Wei; Xiao, Yao; Ye, Meng-Jie; Xue, Peng; Kang, Yue-Jun; Sun, Zhi-Jun; Xu, Zhigang.
Afiliación
  • Liang MY; State Key Laboratory of Silkworm Genome Biology, School of Materials and Energy and Chongqing Key Laboratory of Soft-Matter Material Chemistry and Function Manufacturing, Southwest University, Chongqing, 400715, P. R. China.
  • Zhang MJ; The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, 430079, P. R. China.
  • Qiu W; State Key Laboratory of Silkworm Genome Biology, School of Materials and Energy and Chongqing Key Laboratory of Soft-Matter Material Chemistry and Function Manufacturing, Southwest University, Chongqing, 400715, P. R. China.
  • Xiao Y; The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, 430079, P. R. China.
  • Ye MJ; State Key Laboratory of Silkworm Genome Biology, School of Materials and Energy and Chongqing Key Laboratory of Soft-Matter Material Chemistry and Function Manufacturing, Southwest University, Chongqing, 400715, P. R. China.
  • Xue P; State Key Laboratory of Silkworm Genome Biology, School of Materials and Energy and Chongqing Key Laboratory of Soft-Matter Material Chemistry and Function Manufacturing, Southwest University, Chongqing, 400715, P. R. China.
  • Kang YJ; State Key Laboratory of Silkworm Genome Biology, School of Materials and Energy and Chongqing Key Laboratory of Soft-Matter Material Chemistry and Function Manufacturing, Southwest University, Chongqing, 400715, P. R. China.
  • Sun ZJ; The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, 430079, P. R. China.
  • Xu Z; State Key Laboratory of Silkworm Genome Biology, School of Materials and Energy and Chongqing Key Laboratory of Soft-Matter Material Chemistry and Function Manufacturing, Southwest University, Chongqing, 400715, P. R. China.
Adv Sci (Weinh) ; 9(26): e2203353, 2022 09.
Article en En | MEDLINE | ID: mdl-35869614
Effective pyroptosis induction is a promising approach to potentiate cancer immunotherapy. However, the actual efficacy of the present pyroptosis inducers can be weakened by successive biological barriers. Here, a cascaded pH-activated supramolecular nanoprodrug (PDNP) with a stepwise size shrinkage property is developed as a pyroptosis inducer to boost antitumor immune response. PDNPs comprise multiple poly(ethylene glycol) (PEG) and doxorubicin (DOX) drug-polymer hybrid repeating blocks conjugated by ultra-pH-sensitive benzoic imine (bzi) and hydrazone (hyd) bonds. The PEG units endow its "stealth" property and ensure sufficient tumor accumulation. A sharp switch in particle size and detachment of PEG shielding can be triggered by the acidic extracellular pH to achieve deep intratumor penetration. Following endocytosis, second-stage size switching can be initiated by more acidic endolysosomes, and PDNPs disassociate into ultrasmall cargo to ensure accurate intracellular delivery. The cascaded pH activation of PDNPs can effectively elicit gasdermin E (GSDME)-mediated pyroptosis to enhance the immunological response. In combination with anti-PD-1 antibody, PDNPs can amplify tumor suppression and extend the survival of mice, which suggests a powerful immune adjuvant and pave the way for high-efficiency immune checkpoint blockade therapy.
Asunto(s)
Palabras clave

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Profármacos / Neoplasias Límite: Animals Idioma: En Revista: Adv Sci (Weinh) Año: 2022 Tipo del documento: Article Pais de publicación: Alemania

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Profármacos / Neoplasias Límite: Animals Idioma: En Revista: Adv Sci (Weinh) Año: 2022 Tipo del documento: Article Pais de publicación: Alemania