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A multistage assembly/disassembly strategy for tumor-targeted CO delivery

CO gas molecule not only could selectively kill cancer cells but also exhibits limited anticancer efficacy because of the lack of active tumor-targeted accumulation capability. In this work, a multistage assembly/disassembly strategy is developed to construct a new intelligent nanomedicine by encaps...

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Detalles Bibliográficos
Autores principales: Meng, Jin, Jin, Zhaokui, Zhao, Penghe, Zhao, Bin, Fan, Mingjian, He, Qianjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228751/
https://www.ncbi.nlm.nih.gov/pubmed/32440551
http://dx.doi.org/10.1126/sciadv.aba1362
Descripción
Sumario:CO gas molecule not only could selectively kill cancer cells but also exhibits limited anticancer efficacy because of the lack of active tumor-targeted accumulation capability. In this work, a multistage assembly/disassembly strategy is developed to construct a new intelligent nanomedicine by encapsulating a mitochondria-targeted and intramitochondrial microenvironment–responsive prodrug (FeCO-TPP) within mesoporous silica nanoparticle that is further coated with hyaluronic acid by step-by-step electrostatic assembly, realizing tumor tissue–cell–mitochondria–targeted multistage delivery and controlled release of CO in a step-by-step disassembly way. Multistage targeted delivery and controlled release of CO involve (i) the passive tumor tissue–targeted nanomedicine delivery, (ii) the active tumor cell–targeted nanomedicine delivery, (iii) the acid-responsive prodrug release, (iv) the mitochondria-targeted prodrug delivery, and (v) the ROS-responsive CO release. The developed nanomedicine has effectively augmented the efficacy and safety of CO therapy of cancer both in vitro and in vivo. The proposed multistage assembly/disassembly strategy opens a new window for targeted CO therapy.