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Engineered protein cages with enhanced extracellular drug release for elevated antitumor efficacy.
Yan, Wen; Li, Hanlin; Ning, Jiamin; Huang, Shuhao; Jiang, Longguang; Xu, Peng; Huang, Mingdong; Yuan, Cai.
Afiliación
  • Yan W; College of Biological Science and Engineering, Fuzhou University, Fuzhou, Fujian 350108, China.
  • Li H; College of Chemistry, Fuzhou University, Fujian 350108, China.
  • Ning J; College of Biological Science and Engineering, Fuzhou University, Fuzhou, Fujian 350108, China.
  • Huang S; College of Biological Science and Engineering, Fuzhou University, Fuzhou, Fujian 350108, China.
  • Jiang L; College of Chemistry, Fuzhou University, Fujian 350108, China.
  • Xu P; College of Biological Science and Engineering, Fuzhou University, Fuzhou, Fujian 350108, China.
  • Huang M; College of Chemistry, Fuzhou University, Fujian 350108, China. Electronic address: HMD_lab@fzu.edu.cn.
  • Yuan C; College of Biological Science and Engineering, Fuzhou University, Fuzhou, Fujian 350108, China. Electronic address: cyuan@fzu.edu.cn.
Int J Biol Macromol ; 267(Pt 1): 131492, 2024 May.
Article en En | MEDLINE | ID: mdl-38604418
ABSTRACT
Human heavy chain ferritin (HFn) protein cage has been explored as a nanocarrier for targeted anticancer drug delivery. Here, we introduced a matrix metalloproteinases (MMPs)-cleavable sequence into the DE loop of HFn, creating an MMP-responsive variant, MR-HFn, for localized and extracellular drug release. The crystal structure of MR-HFn revealed that the addition of the MMPs recognition sequence did not affect the self-assembly of HFn but presented a surface-exposed loop susceptible to MMPs cleavage. Biochemical analysis indicated that this engineered protein cage is responsive to MMPs, enabling the targeted release of encapsulated drugs. To evaluate the therapeutic potential of this engineered protein cage, monosubstituted ß-carboxy phthalocyanine zinc (CPZ), a type of photosensitizer, was loaded inside this protein cage. The prepared CPZ@MR-HFn showed higher uptake and stronger phototoxicity in MMPs overexpressed tumor cells, as well as enhanced penetration into multicellular tumor spheroids compared with its counterpart CPZ@HFn in vitro. In vivo, CPZ@MR-HFn displayed a higher tumor inhibitory rate than CPZ@HFn under illumination. These results indicated that MR-HFn is a promising nanocarrier for anticancer drug delivery and the MMP-responsive strategy here can also be adapted for other stimuli.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ingeniería de Proteínas / Metaloproteinasas de la Matriz / Liberación de Fármacos / Antineoplásicos Límite: Animals / Humans Idioma: En Revista: Int J Biol Macromol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ingeniería de Proteínas / Metaloproteinasas de la Matriz / Liberación de Fármacos / Antineoplásicos Límite: Animals / Humans Idioma: En Revista: Int J Biol Macromol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos