Efficient intracellular delivery of p53 protein by engineered protein crystals restores tumor suppressing function in vivo
| Autor: | Zaofeng Yang, Michael K. Chan, Marianne M. Lee |
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| Rok vydání: | 2021 |
| Předmět: |
0303 health sciences
Chemistry Endosome Effector Biophysics Bioengineering Translation (biology) Endosomes 02 engineering and technology 021001 nanoscience & nanotechnology In vitro Cell biology Biomaterials 03 medical and health sciences Drug development Mechanics of Materials In vivo Neoplasms Cancer cell Ceramics and Composites Humans Tumor Suppressor Protein p53 0210 nano-technology Protein crystallization 030304 developmental biology |
| Zdroj: | Biomaterials. 271:120759 |
| ISSN: | 0142-9612 |
| Popis: | Direct delivery of proteins into cells holds significant potential for basic research and drug development. However, the poor endosomal escape of conventional delivery strategies remains a challenge, thus limiting the clinical translation of many protein therapeutics. Herein, we report that engineered Cry3Aa protein (Pos3Aa) crystals formed naturally within Bacillus thuringiensis can serve as a vehicle for efficient cytosolic delivery of bioactive proteins. We showed that Pos3Aa-mediated delivery of tumor suppressor p53 protein, a promising therapeutic candidate found to be inactivated in nearly half of human cancers, resulted in the restoration of p53 function in p53-deficient cancer cells, and thereby sensitized them to 5-fluorouracil chemotherapy as demonstrated in in vitro and in vivo models. Our results validate that Pos3Aa crystals can be a robust and effective platform for the cytosolic delivery of effector proteins, and suggest that efficient uptake and endosomal escape could be critical for efficacious p53 protein-based cancer therapy. |
| Databáze: | OpenAIRE |
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