An Optimally Fabricated Platform Guides Cancer‐Specific Activation of Chemotherapeutic Drugs and Toxicity‐Free Cancer Treatment

• Published in: Advanced healthcare materials 2022-08, Vol.11 (15), p.e2200765-n/a
• Main Authors: Moon, Ok Jeong, Yoon, Chul Joo, Lee, Bo‐Ram, Lee, Jeewon
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoferritin; Biocompatibility; Cancer; cancer chemotherapy; Cancer therapies; cancer‐specific drug activations; cathepsin E; Cell Line, Tumor; Chemotherapy; Deoxyribonucleic acid; DNA; DNA biosynthesis; DNA damage; Doxorubicin; Doxorubicin - pharmacology; Doxorubicin - therapeutic use; Drug Delivery Systems; Drugs; Gemcitabine; human heavy chain ferritin platforms; Mice; Mitomycin C; Neoplasms - drug therapy; Organs; Peptides; Toxicity; toxicity‐free treatments
• ISSN: 2192-2640; 2192-2659
• DOI: 10.1002/adhm.202200765

Cancer chemotherapeutic drugs such as doxorubicin, mitomycin C, and gemcitabine, which are mostly small synthetic molecules, are still clinically useful for cancer treatment. However, despite considerable therapeutic efficacy, severe toxicity‐associated problems, which are mainly caused by the non‐specific mode of action such as chromosomal DNA damage and interference in the DNA replication even in normal cells, remain unresolved and a major challenge for safer and thus more widespread adoption of chemotherapy. Herein, an innovative platform is developed through beneficially integrating core peptide units into highly‐ordered, stable, and flexibly guest‐adaptable structure of apoferritin, which simultaneously fulfills high‐capacity loading of chemotherapeutic drugs compared with the case of FDA‐approved antibody‐drug conjugates, efficient drug targeting to cancer cells, and cancer cell‐specific drug release and activation. This approach dramatically reduces drug toxicity to normal cells, significantly enhances efficacy in in vivo cancer treatment without toxicity to normal organs of mice, and thus is expected to open up a novel clinical route to break through the limits of current cancer chemotherapy. The optimized structures to enable cancer cell‐specific activation of chemotherapeutic drugs are constructed through integrating core peptide units into highly‐ordered, stable, and guest‐adaptable structure of human heavy chain ferritin (huHF) scaffold. After endocytosis to cancer and normal cells, the drugs are released from huHF‐drug conjugates in cancer cells, whereas in normal cells the huHF‐drug conjugates remain inactive without drug release.