TY - JOUR
T1 - An Optimally Fabricated Platform Guides Cancer-Specific Activation of Chemotherapeutic Drugs and Toxicity-Free Cancer Treatment
AU - Moon, Ok Jeong
AU - Yoon, Chul Joo
AU - Lee, Bo Ram
AU - Lee, Jeewon
N1 - Funding Information:
This study was supported by the National Research Foundation of Korea (NRF) grant funded by Korea government (MEST) (Grant No. NRF2019R1A2C3005771). All mice were maintained and handled under the protocol approved by the Korea University Institutional Animal Care and Use Committee (KOREA-2017-0141). All animal procedures were performed in accordance with recommendations for the proper use and care of laboratory animals.
Publisher Copyright:
© 2022 Wiley-VCH GmbH.
PY - 2022/8/3
Y1 - 2022/8/3
N2 - 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.
AB - 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.
KW - cancer chemotherapy
KW - cancer-specific drug activations
KW - cathepsin E
KW - human heavy chain ferritin platforms
KW - toxicity-free treatments
UR - http://www.scopus.com/inward/record.url?scp=85132190138&partnerID=8YFLogxK
U2 - 10.1002/adhm.202200765
DO - 10.1002/adhm.202200765
M3 - Article
C2 - 35670274
AN - SCOPUS:85132190138
SN - 2192-2640
VL - 11
JO - Advanced healthcare materials
JF - Advanced healthcare materials
IS - 15
M1 - 2200765
ER -