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Nanocomplexes of doxorubicin and DNA fragments for efficient and safe cancer chemotherapy

  1. Author:
    Mohammad, Saad N
    Choi, Yeon Su
    Chung, Jee Young
    Cedrone,Edward
    Neun,Barry
    Dobrovolskaia,Marina
    Yang, Xiaojing
    Guo, Wei
    Chew, Yap Ching
    Kim, Juwan
    Baek, Seunggul
    Kim, Ik Soo
    Fruman, David A
    Kwon, Young Jik

  2. Author Address

    Department of Pharmaceutical Sciences, University of California, Irvine, CA 92697, United States., Nanotechnology Characterization Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, United States., Zymo Research Corporation, Irvine, CA 92604, United States., Pharma Research, Co, Ltd., Seongnam-si, Gyeonggi-do, Republic of Korea., Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, United States., Department of Pharmaceutical Sciences, University of California, Irvine, CA 92697, United States; Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, United States; Department of Biomedical Engineering, University of California, Irvine, CA 92697, United States; Department of Chemical and Biomolecular Engineering, University of California, Irvine, CA 92697, United States. Electronic address: kwonyj@uci.edu.,
    1. Year: 2023
    2. Date: Jan
    3. Epub Date: 2022 12 23
  2. Journal: Journal of Controlled Release : official journal of the Controlled Release Society
    1. 354
    2. Pages: 91-108
  4. Type of Article: Article
  1. Abstract:

    Cancer-targeted therapy by a chemotherapeutic agent formulated in a nanoscale platform has been challenged by complex and inefficient manufacturing, low drug loading, difficult characterization, and marginally improved therapeutic efficacy. This study investigated facile-to-produce nanocomplexes of doxorubicin (DOX), a widely used cancer drug, and clinically approved DNA fragments that are extracted from a natural source. DOX was found to self-assemble DNA fragments into relatively monodispersed nanocomplexes with a diameter of ~70 nm at 14.3% (w/w) drug loading by simple and scalable mixing. The resulting DOX/DNA nanocomplexes showed sustained DOX release, unlike overly stable Doxil®, cellular uptake via multiple endocytosis pathways, and high hematological and immunological compatibility. DOX/DNA nanocomplexes eradicated EL4 T lymphoma cells in a time-dependent manner, eventually surpassing free DOX. Extended circulation of DOX/DNA nanocomplexes, while avoiding off-target accumulation in the lung and being cleared from the liver, resulted in rapid accumulation in tumor and lowered cardio toxicity. Finally, tumor growth of EL4-challenged C57BL/6 mice (syngeneic model) and OPM2-challenged NSG mice (human xenograft model) were efficiently inhibited by DOX/DNA nanocomplexes with enhanced overall survival, in comparison with free DOX and Doxil®, especially upon repeated administrations. DOX/DNA nanocomplexes are a promising chemotherapeutics delivery platform for their ease of manufacturing, high biocompatibility, desired drug release and accumulation, efficient tumor eradication with improved safety, and further engineering versatility for extended therapeutic applications. Copyright © 2022. Published by Elsevier B.V.

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External Sources

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  2. DOI: 10.1016/j.jconrel.2022.12.048
  3. PMID: 36572154
  4. PII : S0168-3659(22)00861-6

Library Notes

  1. Fiscal Year: FY2022-2023
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