CD44-Mediated Methotrexate Delivery by Hyaluronan-Coated Nanoparticles Composed of a Branched Cell-Penetrating Peptide

Jisang Yoo, N. Sanoj Rejinold, Dae Yong Lee, Ilkoo Noh, Won Gun Koh, Sangyong Jon, Yeu Chun Kim

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


Branched polymers as drug delivery carriers have been widely attempted due to their outstanding drug loading capability and complex stability like branched polyethyleneimine (B-PEI). However, branched polymers without biodegradability may cause toxicity as they can accumulate in the body. Herein, we report branched modified nona-arginine (B-mR9) composed of redox-cleavable disulfide bonds to form stable complexes with methotrexate (MTX) as an anticancer agent, which is further coated with hyaluronic acid (HA). The HA-coated nanoparticles provide targetability for the CD44 cell surface receptor. The B-mR9-MTX/HA can effectively aid in intracellular MTX delivery to CD44 overexpressing cancer cells being degradable by the reducing environments of the cancer cells. The B-mR9-MTX/HA exhibits not only a glutathione-triggered degradability but also an outstanding CD44-mediated MTX delivery efficacy. In addition, its superior tumor inhibition capability was confirmed through an in vivo study. The results suggest that the HA-coated B-mR9 nanoparticle can be used as a drug delivery platform.

Original languageEnglish
Pages (from-to)494-504
Number of pages11
JournalACS Biomaterials Science and Engineering
Issue number1
Publication statusPublished - 2020 Jan 13

Bibliographical note

Funding Information:
J.Y. and N.S.R. contributed equally. The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. This work was supported by grants from the National Research Foundation of Korea (NRF-2019R1A4A1024116, NRF-2019R1A2C2085962, and NRF-2018M3A9E2024583). The authors declare no competing financial interest.

Publisher Copyright:
© 2019 American Chemical Society.

All Science Journal Classification (ASJC) codes

  • Biomaterials
  • Biomedical Engineering


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