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Enhancing glioblastoma therapy via intranasal administration of highly potent cell-penetrating peptide decorated nanoparticles

Koo, Jain, Shin, Yuseon, Jeon, Hyewon, Cheong, Jaehyun, Cho, Seongmin, Park, Chanho, Song, Ee Chan, Ramsey, Jacob D., Lim, Chaemin, Oh, Kyung Taek·2025·Journal of Controlled Release
DOI 10.1016/j.jconrel.2024.12.058
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Abstract

Glioblastoma multiforme (GBM) is a devastating primary tumor of the central nervous system with a significantly poor prognosis. The primary challenge in treating GBM lies in the restrictive nature of the blood-brain barrier (BBB), impeding effective drug delivery to the brain. In this study, intranasal polymeric micelles encapsulating a quercetin-etoposide combination were developed to induce synergistic apoptotic effects and enhance direct drug delivery to the brain. However, the in vivo anticancer efficacy of the unmodified micelle formulation via intranasal administration remains limited. Therefore, this aims to investigate the enhancement of the formulation by conjugating the micelles with a novel and highly potent cell-penetrating peptide (CPP), RMMR1, identified using the intra-dermal delivery technology platform developed by REMEDI Co., Ltd. This modification seeks to enhance the brain-targeting capability of the micelles. The CPP-modified micelles encapsulating the quercetin-etoposide combination (CM(QE)) demonstrated superior in vivo brain-delivery efficiency and enhanced cellular uptake after intranasal administration. Furthermore, animal studies showed significant tumor reduction and increased survival rates, with no significant changes in body weight observed. These findings suggest that intranasal administration of CM(QE) holds promise as a significant advancement in chemotherapy for GBM.

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Metadata

Authors
Koo, J., Shin, Y., Jeon, H., Cheong, J., Cho, S., Park, C., Song, E. C., Ramsey, J. D., Lim, C., & Oh, K. T.
Venue
Journal of Controlled Release
Publisher
Elsevier BV
Published
2025-02
Volume
378
Pages
997-1012
ISSN
0168-3659
DOI
10.1016/j.jconrel.2024.12.058
Cited by
23
References
2
Language
en
Licence
Funders
  • CHA University (CHA-202301130001)
  • Korea Ministry of Science and ICT (2021R1A2C2008519, 2022R1C1C2002949, 2022R1A5A6000760)
  • National Research Foundation of Korea
  • Small and Medium Business Administration (S3209979)

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