2. Academic Validation
  3. Enhancing glioblastoma therapy via intranasal administration of highly potent cell-penetrating peptide decorated nanoparticles

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

  • J Control Release. 2025 Feb 10:378:997-1012. doi: 10.1016/j.jconrel.2024.12.058.
Jain Koo 1,  Yuseon Shin 1,  Hyewon Jeon 1,  Jaehyun Cheong 1,  Seongmin Cho 2,  Chanho Park 2,  Ee Chan Song 2,  Jacob D Ramsey 3,  Chaemin Lim 4,  Kyung Taek Oh 5
Affiliations

Affiliations

  • 1 Department of Global Innovative Drugs, The Graduate School of Chung-Ang University, 221 Heukseok-dong, Dongjak-gu, Seoul 06974, Republic of Korea; College of Pharmacy, Chung-Ang University, 221 Heukseok-dong, Dongjak-gu, Seoul 06974, Republic of Korea.
  • 2 Remedi Co., Ltd. Research center, Songdo 21990, Republic of Korea.
  • 3 Center for Nanotechnology in Drug Delivery and Division of Pharmacoengineering and Molecular Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, NC 27599, USA.
  • 4 College of Pharmacy, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si, 13488, Gyeonggi-do, Republic of Korea; CHA Advanced Research Institute, CHA Bundang Medical Center, 335 Pangyo-ro, Bundang-gu, Seongnam-si, 13488 Gyeonggi-do, Republic of Korea. Electronic address: chaemin@cha.ac.kr.
  • 5 Department of Global Innovative Drugs, The Graduate School of Chung-Ang University, 221 Heukseok-dong, Dongjak-gu, Seoul 06974, Republic of Korea; College of Pharmacy, Chung-Ang University, 221 Heukseok-dong, Dongjak-gu, Seoul 06974, Republic of Korea. Electronic address: kyungoh@cau.ac.kr.
PMID: 39724950 DOI: 10.1016/j.jconrel.2024.12.058
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.

Keywords

Cell-penetrating peptide; Combination therapy; Glioblastoma; Intranasal administration; Polymeric micelle.

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