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

in Journal of controlled release : official journal of the Controlled Release Society by Jain Koo, Yuseon Shin, Hyewon Jeon, Jaehyun Cheong, Seongmin Cho, Chanho Park, Ee Chan Song, Jacob D Ramsey, Chaemin Lim, Kyung Taek Oh

TLDR

  • Scientists develop a new way to deliver cancer medication directly to the brain using micelles coated with a special peptide, and find it effective in reducing tumor size and increasing survival rates in an animal model of glioblastoma multiforme.
  • This breakthrough could lead to new and more effective treatments for brain cancers.

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.

Overview

  • The main focus of the study is to develop a novel formulation of polymeric micelles encapsulating a quercetin-etoposide combination for treating glioblastoma multiforme (GBM), a devastating primary tumor of the central nervous system, by enhancing direct drug delivery to the brain through intranasal administration.
  • The study aims to investigate the enhancement of the micelle formulation by conjugating it with a novel and highly potent cell-penetrating peptide (CPP) identified using the intra-dermal delivery technology platform developed by REMEDI Co., Ltd., to improve its brain-targeting capability.
  • The primary objective of the study is to evaluate the efficacy and safety of the CPP-modified micelles encapsulating the quercetin-etoposide combination (CM(QE)) through intranasal administration for treating GBM, with a focus on brain-demand and cellular uptake.

Comparative Analysis & Findings

  • The study found that 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 compared to the unmodified micelle formulation.
  • The animal studies showed significant tumor reduction and increased survival rates in animals treated with CM(QE) via intranasal administration, with no significant changes in body weight observed.
  • The findings of the study suggest that intranasal administration of CM(QE) holds promise as a significant advancement in chemotherapy for GBM, improving the efficacy and safety of treatment.

Implications and Future Directions

  • The study's findings have significant implications for the development of novel therapies for GBM, highlighting the potential of CPP-modified micelles for enhancing direct drug delivery to the brain and improving treatment outcomes.
  • Future studies could explore the use of different CPPs or combinations of CPPs to further enhance the brain-targeting ability of the micelles, as well as investigate the potential of CM(QE) for treating other types of brain cancers.
  • The study also highlights the importance of continued investment in basic research and development of new technologies to improve our understanding of the blood-brain barrier and develop novel treatments for brain cancers.
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