AI Article Synopsis
- Chemotherapy for glioblastoma (GBM) struggles with the blood-brain barrier and toxicity, so researchers used a specific Plk1 inhibitor, volasertib (Vol), delivered through a specially designed polypeptide carrier called ANG-CPP.
- ANG-CPP-Vol demonstrated superior properties, including small size, stability, and effective drug release, leading to a significant increase in anti-tumor effects compared to free Vol.
- This novel approach not only effectively inhibited GBM growth in models but also showed lower toxicity, suggesting a promising potential for GBM treatment.
Article Abstract
The chemotherapy toward glioblastoma (GBM) is severely challenged by blood-brain barrier and dose-limiting toxicity. Herein, we adopt brain delivery of Plk1 inhibitor volasertib (Vol), which is highly specific and presents low off-target toxicity, as a new means to treat GBM, for which angiopep-2-docked chimaeric polypeptide polymersome (ANG-CPP) was designed and prepared from poly(ethylene glycol)-b-poly(L-tyrosine)-b-poly(L-aspartic acid) for loading Vol to its watery interior via electrostatic interactions. ANG-CPP loaded with 13.9 wt% Vol (ANG-CPP-Vol) exhibited a small size of about 76 nm, superb colloidal stability (against dilution, serum and long-term storage), and enzyme-triggered drug release behavior (about 73% of Vol released within 8 h with proteinase K). In sharp contrast to free Vol, ANG-CPP-Vol induced complete G2/M cell cycle arrest in U-87 MG GBM cells giving 7.8-times better anti-tumor activity, prolonged circulation time and largely increased GBM enrichment. ANG-CPP-Vol effectively suppressed the growth of orthotopic U-87 MG GBM and significantly boosted mice survival rate. Importantly, ANG-CPP-Vol showed further reduced toxicity over free Vol. This great safety and remarkable efficacy of ANG-CPP-Vol renders it a high potential for treating GBM.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.jconrel.2020.10.043 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Characterization of a novel conditional knockout mouse model to assess efficacy of mRNA therapy in the context of severe ornithine transcarbamylase deficiency.
Mol Ther
January 2025
Moderna, Inc., Cambridge, MA, USA 02142. Electronic address:
Ornithine transcarbamylase deficiency (OTCD) is the most common urea cycle disorder, characterized by hyperammonemia and accompanied by a high unmet patient need. mRNA therapies have been shown to be efficacious in hypomorphic Sparse-fur abnormal skin and hair (Spf-ash) mice, a model of late-onset disease. However, studying the efficacy of ornithine transcarbamylase (OTC) mRNA therapy in traditional knockout mice, a model for severe early-onset OTCD, is hampered by the rapid lethality of the model, and poor lipid nanoparticle (LNP) uptake into neonatal mouse liver.
View Article and Find Full Text PDFEfficient Gene Delivery Admitted by small Metabolites Specifically Targeting Astrocytes in the Mouse Brain.
Mol Ther
January 2025
School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China; Chinese Institute for Brain Research, Beijing 102206, China. Electronic address:
The development of efficient and targeted methods for delivering DNA in vivo has long been a major focus of research. In this study, we introduce a gene Delivery approach Admitted by small Metabolites, named gDAM, for the efficient and targeted delivery of naked DNA into astrocytes in the adult brains of mice. gDAM utilizes a straightforward combination of DNA and small metabolites, including glycine, L-proline, L-serine, L-histidine, D-alanine, Gly-Gly, and Gly-Gly-Gly, to achieve astrocyte-specific delivery of naked DNA, resulting in transient and robust gene expression in these cells.
View Article and Find Full Text PDFClinical advances of mRNA vaccines for cancer immunotherapy.
Med
January 2025
Center for Nanomedicine, Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address:
The development of mRNA vaccines represents a significant advancement in cancer treatment, with more than 120 clinical trials to date demonstrating their potential across various malignancies, including lung, breast, prostate, melanoma, and more challenging cancers such as pancreatic and brain tumors. These vaccines work by encoding tumor-specific antigens and immune-stimulating molecules, effectively activating the immune system to target and eliminate cancer cells. Despite these promising advancements, significant challenges remain, particularly in achieving efficient delivery and precise regulation of the immune response.
View Article and Find Full Text PDFPediatric Brain Tumors in Western Kenya: Patient Outcomes and Healthcare Providers' Perspectives.
Pediatr Blood Cancer
January 2025
Academic Model Providing Access to Healthcare (AMPATH), Eldoret, Kenya.
Background: Pediatric brain tumors are understudied compared to other pediatric malignancies in low- and middle-income countries. Care delivery is inherently dependent on collaboration between multiple departments. This study aimed to present baseline data of pediatric neuro-oncology care in Western Kenya and illustrate barriers and facilitators of multidisciplinary care.
View Article and Find Full Text PDFTransferrin-Based Bismuth Nanoparticles for Radiotherapy with Immunomodulation Against Orthotopic Glioma.
Adv Healthc Mater
January 2025
School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, P. R. China.
Modern radiotherapy frequently employs radiosensitizers for radiation dose deposition and triggers an immunomodulatory effect to enhance tumor destruction. However, developing glioma-targeted sensitizers remains challenging due to the blood-brain barrier (BBB) and multicomponent instability. This study aims to green-synthesize transferrin-bismuth nanoparticles (TBNPs) as biosafe radiosensitizers to enhance X-ray absorption by tumors and stimulate the immune response for glioma therapy.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!