Current neuropharmacology · 2026
Nanomedicine Strategies for Overcoming Temozolomide Resistance in Glioblastoma.
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Lv Yancheng, Sa Jiazu, Wang Ke, Zhou Jie
Аннотация
BACKGROUND: Glioblastoma multiforme (GBM) is among the deadliest of brain tumors. While temozolomide (TMZ) is the standard treatment, tumors quickly develop resistance, leading to patient relapse. The blood-brain barrier (BBB) and complex tumor microenvironments further limit drug efficacy.
METHODS: We reviewed literature from 2015 to 2024 via PubMed and Web of Science, focusing on nanoparticle-based strategies designed to overcome TMZ resistance. We specifically analyzed how these carriers tackle mechanisms like MGMT overexpression and drug efflux.
RESULTS: Emerging nanomedicines-including liposomes, polymeric nanoparticles, and inorganic carriers- show promise in preclinical models. Key advances include co-delivering TMZ with MGMT inhibitors or siRNAs to re-sensitize tumor cells. Stimuli-responsive systems that release drugs only within the tumor acidity or hypoxia also reduce systemic toxicity.
CONCLUSION: While nanotechnology offers tools to bypass biological barriers and reverse resistance, clinical translation remains slow. Future success depends on solving manufacturing scalability, ensuring long-term safety, and navigating regulatory pathways. Integrating these tools with personalized molecular profiling represents the next step in GBM therapy.
METHODS: We reviewed literature from 2015 to 2024 via PubMed and Web of Science, focusing on nanoparticle-based strategies designed to overcome TMZ resistance. We specifically analyzed how these carriers tackle mechanisms like MGMT overexpression and drug efflux.
RESULTS: Emerging nanomedicines-including liposomes, polymeric nanoparticles, and inorganic carriers- show promise in preclinical models. Key advances include co-delivering TMZ with MGMT inhibitors or siRNAs to re-sensitize tumor cells. Stimuli-responsive systems that release drugs only within the tumor acidity or hypoxia also reduce systemic toxicity.
CONCLUSION: While nanotechnology offers tools to bypass biological barriers and reverse resistance, clinical translation remains slow. Future success depends on solving manufacturing scalability, ensuring long-term safety, and navigating regulatory pathways. Integrating these tools with personalized molecular profiling represents the next step in GBM therapy.