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Targeting the undruggable in glioblastoma using nano-based intracellular drug delivery
Sakine Shirvalilou1,2, Samideh Khoei1,2, Reza Afzalipour3,4
1Finetech in Medicine Research Center, Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Abstract:
Glioblastoma (GBM) is a highly prevalent and aggressive brain tumor in adults with limited treatment response, leading to a 5-year survival rate of less than 5%. Standard therapies, including surgery, radiation, and chemotherapy, often fall short due to the tumor's location, hypoxic conditions, and the challenge of complete removal. Moreover, brain metastases from cancers such as breast and melanoma carry similarly poor prognoses. Recent advancements in nanomedicine offer promising solutions for targeted GBM therapies, with nanoparticles (NPs) capable of delivering chemotherapy drugs or radiation sensitizers across the blood-brain barrier (BBB) to specific tumor sites. Leveraging the enhanced permeability and retention effect, NPs can preferentially accumulate in tumor tissues, where compromised BBB regions enhance delivery efficiency. By modifying NP characteristics such as size, shape, and surface charge, researchers have improved circulation times and cellular uptake, enhancing therapeutic efficacy. Recent studies show that combining photothermal therapy with magnetic hyperthermia using AuNPs and magnetic NPs induces ROS-dependent apoptosis and immunogenic cell death providing dual-targeted, immune-activating approaches. This review discusses the latest NP-based drug delivery strategies, including gene therapy, receptor-mediated transport, and multi-modal approaches like photothermal-magnetic hyperthermia combinations, all aimed at optimizing therapeutic outcomes for GBM.
Insights
Nanoparticles offer new hope for treating aggressive glioblastoma (GBM) by delivering drugs across the blood-brain barrier. Advanced nanoparticle strategies, including combined therapies, aim to improve treatment effectiveness and patient survival rates for brain tumors.
Area of Science:
- Nanomedicine
- Oncology
- Biotechnology
Background:
- Glioblastoma (GBM) is an aggressive brain tumor with poor prognosis and limited treatment options.
- Standard therapies face challenges due to tumor location, hypoxia, and incomplete removal.
- Brain metastases also present significant therapeutic challenges.
Purpose of the Study:
- To review recent advancements in nanoparticle (NP)-based drug delivery for glioblastoma.
- To explore NP strategies for overcoming the blood-brain barrier (BBB) and enhancing targeted delivery.
- To discuss novel therapeutic approaches, including combination therapies and immune-activating strategies.
Main Methods:
- Utilizing nanoparticles (NPs) for targeted delivery of chemotherapy drugs and radiation sensitizers.
- Leveraging the enhanced permeability and retention (EPR) effect for preferential NP accumulation in tumors.
- Modifying NP characteristics (size, shape, surface charge) to improve circulation and cellular uptake.
- Investigating multi-modal therapies like photothermal and magnetic hyperthermia using gold nanoparticles (AuNPs) and magnetic NPs.
Main Results:
- NPs demonstrate potential for crossing the BBB and accumulating in GBM tissues.
- Optimized NP properties enhance drug delivery, circulation time, and therapeutic efficacy.
- Combined photothermal and magnetic hyperthermia induces apoptosis and immunogenic cell death.
- Dual-targeted, immune-activating approaches show promise for GBM treatment.
Conclusions:
- Nanomedicine offers promising avenues for targeted glioblastoma therapy.
- NP-based strategies, including gene therapy and multi-modal treatments, can optimize therapeutic outcomes.
- Further research into NP delivery systems is crucial for improving survival rates in GBM patients.
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