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Polyhedral Oligomeric Silsesquioxane-Based Nanoparticles for Efficient Chemotherapy of Glioblastoma
Xiangyang Zhong1, Gang Wei2,3, Boyang Liu1
1Neurosurgery Center, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, 510515, P. R. China.
Abstract:
Glioblastoma (GBM) is the most common lethal brain tumor with dismal treatment outcomes and poor response to chemotherapy. As the regulatory center of cytogenetics and metabolism, most tumor chemotherapeutic molecules exert therapeutic effects in the nucleus. Nanodrugs showing the nuclear aggregation effect are expected to eliminate and fundamentally suppress tumor cells. In this study, a nanodrug delivery system based on polyhedral oligomeric silsesquioxane (POSS) is introduced to deliver drugs into the nuclei of GBM cells, effectively enhancing the therapeutic efficacy of chemotherapy. The nanoparticles are modified with folic acid and iRGD peptides molecules to improve their tumor cell targeting and uptake via receptor-mediated endocytosis. Nuclear aggregation allows for the direct delivery of chemotherapeutic drug temozolomide (TMZ) to the tumor cell nuclei, resulting in more significant DNA damage and inhibition of tumor cell proliferation. Herein, TMZ-loaded POSS nanoparticles can significantly improve the survival of GBM-bearing mice. Therefore, the modified POSS nanoparticles may serve as a promising drug-loaded delivery platform to improve chemotherapy outcomes in GBM patients.
Insights
This study introduces a novel nanodrug delivery system using polyhedral oligomeric silsesquioxane (POSS) nanoparticles to target glioblastoma (GBM) cell nuclei. This approach enhances chemotherapy effectiveness by delivering temozolomide (TMZ) directly to the tumor site, improving survival rates.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Glioblastoma (GBM) is an aggressive brain tumor with limited treatment options.
- Chemotherapeutic drugs often struggle to reach the tumor nucleus effectively.
- Developing targeted drug delivery systems is crucial for improving GBM treatment outcomes.
Purpose of the Study:
- To develop and evaluate a novel nanodrug delivery system for enhanced glioblastoma chemotherapy.
- To investigate the nuclear targeting and therapeutic efficacy of drug-loaded nanoparticles in GBM cells.
- To improve the delivery of temozolomide (TMZ) to glioblastoma nuclei.
Main Methods:
- Fabrication of polyhedral oligomeric silsesquioxane (POSS) nanoparticles.
- Modification of nanoparticles with folic acid and iRGD peptides for targeted delivery.
- Loading of temozolomide (TMZ) into the POSS nanoparticles.
- Evaluation of nanoparticle uptake, nuclear aggregation, and therapeutic effects in GBM cells and GBM-bearing mice.
Main Results:
- Modified POSS nanoparticles effectively targeted and were internalized by GBM cells.
- Nanoparticles demonstrated nuclear aggregation, facilitating direct drug delivery to the nucleus.
- TMZ-loaded POSS nanoparticles induced significant DNA damage and inhibited GBM cell proliferation.
- Treatment with TMZ-loaded POSS nanoparticles significantly improved the survival of GBM-bearing mice.
Conclusions:
- Modified POSS nanoparticles represent a promising platform for targeted glioblastoma chemotherapy.
- Nuclear drug delivery enhances the efficacy of temozolomide against GBM.
- This nanodrug system holds potential for improving clinical outcomes in GBM patients.
