Implantable Microneedle-Mediated Eradication of Postoperative Tumor Foci Mitigates Glioblastoma Relapse
Yulin Zhang1,2, Zezheng Fang1, Zejuan Liu3
1Department of Neurosurgery, Qilu Hospital and Institute of Brain and Brain-Inspired Science, Cheeloo College of Medicine, Shandong University, 107 Wenhua Xi Road, Jinan, Shandong, 250012, China.
Abstract:
Glioblastoma multiforme (GBM) remains incurable despite multimodal treatments after surgical debulking. Almost all patients with GBM relapse within a narrow margin (2-3 cm) of the initial resected lesion due to the unreachable residual cancerous cells. Here, a completely biodegradable microneedle for surgical cavity delivery glioblastoma-associated macrophages (GAMs)-activating immune nano-stimulator that mitigates glioblastoma relapse is reported. The residual tumor lesion-directed biocompatible microneedle releases the nano-stimulator and toll-like receptor 9 agonist in a controlled manner until the microneedles completely degrade over 1 week, efferently induce in situ phonotypic shifting of GAMs from anti- to pro-inflammatory and the tumor recurrence is obviously inhibited. The implantable microneedles offer a significant improvement over conventional transdermal ones, as they are 100% degradable, ensuring safe application within surgical cavities. It is also revealed that the T cells are recruited to the tumor niche as the GAMs initiate anti-tumor response and eradicate residual GBM cells. Taken together, this work provides a potential strategy for immunomodulating the postoperative tumor niche to mitigate tumor relapse in GBM patients, which may have broad applications in other malignancies with surgical intervention.
Insights
A biodegradable microneedle delivers immune nano-stimulators to surgical cavities, reprogramming glioblastoma-associated macrophages (GAMs) to fight residual cancer cells and prevent glioblastoma relapse.
Area of Science:
- Biomaterials Science
- Immunotherapy
- Neuro-oncology
Background:
- Glioblastoma multiforme (GBM) is an aggressive brain cancer with high recurrence rates post-surgery.
- Residual GBM cells in surgical cavities contribute significantly to tumor relapse.
- Current treatments struggle to eliminate microscopic residual disease.
Purpose of the Study:
- To develop a biodegradable microneedle system for targeted delivery of immunomodulatory agents into GBM surgical cavities.
- To investigate the efficacy of this system in reprogramming glioblastoma-associated macrophages (GAMs) and inhibiting tumor recurrence.
- To explore the potential of this approach for treating other malignancies.
Main Methods:
- Fabrication of completely biodegradable microneedles for controlled release of nano-stimulators and toll-like receptor 9 agonists.
- Implantation of microneedles into surgical cavities following tumor debulking.
- In situ analysis of GAM phenotype shifting from anti-tumor to pro-tumorigenic.
- Assessment of T cell recruitment and anti-tumor immune response.
- Evaluation of tumor recurrence inhibition in a GBM model.
Main Results:
- The microneedles degraded completely within one week, releasing therapeutic agents in a controlled manner.
- In situ phenotypic shifting of GAMs from immunosuppressive to pro-inflammatory was observed.
- Significant inhibition of GBM tumor recurrence was achieved.
- Recruitment of T cells to the tumor microenvironment was enhanced, contributing to residual cell eradication.
Conclusions:
- Implantable, biodegradable microneedles offer a promising strategy for immunomodulating the postoperative tumor niche in GBM.
- This approach effectively mitigates glioblastoma relapse by reprogramming local immune cells and enhancing anti-tumor immunity.
- The technology holds potential for broader applications in managing residual disease in other cancers.
