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Updated: Mar 1, 2026
Hyaluronic-Acid Based Hydrogels for 3-Dimensional Culture of Patient-Derived Glioblastoma Cells
Published on: August 24, 2018
Enhanced targeting of invasive glioblastoma cells by peptide-functionalized gold nanorods in hydrogel-based 3D
Diana P N Gonçalves1, Raul D Rodriguez2, Thomas Kurth3
1Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, Hohe Straße 6, 01069 Dresden, Germany.
Abstract:
Cancer stem cells (CSCs) are responsible for drug resistance, tumor recurrence, and metastasis in several cancer types, making their eradication a primary objective in cancer therapy. Glioblastoma Multiforme (GBM) tumors are usually composed of a highly infiltrating CSC subpopulation, which has Nestin as a putative marker. Since the majority of these infiltrating cells are able to elude conventional therapies, we have developed gold nanorods (AuNRs) functionalized with an engineered peptide capable of specific recognition and selective eradication of Nestin positive infiltrating GBM-CSCs. These AuNRs generate heat when irradiated by a near-infrared laser, and cause localized cell damage. Nanoparticle internalization assays performed with GBM-CSCs or Nestin negative cells cultured as two-dimensional (2D) monolayers or embedded in three-dimensional (3D) biodegradable-hydrogels of tunable mechanical properties, revealed that the AuNRs were mainly internalized by GBM-CSCs, and not by Nestin negative cells. The AuNRs were taken up via energy-dependent and caveolae-mediated endocytic mechanisms, and were localized inside endosomes. Photothermal treatments resulted in the selective elimination of GBM-CSCs through cell apoptosis, while Nestin negative cells remained viable. Results also indicated that GBM-CSCs embedded in hydrogels were more resistant to AuNR photothermal treatments than when cultured as 2D monolayers. In summary, the combination of our engineered AuNRs with our tunable hydrogel system has shown the potential to provide an in vitro platform for the evaluation and screening of AuNR-based cancer therapeutics, leading to a substantial advancement in the application of AuNRs for targeted GBM-CSC therapy.
Statement Of Significance:
There is an urgent need for reliable and efficient therapies for the treatment of Glioblastoma Multiforme (GBM), which is currently an untreatable brain tumor form with a very poor patient survival rate. GBM tumors are mostly comprised of cancer stem cells (CSCs), which are responsible for tumor reoccurrence and therapy resistance. We have developed gold nanorods functionalized with an engineered peptide capable of selective recognition and eradication of GBM-CSCs via heat generation by nanorods upon NIR irradiation. An in vitro evaluation of nanorod therapeutic activities was performed in 3D synthetic-biodegradable hydrogel models with distinct biomechanical cues, and compared to 2D cultures. Results indicated that cells cultured in 3D were more resistant to photothermolysis than in 2D systems.
Insights
We developed targeted gold nanorods to eliminate Glioblastoma Multiforme cancer stem cells (CSCs) using near-infrared light. This targeted therapy shows promise for treating this aggressive brain cancer, even within 3D models.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Glioblastoma Multiforme (GBM) is an aggressive brain tumor with poor survival rates, largely due to therapy-resistant cancer stem cells (CSCs).
- CSCs, marked by Nestin, drive tumor recurrence, metastasis, and resistance to conventional treatments.
- There is a critical need for targeted therapies to eradicate CSCs in GBM.
Purpose of the Study:
- To develop and evaluate gold nanorods (AuNRs) functionalized with a peptide for selective targeting and eradication of Nestin-positive GBM CSCs.
- To investigate the efficacy of AuNR-mediated photothermal therapy in 2D and 3D GBM models.
- To assess the role of hydrogel mechanical properties on therapeutic outcomes.
Main Methods:
- Engineered AuNRs functionalized with a peptide for specific GBM-CSC recognition.
- In vitro studies using 2D cell cultures and 3D biodegradable hydrogels containing GBM-CSCs and Nestin-negative cells.
- Near-infrared (NIR) laser irradiation for photothermal therapy.
- Nanoparticle uptake assays and apoptosis analysis.
Main Results:
- AuNRs were selectively internalized by GBM-CSCs via energy-dependent, caveolae-mediated endocytosis.
- Photothermal treatment with AuNRs effectively eliminated GBM-CSCs, inducing apoptosis while sparing Nestin-negative cells.
- GBM-CSCs cultured in 3D hydrogels exhibited increased resistance to photothermal therapy compared to 2D cultures.
Conclusions:
- Engineered AuNRs demonstrate selective targeting and eradication of GBM-CSCs via photothermal therapy.
- The 3D hydrogel system provides a valuable in vitro platform for evaluating cancer therapeutics and understanding drug resistance.
- This approach represents a significant advancement for targeted Glioblastoma Multiforme cancer stem cell therapy.
