Glycol chitosan-coated gold nanocages targeting a brain tumor with red light emissions.

Nanocages: The Future of Cancer Treatment?

Theo Raines in Health & Wellness June 2025 • 4 min read.

"Explore how glycol chitosan-coated gold nanocages are revolutionizing glioblastoma phototherapy, offering new hope for brain cancer treatment."

Photodynamic therapy (PDT) has emerged as a clinically approved strategy for cancer treatment. However, its effectiveness is often hampered by the limited water solubility of photosensitizers (PS) and their short wavelength absorption, which restricts deep tissue penetration. Overcoming these limitations is crucial for expanding the applications of PDT, particularly in challenging cancers like glioblastoma.

Glioblastoma, an aggressive type of brain tumor, poses significant challenges due to its infiltrative growth and resistance to conventional treatments. Complete surgical removal is difficult, and the prognosis remains poor despite aggressive multimodal therapies. Researchers are constantly exploring new approaches to improve treatment outcomes and extend patient survival.

Recent advancements in nanotechnology offer promising solutions for enhancing PDT. One such advancement involves the use of gold nanocages (AuNCs) to encapsulate and deliver near-infrared (NIR) photosensitizers. These nanocages not only protect the PS from premature release but also improve their biocompatibility and water solubility, paving the way for more effective and targeted cancer therapy.

Glycol Chitosan-Coated Nanocages: A Breakthrough in Glioblastoma Phototherapy

Glycol chitosan-coated gold nanocages targeting a brain tumor with red light emissions.

A groundbreaking study led by Gantumur Battogtokh and colleagues has introduced an innovative approach to glioblastoma phototherapy. Published in Nanomedicine: Nanotechnology, Biology, and Medicine, the research details the development of glycol chitosan-coated gold nanocages designed to encapsulate a near-infrared photosensitizer (SiNC). This novel formulation aims to enhance the delivery and effectiveness of PDT for brain cancer treatment.

The researchers selected SiNC, a near-infrared photosensitizer, for its ability to absorb light at longer wavelengths, allowing for deeper tissue penetration. They encapsulated SiNC within gold nanocages in the presence of a phase-changing material to ensure its stability and prevent premature release. The nanocages were then coated with glycol chitosan (GC) using two different linkers: a cleavable peptide linkage and a stable cysteine linkage.

Enhanced Biocompatibility: Glycol chitosan coating improves the biocompatibility of the nanocages, reducing toxicity and enhancing their ability to interact with biological systems.
Controlled Release: The cleavable peptide linkage allows for the release of SiNC at the tumor site in response to specific enzymes, maximizing its therapeutic effect.
Improved Water Solubility: Encapsulation in gold nanocages enhances the water solubility of the hydrophobic photosensitizer, facilitating its delivery and uptake by cancer cells.
Neutral Surface Charge: The resulting particles exhibit a neutral surface charge, which promotes better dispersion and reduces aggregation in biological environments.

The study's findings highlight the superior performance of the enzyme-cleavable peptide-linked GC formulation (GC-pep@SiNC-AuNC) compared to free NIR-PS and the stable cysteine-linked GC-AuNC (GC-cys@SiNC-AuNC). The GC-pep@SiNC-AuNC formulation demonstrated stronger phototoxicity and tumor suppression efficacy in a glioblastoma model, indicating its potential as a promising agent for brain cancer phototherapy.

Future Directions and Implications

This research underscores the potential of polymer-coated SiNC-AuNCs as a promising agent for brain cancer phototherapy. Further studies are needed to optimize the formulation, investigate its long-term effects, and evaluate its clinical translatability. The development of targeted nanocarriers like these could revolutionize cancer treatment by improving drug delivery, reducing side effects, and enhancing therapeutic outcomes for patients with glioblastoma and other challenging cancers.

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This article is based on research published under:

DOI-LINK: 10.1016/j.nano.2018.10.007, Alternate LINK

Title: Glycol Chitosan-Coated Near-Infrared Photosensitizer-Encapsulated Gold Nanocages For Glioblastoma Phototherapy

Subject: Pharmaceutical Science

Journal: Nanomedicine: Nanotechnology, Biology and Medicine

Publisher: Elsevier BV

Authors: Gantumur Battogtokh, Oyuntuya Gotov, Ji Hee Kang, Eun Ji Hong, Min Suk Shim, Dongyun Shin, Young Tag Ko

Published: 2019-06-01

Everything You Need To Know

What is glioblastoma and why is it so difficult to treat?

Glioblastoma is an aggressive type of brain tumor characterized by its rapid infiltrative growth and resistance to conventional treatments. The challenges in treating glioblastoma stem from its ability to spread throughout the brain, making complete surgical removal nearly impossible. Furthermore, glioblastoma cells often resist standard therapies, contributing to a poor prognosis for patients. The use of therapies like glycol chitosan-coated gold nanocages aims to overcome these challenges by targeting the tumor more effectively and improving treatment outcomes.

How do glycol chitosan-coated gold nanocages work in photodynamic therapy for glioblastoma?

Glycol chitosan-coated gold nanocages enhance photodynamic therapy (PDT) for glioblastoma in several ways. First, the gold nanocages encapsulate a near-infrared photosensitizer (SiNC), protecting it from premature release and improving its water solubility. Second, the glycol chitosan (GC) coating enhances the biocompatibility of the nanocages, reducing toxicity and promoting interaction with biological systems. The GC-pep@SiNC-AuNC formulation, using a cleavable peptide linkage, allows for controlled release of SiNC at the tumor site in response to specific enzymes, maximizing its therapeutic effect. When exposed to light, the photosensitizer generates reactive oxygen species, which kill cancer cells.

What are the benefits of using SiNC within gold nanocages compared to using the photosensitizer alone?

Using SiNC within gold nanocages provides several key advantages over using the photosensitizer alone. The encapsulation of SiNC inside the gold nanocages enhances its water solubility, which is crucial for effective drug delivery and uptake by cancer cells. Gold nanocages protect SiNC from premature release, ensuring that the photosensitizer reaches the tumor site intact. Furthermore, the use of near-infrared light with SiNC allows for deeper tissue penetration, which is essential for treating glioblastoma, a tumor located deep within the brain. The glycol chitosan coating further enhances biocompatibility and controlled release.

How does the choice of linker in the glycol chitosan coating affect the nanocages' performance?

The choice of linker in the glycol chitosan coating significantly impacts the nanocages' performance, particularly in terms of drug release and therapeutic effect. The study compared two types of linkages: a cleavable peptide linkage and a stable cysteine linkage. The cleavable peptide linkage in GC-pep@SiNC-AuNC allows for the controlled release of SiNC at the tumor site, triggered by specific enzymes present in the tumor microenvironment. This targeted release maximizes the therapeutic effect, as the photosensitizer is activated only where it's needed. In contrast, the stable cysteine linkage (GC-cys@SiNC-AuNC) does not offer this controlled release mechanism, resulting in less efficient tumor suppression.

What are the future implications of this research for cancer treatment?

This research on glycol chitosan-coated gold nanocages has significant implications for the future of cancer treatment. The development of targeted nanocarriers, such as GC-pep@SiNC-AuNC, represents a major step toward improving drug delivery, reducing side effects, and enhancing therapeutic outcomes. This approach could revolutionize the treatment of glioblastoma and other challenging cancers by overcoming limitations of traditional therapies, such as poor drug solubility and lack of tissue penetration. Further studies are needed to optimize the formulation, investigate long-term effects, and assess its clinical translatability, paving the way for more effective and personalized cancer treatments.