Nanoparticles delivering medication to a brain tumor, digital illustration.

Smart Nanoparticles: A New Hope for Beating Brain Tumors?

Soraya Malik in Health & Wellness August 2025 • 4 min read.

"Scientists are exploring how modified natural high-density lipoprotein (HDL) particles can target and deliver drugs to brain tumors more effectively."

Glioblastoma, an aggressive type of brain cancer, poses a significant challenge to modern medicine. Despite advances in surgical techniques, chemotherapy often falls short due to the blood-brain barrier (BBB), which prevents many drugs from reaching the tumor effectively. This barrier, along with the blood-brain tumor barrier (BBTB), necessitates innovative drug delivery systems that can navigate these obstacles and precisely target cancer cells.

Researchers are turning to nanomedicine for solutions. High-density lipoprotein (HDL) particles, known for their role in cholesterol transport, are being explored as potential drug carriers. These nanoparticles can be modified to cross the BBB and BBTB, offering a more direct route to tumor cells. Scientists are investigating dual-modified HDL particles that combine two targeting ligands to enhance their ability to reach and affect glioma cells.

This approach involves modifying natural HDL with specific peptides like T7 and dA7R, which bind to receptors on both the BBB and glioma cells. By combining these modifications, researchers aim to create a drug delivery system that not only penetrates the brain but also specifically targets the tumor, improving treatment outcomes and reducing side effects.

Targeting Tumors with Dual-Modified HDL Particles

Nanoparticles delivering medication to a brain tumor, digital illustration.

The study published in Drug Delivery explores a novel method using dual-modified natural high-density lipoprotein (HDL) particles to deliver drugs directly to glioma cells. The researchers modified HDL with two targeting ligands: T7, a peptide that binds to transferrin receptors (TfR) on the blood-brain barrier (BBB) and glioma cells, and dA7R, a D-peptide ligand that targets vascular endothelial growth factor receptor 2 (VEGFR2), which is overexpressed in tumor angiogenesis. By combining these two ligands, the modified HDL particles can effectively cross the BBB and target glioma cells.

Researchers constructed a drug delivery system based on natural HDL particles, modifying them with T7 and dA7R peptides. These peptides enhance the particles' ability to cross the blood-brain barrier (BBB) and target glioma cells specifically. The drug, 10-hydroxycamptothecin (HCPT), known for its anti-cancer properties, was loaded into these modified HDL particles to test their effectiveness. This dual-targeting approach aims to improve drug delivery and minimize side effects by ensuring the medication reaches its intended target.

The key benefits of using HDL as a drug carrier include:

Natural compatibility and longer circulation in the body.
Small particle size for better diffusion.
Lipid core suitable for carrying hydrophobic drugs.
Potential for dual modification to target specific receptors.

The scientists conducted several experiments to validate the effectiveness of the dual-modified HDL particles. In vitro studies showed that the T7/A7R-HDL particles had a higher affinity for both the BBB and glioma cells compared to single-ligand modified or unmodified HDL. When loaded with HCPT, the T7/A7R-HDL particles demonstrated superior anti-glioma effects in vivo, reducing tumor growth and prolonging survival in mice with intracranial C6 tumors. These results confirm the potential of dual-targeting nanocarriers as a method to improve drug delivery to the brain and enhance glioma treatment.

The Future of Targeted Brain Cancer Therapies

This research highlights the potential of dual-modified HDL particles as a promising strategy for treating glioblastoma. By effectively crossing the BBB and specifically targeting glioma cells, these nanocarriers offer a more precise and efficient method of drug delivery. Further studies are needed to fully understand the mechanisms of targeted delivery and explore the application of T7/A7R-HDL in clinical settings. However, the initial findings suggest a significant step forward in developing more effective and less toxic treatments for brain tumors.

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This article is based on research published under:

DOI-LINK: 10.1080/10717544.2018.1519002, Alternate LINK

Title: Dual-Modified Natural High Density Lipoprotein Particles For Systemic Glioma-Targeting Drug Delivery

Subject: Pharmaceutical Science

Journal: Drug Delivery

Publisher: Informa UK Limited

Authors: Lin Cui, Yuli Wang, Meng Liang, Xiaoyang Chu, Shiyao Fu, Chunsheng Gao, Qianqian Liu, Wei Gong, Meiyan Yang, Zhiping Li, Lian Yu, Chunrong Yang, Zhide Su, Xiangyang Xie, Yang Yang, Chunsheng Gao

Published: 2018-01-01

Everything You Need To Know

Why is glioblastoma so difficult to treat effectively?

Glioblastoma presents treatment challenges due to the blood-brain barrier (BBB) and the blood-brain tumor barrier (BBTB). These barriers prevent many drugs from effectively reaching the tumor. Innovative drug delivery systems, like modified high-density lipoprotein (HDL) particles, are being explored to navigate these obstacles and precisely target cancer cells. This is crucial because standard chemotherapy often falls short in treating glioblastoma due to these protective barriers.

What makes high-density lipoprotein (HDL) particles a promising candidate for drug delivery to brain tumors?

Researchers are exploring high-density lipoprotein (HDL) particles as potential drug carriers because of their natural compatibility, small size, and ability to be modified. By modifying natural HDL with specific peptides like T7 and dA7R, these nanoparticles can cross the BBB and BBTB, offering a direct route to tumor cells. The lipid core of HDL is also suitable for carrying hydrophobic drugs, making them versatile for different types of medications.

How do dual-modified high-density lipoprotein (HDL) particles enhance drug delivery to glioma cells?

Dual-modified high-density lipoprotein (HDL) particles are designed to improve drug delivery by combining two targeting ligands: T7, which binds to transferrin receptors (TfR) on the blood-brain barrier (BBB) and glioma cells, and dA7R, which targets vascular endothelial growth factor receptor 2 (VEGFR2), overexpressed in tumor angiogenesis. This dual-targeting approach allows the modified HDL particles to effectively cross the BBB, target glioma cells specifically, and deliver drugs directly to the tumor site.

What specific experiments were conducted to validate the effectiveness of T7/A7R-HDL particles, and what were the key findings?

The study in Drug Delivery used dual-modified natural high-density lipoprotein (HDL) particles to deliver 10-hydroxycamptothecin (HCPT) directly to glioma cells. The researchers modified HDL with T7 and dA7R peptides. In vitro studies showed that the T7/A7R-HDL particles had a higher affinity for both the BBB and glioma cells compared to single-ligand modified or unmodified HDL. In vivo, the T7/A7R-HDL particles loaded with HCPT demonstrated superior anti-glioma effects, reducing tumor growth and prolonging survival in mice with intracranial C6 tumors.

What are the potential next steps in the research and development of T7/A7R-HDL particles for brain cancer therapy?

Future research on dual-modified high-density lipoprotein (HDL) particles could focus on fully understanding the mechanisms of targeted delivery and exploring the application of T7/A7R-HDL in clinical settings. This includes assessing long-term efficacy, potential side effects, and scalability for human use. Additionally, researchers may investigate combining T7/A7R-HDL with other therapeutic strategies to enhance treatment outcomes for glioblastoma and other brain tumors. This innovative approach represents a significant step forward in developing more effective and less toxic treatments for brain tumors, potentially revolutionizing how these aggressive cancers are managed.