Chongfan Technology
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17
2024
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Sun Tianmeng/Zhang Yuning team of Jilin University published a review of nanocarriers for targeted drug delivery in vascular system focusing on endothelial cells
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Endothelial cells (ECs) play a key role in maintaining vascular health, regulating hemodynamics, and regulating inflammatory responses. Nanocarriers have the transformative potential for precise drug delivery within the vasculature, particularly to endothelial cells for therapeutic purposes. However, the complex interactions between vascular endothelial cells and nanocarriers pose major challenges for the development and clinical translation of nanocarriers.
On October 12, 2024, Sun Tianmeng and Zhang Yuning of Jilin University jointly communicatedJournal of Nanobiotechnology Published online entitled“Nanocarriers for targeted drug delivery in the vascular system: focus on endothelium”Review of the research,This review describes the latest advances and key strategies for drug delivery to vascular endothelial cells using nanocarriers. It is suggested that nanocarriers can enhance the targeting specificity of ECs and improve the drug internalization efficiency by precise physical and chemical design and surface modification.
The review also details the application of nanocarriers specifically designed for ECs in the treatment of cardiovascular diseases, cancer metastasis and inflammatory diseases. Despite these advances, safety issues, the complexity of the in vivo process, and the challenge of achieving subcellular drug delivery remain significant hurdles for nanocarriers to effectively target ECs.A comprehensive understanding of endothelial cell biology and its interaction with nanocarriers is essential to realize the full potential of targeted drug delivery systems.
Nanocarriers have become a crucial carrier in modern drug therapy due to their efficient drug delivery, targeting specificity and controlled release characteristics.Recent advances in nanocarrier technology provide new strategies for improving the efficacy and safety of regular drugs. Despite these benefits, the controlled distribution and metabolism of nanomedicine in the body remains a challenge. A major problem is the rapid clearance of nanocarriers from the blood, which hinders the maintenance of effective drug concentrations in the target tissue. Vascular endothelial cells are crucial in this process because they not only affect the circulation time of nanocarriers in the blood, but also affect their distribution in tissues. As an integral part of the vascular wall, endothelial cells are responsible for regulating blood flow, vascular permeability and inflammatory response. In various diseases, including atherosclerosis and cancer, endothelial dysfunction is key, making these cells a key target or key factor in influencing drug efficacy. Recent studies have shown that for most nanocarriers, ECs located outside the target tissue are primarily responsible for their systemic clearance. In a healthy vascular system, endothelial cells promote the rapid clearance of nanocarriers from the blood by interacting with macrophages and the reticuloendothelial system. This clearance mechanism limits the precise accumulation of nanomedicine in the target tissue, reducing their therapeutic concentration and ultimately affecting clinical outcomes.Therefore, optimizing the pharmacokinetics of nanocarriers requires minimizing their interaction with endothelial cells in healthy blood vessels to prolong circulation time and enhance delivery to the target.
In contrast, in diseased tissues, endothelial cells can promote the accumulation of nanocarriers, thereby improving the therapeutic effect.For example, in tumor therapy, tumor ECs are traditionally thought to exhibit abnormal permeability, referred to as the enhanced permeability and retention effect (EPR), which facilitates nanocarrier entry into the tumor microenvironment. However, the large size of nanocarriers and the structural characteristics of tumors may hinder their diffusion and penetration, resulting in unsatisfactory therapeutic effects. By studying the interaction between nanocarriers and tumor ECs, a new method to improve the efficiency of drug delivery based on the mechanism of endocytosis has been proposed. Taking advantage of the high expression of gamma-glutamyltransferase (GGT) on tumor endothelial cells and adjacent tumor cells, they developed a strategy involving GGT-reactive polymer nanocarriers to convert passive diffusion into active transport.This approach enhances the interaction between the nanocarriers and tumor endothelial cells, resulting in a significant anti-tumor effect.
In the case of vascular disease, in order to improve the therapeutic effect, it is important to strengthen the interaction between the nanocarriers and the diseased endothelial cells.By specifically targeting molecular tags on the surface of ECs, nanocarriers can selectively accumulate in pathological tissues, thereby increasing drug concentration while minimizing side effects in non-target tissues. In cardiovascular diseases, including atherosclerosis and hypertension, endothelial dysfunction is closely related to disease progression, resulting in significant changes in the expression levels of various molecules on the surface of EC. These changes provide potential therapeutic targets. The shape, size, ligand density and other characteristics of the nanocarriers can be adjusted to optimize the design of nanocarriers targeting endothelial cells, thereby improving adhesion and penetration, thereby improving the therapeutic effect.Therefore, it is very important to understand the interaction mode between nanocarriers and endothelial cells and formulate corresponding regulation strategies to improve the therapeutic effect of nanocarriers.
After entering the vascular system, nanocarriers can interact with endothelial cells, potentially affecting drug delivery efficiency and inducing cellular stress responses.In some cases, nanocarriers may exhibit toxicity to vascular endothelial cells, leading to acute or chronic inflammation. For example, certain metals, such as silver, zinc oxide nanoparticles or cationic polymeric materials such as polyethyleneimine (PEI), have been reported to induce oxidative stress at elevated concentrations of ECs or prolonged exposure, leading to membrane damage and apoptosis. This cellular damage not only impairs the integrity of blood vessels, but also triggers a cascade of inflammatory responses that further impair the progression of the disease. To mitigate these problems, researchers are developing strategies to reduce the toxicity of ECs in people. One approach involves surface modification to minimize direct contact between the nanocarriers and ECs, thereby reducing toxic reactions. For example, polyethylene glycol (PEG) modification can greatly improve the biocompatibility of people, thereby reducing the interaction with ECs.In addition, the development of controlled-release nanocarriers that gradually release the drug to minimize the direct impact on cells is another strategy to reduce toxicity.
Investigating the critical role of ECs in people and their targeting strategies provides substantial research value in enhancing the therapeutic efficacy and safety of nanomedicine.Effective targeting of endothelial cells with nanocarriers requires a comprehensive understanding of the complex mechanisms of endothelial uptake, identification of factors that influence the interaction of nanocarriers with endothelial cells, and implementation of strategies to improve specificity and efficiency. The purpose of this review is to summarize and analyze recent advances in endothelial cell-targeted drug delivery using nanocarriers, and to discuss design strategies, challenges, and future directions.In addition, it will provide comprehensive insights and references to facilitate understanding of the interactions between people and ECs, as well as the development of regulatory approaches and strategies.
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