siRNA Delivery

Dendrimers are another class of siRNA delivery systems that have gained considerable attention due to their unique structural properties and biocompatibility. Dendrimers are highly branched, spherical, and monodisperse polymers with a central core, an inner shell, and an outer shell. They have well-defined sizes, shapes, and surface functionalities that can be tailored to optimize siRNA delivery.

Challenges of siRNA Delivery

Small interfering RNA (siRNA) has great potential as a therapeutic agent for various diseases, including cancer, viral infections, and genetic disorders. However, siRNA delivery remains a major challenge in the field of RNA interference (RNAi) therapy. Here are some of the challenges of siRNA delivery:

• Stability: siRNA is vulnerable to degradation by nucleases in the bloodstream and the extracellular environment, which can limit its efficacy.

• Specificity: siRNA needs to be delivered specifically to target cells or tissues, while avoiding off-target effects that can cause unintended side effects.
• Immune Response: siRNA can trigger an immune response, leading to the activation of innate immune cells and inflammation, which can limit its therapeutic potential.
• Delivery Barriers: siRNA cannot easily penetrate cell membranes, and delivery vehicles such as liposomes, nanoparticles, and viral vectors face several barriers, including clearance by the immune system and uptake by non-target cells.
• Dosage: Determining the appropriate dose of siRNA is challenging, as the optimal dose can vary depending on the target tissue and disease.
• Cost: Developing and producing safe and effective siRNA delivery vehicles can be expensive, limiting the accessibility of RNAi therapies to patients.

Addressing these challenges requires the development of safe and effective siRNA delivery methods that can overcome these barriers and achieve specific and efficient delivery of siRNA to target cells or tissues.

siRNA Delivery System

To overcome the challenges of siRNA delivery, researchers have developed various siRNA delivery systems that can protect siRNA from degradation and deliver it to target cells or tissues. Here are some examples of siRNA delivery systems:

Polymer-based Nanoparticles of Dendrimers as siRNA Delivery Systems

Dendrimers can bind to siRNA through electrostatic interactions, hydrogen bonding, or covalent linkage, and protect siRNA from nuclease degradation. Dendrimers can also facilitate siRNA uptake by cells through various mechanisms such as endocytosis and membrane fusion. Additionally, dendrimers can overcome the intracellular barriers that limit siRNA delivery to the cytoplasm, such as the endosomal escape. There are several types of dendrimers that have been investigated for siRNA delivery, including polyamidoamine (PAMAM), polypropyleneimine (PPI), and carbosilane dendrimers. PAMAM dendrimers are the most widely studied dendrimers for siRNA delivery due to their high transfection efficiency and low toxicity. One of the challenges of dendrimers as siRNA delivery systems is their toxicity. The positive charges on dendrimer surfaces that allow them to interact with siRNA can also cause cytotoxicity by disrupting cell membranes and inducing oxidative stress. Therefore, the design of dendrimers with appropriate surface chemistry and charge balance is critical to minimize their toxicity.

Amphiphilic dendrimer-mediated siRNA delivery to various immune cells, including T cells, microglia, and NK cells. (Chen J, et al., 2021)

How We Can Help

CD BioSciences is a specialized provider of dendrimer products and custom services. We are committed to speeding up the achievement of our customers' research goals with high quality and providing custom services to meet the specific needs of their studies. Our custom services and high-quality products will make a significant contribution to the success of your project. For more detailed information, please feel free to contact us or send us an inquiry directly.

Reference

1. Chen J.; et al. Synthesis and use of an amphiphilic dendrimer for siRNA delivery into primary immune cells. Nat Protoc. 2021, 16: 327-351.