RESEARCH PROGRESS

Nanotechnology and combined strategies to enhance local immunomodulation for treatment of Type 1 Diabetes

In the quest to enhance the lives of those suffering from T1D, Dr. Diana Velluto, Research Assistant Professor in the Department of Surgery at the Diabetes Research Institute, University of Miami School of Medicine, is making incredible advances. Her work centers on the use of innovative nanotechnology to transform how we approach diabetes treatment.

The Challenge in T1D Treatment: For patients with T1D, transplanting healthy pancreatic cells can be a game-changer, offering better blood sugar control and protection against severe hypoglycemia. However, these transplants require powerful immunosuppressive drugs to prevent rejection, leading to serious side effects like kidney damage, increased risk of infection, and harm to the transplanted cells themselves.

Dr. Velluto’s Solution: Nanotechnology: Dr. Velluto’s lab is at the forefront of developing nanotechnologies for targeted immunotherapies. These therapies aim to shield the transplanted cells from the host immune response, enhancing their survival without the need for systemic immunosuppression.

How Does It Work? Nanotechnology uses tiny particles, no larger than a virus, to deliver drugs directly to the target area. These nanoparticles, named Drug-Integrating Amphiphilic Nano-Assemblies (DIANAs), are specially designed to carry drugs in a controlled and safe manner. By adjusting their chemical properties, Dr. Velluto’s team can fine-tune how these nanoparticles release medication, enhancing efficacy and reducing toxicity.

Successful Applications and Future Horizons: Dr. Velluto has already achieved remarkable success with these nanoparticles. For example, using DIANAs to deliver Cyclosporine A, an immunosuppressant, led to a significant increase in drug solubility and a reduction in the dose and frequency needed. Another application involves Dexamethasone, an anti-inflammatory drug, which showed enhanced stability and targeted delivery to inflammation sites.

Particularly innovative is her idea to explore DIANA nanoparticles in combination with (i) stem cell therapy or (ii) graphene derivatized materials, to maximize local immunomodulation.

Currently, Dr. Velluto is exploring the use of DIANAs in combination with stem cell therapy and graphene oxide-derivatized materials (GO-DIANA) to maximize local immune modulation. These innovative approaches could revolutionize the treatment of T1D, offering a more effective, safer alternative to current methods.

The Impact: Dr. Velluto’s work signifies a major leap forward in diabetes care. By focusing on local treatment, her nanotechnology strategies aim to minimize the adverse effects associated with traditional systemic immunosuppression. This technology has the potential to make cell transplantation a more viable and safer option for T1D patients, bringing us closer to a future where diabetes can be managed more effectively and with fewer complications.

CURRENT RESEARCH: Dr. Velluto is currently working on different projects and several collaborations on the use of Drug-Integrating Amphiphilic Nano-Assemblies (DIANAs) and strategies to enhance local immunomodulation: “Passive Targeted and Sustained Delivery of Dexamethasone and its soft-drug derivatives using nanomicelles”, “Nanomaterial Engineered Stem Cells For Enhanced Immune Therapies In Pancreatic Islet Transplantation” and “Graphene Oxide Functionalized Drug-Integrating Amphiphilic Nano-Assemblies (GO-DIANA) with High Potential Application in the Diabetes Treatment”.

Nanotechnology-Based Therapies for Type 1 Diabetes (T1D): 1. Material Forming Nanoparticles: Depiction of the initial assembly of nanomaterials, showcasing the self-organization of polymers into nanoparticles. This stage involves the synthesis of biocompatible and biodegradable nanoparticles, which are engineered for optimal size and shape to facilitate drug loading and targeted delivery. 2. Drug Loading Nanoparticles: Illustration of therapeutic agents, such as immunomodulators, being encapsulated within the nanoparticles. This encapsulation is designed to protect the drug from degradation, enhance its solubility, and allow for precise control over its release profile. 3. Drug-Nanoparticle Inclusion into Cells: Demonstration of the final stage where drug-loaded nanoparticles are taken up by target cells. The nanoparticles are designed to preferentially accumulate at sites of inflammation (like the transplanted pancreatic islets) and release their therapeutic payload intracellularly to exert the desired immunomodulatory effects.

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