Nanoparticles for Uniform Nanowarming of Cryopreserved Organs

Enhances Organ Transplant Viability by Rewarming Without Damaging Temperature Gradients

These nanoparticles leverage biocompatible coating and exceptional aggregation resistance to permeate organs for cryopreservation and nanowarming. Organ transplants deliver lifesaving care to tens of thousands of Americans each year, but the demand for transplants is about ten times greater than the available supply, taking untold lives. One immediate solution is to increase the lifetime for organ preservation since over half of intact organs are not being preserved long enough for transplant. Cryopreservation of organs at low temperatures without ice formation can extend lifetimes, but many cryopreserved organs are damaged by the temperature gradients between their surface and their interior during rewarming. A process known as nanowarming avoids this problem by generating heat with nanoparticles distributed uniformly within the organ. However, many candidate nanoparticles clump together during cryopreservation, reducing heating uniformity and damaging organs.

Researchers at the University of Florida have developed a superparamagnetic iron oxide nanoparticle (SPION) whose layered polyethylene glycol (PEG) coating reduces aggregation and whose response to magnetic fields enables fast, controllable rewarming rates. Their PEG coating is also biocompatible, reducing toxicity to and preventing immediate clearance from tissue. Their magnetic properties also enable quantitative verification of removal after nanowarming using magnetic particle imaging.

Application

Magnetic nanoparticles with high colloidal stability for controlled, uniform rewarming of cryopreserved organs

Advantages

• Avoids aggregation for weeks even under drastic temperature changes, maintaining usefulness for the long-time scales and extreme conditions of the cryopreservation/rewarming cycle
• Uniformly permeates organs while maintaining strong magnetic response, achieving non-damaging warming from cryopreserved state that can be precisely controlled with an external magnetic field
• Easily removed by flushing the rewarmed organ with solution, leaving behind a viable organ
• Possesses optimal size and coating to avoid removal from the bloodstream for hours, allowing targeting of diseased tissue that will then light up during magnetic particle imaging

Technology

The intrinsic magnetism of SPIONs causes them to oscillate under alternating magnetic fields. When SPIONs are present in an organ, their oscillation adds heat, a process known as nanowarming. The ability of SPIONs to survive and spread out in the bloodstream, and of magnetic fields to travel through tissue, combine to ensure that nanowarming distributes heat uniformly throughout the tissue. Uniform heating is critical when rewarming cryopreserved organs (organs that have been vitrified into a non-crystalline solid, rather than simply frozen) that suffer damage under nonuniform heating. Introduction of SPIONs to the cryopreservant fluid during the vitrification process enables later rewarming, but the vitrification as well as the cryopreservant fluid itself present harsh conditions that can cause degradation or clumping of the SPIONs, ruining the uniformity of the heating.

The polymer coating of the SPIONs is the key to resisting degradation and clumping, and also impacts other desirable properties such as biocompatibility and blood circulation lifetime. While conventional PEG coatings contain exposed amines which cause clumping, these SPIONs coated with an additional layer of PEG have no exposed amines, preventing clumping for multiple weeks. This, along with their fast rewarming rates externally controllable via the alternating magnetic field, making these SPIONs ideal for the non-damaging rewarming of cryopreserved organs.