Research in the Sailor Labs

Macrophage-targeting fusogenic porous silicon nanoparticles loaded with siIRF5 effectively protect infected mice (green) from a lethal S. aureus infection (Nat. Commun. 2018, 9, 1969. DOI: 10.1038/s41467-018-04390-7).

Reprogramming macrophages to treat infectious diseases. Motivated by the observation that many lung infections are lethal because they trigger an over-reaction of the immune system, these porous silicon nanoparticles deliver a gene therapeutic (siRNA against the IRF5 gene) that reprograms pro-inflammatory immune cells (macrophages) to temporarily suppress their inflammatory immune response in the lungs. In mouse models of lethal bacterial pneumonia, we found that this treatment gives the animals time to mount an effective endogenous immune response. The approach is enabled by three breakthroughs: a condenser chemistry that provides high mass loading of the siRNA therapeutic; a fusogenic nanoparticle system that can effectively avoid endocytosis and deliver the gene therapeutic directly into the cytosol of cells; and a targeting peptide (CRV) that makes the nanoparticle specific for the macrophage cells that need to be suppressed.
Collaboration with Sangeeta Bhatia at MIT, Ester Kwon at UC San Diego and Tambet Teesalu at the University of Tartu.

SEM image of porous silicon nanoparticles. The nanoparticles can contain biologic or small molecule therapeutics for treatment of various conditions. Scale bar is 1000 nm. These materials provide a non-toxic and biodegradable platform for drug delivery and medical diagnostic applications.
(Bioconjugate Chem. 2022, 33, 1685. DOI: 10.1021/acs.bioconjchem.2c00305) Photo Credit: Jinmyoung Joo, UCSD.

Peptide-targeted drug delivery. Using tissue-specific peptides grafted to the exterior of a porous silicon nanoparticle for treatment of traumatic brain injuries, diseases of the eye, and cancer. A major goal here is to increase the circulation time of therapeutic peptides such that they can be available in circulation at levels sufficient to bind to damaged tissues or receptors expressed in response to the trauma or disease. Our team is collaborating with University of Tartu Professor Tambet Teesalu, whose task in this project is to deploy in-vivo phage screening tools to discover new peptides that bind to tissues or receptors associated with the indication. The work also involves a collaboration with the company Aivocode, who is providing additional targeting and therapeutic peptides.
Collaboration with Ester Kwon at UC San Diego, Tambet Teesalu at the University of Tartu, Aivocode, and researchers from Battelle Memorial Institute.

Nano-cages of porous nanostructures to encapsulate and enhance the performance of enzymes and other catalytic payloads for selected medical, environmental remediation, and energy storage/harvesting applications. (Chem. Mater. 2023, 35, 10247. DOI: 10.1021/acs.chemmater.3c02637).

Armor-coated enzymes. There is a growing interest in nanomaterials that can encapsulate enzymes while retaining their ability to function under non-biologic conditions. Using porous silicon nanoparticles (pSiNPs) as the cage, we harness the aqueous chemistry of silicon to dynamically restructure the mesopore structure, immobilizing and confining the enzyme. A variety of functional enzymes can be used as guests: the bioluminescent reporter enzyme nanoluciferase (Nluc), hydrolytic enzymes for decontamination of toxins and toxicants, and proteolytic enzymes. Enzyme stability is typically improved – the caged materials can retain substantial activity under denaturing conditions that normally result in complete or near-complete loss of activity for the free enzyme.
Collaboration with Akif Tezcan at UC San Diego and researchers from Leidos, inc.