Biology subjects

Almunif, S.

Publications and source records attributed to Almunif, S..

4 recordsLinked to original sources

bioRxiv2026

Preserving Nanotherapy-Induced Allogeneic Murine Islet Graft Tolerance During Distal Methicillin-Resistant Staphylococcus aureus Skin Infection

Eliminating lifelong immunosuppression can make islet transplantation a durable alternative to insulin therapy for type 1 diabetes. As short-course tolerogenic regimens are developed to replace lifelong immunosuppression, it is critical to test their robustness against perturbations such as hospital-acquired infections, which transplant recipients routinely encounter. Herein, we investigated whether rapamycin-loaded polymersomes (rPS), a subcutaneous nanotherapy that induces long-term murine islet allograft survival, can preserve host defenses in a Methicillin-resistant Staphylococcus aureus (MRSA) skin infection, and whether the resulting immune response from this distal infection relative to graft location erodes rPS-induced tolerance. rPS maintained neutrophil antibacterial activity despite inhibiting oxidative mechanisms in vitro, and rPS-treated mice demonstrated normal recovery following MRSA challenge. However, MRSA skin infection caused a decline of ~43% in recipient survival for rPS-treated mice, despite surviving recipients retaining glucose-stimulated insulin responsiveness. This erosion of allograft acceptance coincided with a burst of IL-6 within 24h of the infection followed by elevated TNF-[a] and neutrophilia at 13 days post-infection. Combining rPS with a single dose of methylprednisolone reduced IL-6 and TNF- without altering neutrophilia, nearly doubling survival among infected recipients to 80%. Our findings demonstrate that partial dampening of inflammatory insults can restore superior islet allograft acceptance following perioperative infection.

bioengineering↗

bioRxiv2026

Nanotherapy-mediated biased antigen-presenting cell reprogramming supports T cell anergy to prevent type 1 diabetes

Engineering immune tolerance using endogenously expressed autoantigens could enable early intervention in autoimmune disease. Present therapies suppress T cells to slow disease progression. Here, we develop rapamycin-loaded poly(ethylene glycol)-b-poly(propylene sulfide) polymersomes (rPS) to modulate antigen-presenting cells (APCs) during disease-associated antigen presentation. The rPS morphology enables lymphatic drainage following subcutaneous administration to access APCs in draining lymph nodes. Treatment reduced APC costimulatory marker coexpression and shifted CD4+ T cells toward an FR4hi CD73hi anergic phenotype. In a type 1 diabetes (T1D) nonobese diabetic (NOD) mouse model, rPS significantly delayed disease onset relative to the standard of care and selectively prevented hyperglycemia. Mediation via APCs, rPS avoids adverse effects including transient lymphopenia. These findings demonstrate how biomaterial-directed drug delivery can reshape APC--T cell interactions, supporting an antigen-agnostic strategy for delaying autoimmune diabetes without systemic lymphocyte depletion.

bioengineering↗

bioRxiv2025

Enabling Organ- and Injury-Specific Nanocarrier Targeting via Surface-Functionalized PEG-b-PPS Micelles for Acute Kidney Injury

While nanomedicine holds great promise for kidney disease, targeted delivery remains a major challenge. Most nanocarriers rely on passive accumulation or epithelial-specific ligands, limiting their utility in complex, inflamed renal environments. In acute kidney injury (AKI), inflammation and vascular dysfunction play central roles, yet targeting strategies beyond the tubule remain underexplored. Here, dual-ligand micelles are developed to enhance nanocarrier localization to the inflamed kidney by simultaneously engaging both organ- and injury-specific cues. Poly(ethylene glycol)-block-poly(propylene sulfide) (PEG-b-PPS) micelles were engineered to display two peptide ligands: CLPVASC, which preferentially distributes to the kidney, and CYNTTTHRC, which binds selectively to inflamed endothelium. These targeting motifs were incorporated via lipid-anchored peptide amphiphiles, enabling modular surface functionalization without disrupting micelle morphology, size, or charge. In vitro, dual-targeted micelles demonstrated enhanced uptake by human endothelial cells exposed to hypoxia-reoxygenation. In vivo, following unilateral renal ischemia-reperfusion injury (IRI) in mice, targeted micelles achieved selective accumulation in the injured kidney, outperforming both non-targeted controls and contralateral kidneys. Off-target distribution to liver, lung, and spleen was markedly reduced, confirming the spatial precision of the dual-ligand approach. This strategy offers a scalable, modular, and biologically informed platform for precision delivery in AKI and related inflammatory conditions.

bioengineering↗

bioRxiv2023

Vaccination with mycobacterial lipid loaded nanoparticle leads to lipid antigen persistence and memory differentiation of antigen-specific T cells

Mycobacterium tuberculosis (Mtb) infection elicits both protein and lipid antigen-specific T cell responses. However, the incorporation of lipid antigens into subunit vaccine strategies and formulations has been underexplored, and the characteristics of vaccine-induced Mtb lipid-specific memory T cells have remained elusive. Mycolic acid (MA), a major lipid component of the Mtb cell wall, is presented by human CD1b molecules to unconventional T cell subsets. These MA-specific CD1b-restricted T cells have been detected in the blood and disease sites of Mtb-infected individuals, suggesting that MA is a promising lipid antigen for incorporation into multicomponent subunit vaccines. In this study, we utilized the enhanced stability of bicontinuous nanospheres (BCN) to efficiently encapsulate MA for in vivo delivery to MA-specific T cells, both alone and in combination with an immunodominant Mtb protein antigen (Ag85B). Pulmonary administration of MA-loaded BCN (MA-BCN) elicited MA-specific T cell responses in humanized CD1 transgenic mice. Simultaneous delivery of MA and Ag85B within BCN activated both MA- and Ag85B-specific T cells. Notably, pulmonary vaccination with MA-Ag85B-BCN resulted in the persistence of MA, but not Ag85B, within alveolar macrophages in the lung. Vaccination of MA-BCN through intravenous or subcutaneous route, or with attenuated Mtb likewise reproduced MA persistence. Moreover, MA-specific T cells in MA-BCN-vaccinated mice differentiated into a T follicular helper-like phenotype. Overall, the BCN platform allows for the dual encapsulation and in vivo activation of lipid and protein antigen-specific T cells and leads to persistent lipid depots that could offer long-lasting immune responses.

immunology↗