A novel therapy to ameliorate nitrogen mustard-induced limbal stem cell deficiency using lipoprotein-like nanoparticles

Elif Kayaalp Nalbant; Timothy J. Feliciano; Aliakbar Mohammadlou; Vincent L. Xiong; Jacquelyn E. Trujillo; Andrea E. Calvert; Nihal Kaplan; Parisa Foroozandeh; Jayden Kim; Emma M. Bai; Xiaolin Qi; Fernando Tobias; Eric W. Roth; Vinayak P Dravid; Kurt Lu; Son Binh T. Nguyen; C. Shad Thaxton; Han Peng; Robert M Lavker

doi:10.1038/s41536-025-00402-5

A novel therapy to ameliorate nitrogen mustard-induced limbal stem cell deficiency using lipoprotein-like nanoparticles

Elif Kayaalp Nalbant, Timothy J. Feliciano, Aliakbar Mohammadlou, Vincent L. Xiong, Jacquelyn E. Trujillo, Andrea E. Calvert, Nihal Kaplan, Parisa Foroozandeh, Jayden Kim, Emma M. Bai, Xiaolin Qi, Fernando Tobias, Eric W. Roth, Vinayak P Dravid, Kurt Lu, Son Binh T. Nguyen^*, C. Shad Thaxton^*, Han Peng^*, Robert M Lavker^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Chronic corneal inflammation, a component of sulfur mustard (SM) and nitrogen mustard (NM) injuries frequently leads to limbal stem cell deficiency (LSCD), which can compromise vision. Corneal conjunctivalization, neovascularization, and persistent inflammation are hallmarks of LSCD. Ocular exposure to SM and NM results in an acute and delayed phase of corneal disruption, culminating in LSCD. Available therapies for mustard keratopathy (e.g., topical corticosteroids) often have adverse side effects, and generally are ineffective in preventing the development of LSCD. We developed a novel, optically transparent HDL nanoparticle (NP) with an organic core (oc) molecular scaffold. This unique oc-HDL NP: (i) markedly improved corneal haze during the acute and delayed phases in vivo; (ii) significantly reduced the inflammatory response; and (iii) blunted conjunctivalization and corneal neovascularization during the delayed phase. These findings strongly suggest that our HDL NP is an ideal treatment for mustard keratopathy and other chronic corneal inflammatory diseases.

Original language	English (US)
Article number	14
Journal	npj Regenerative Medicine
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41536-025-00402-5
State	Published - Dec 2025

Funding

Nikon CAM: Imaging work was performed at the Northwestern University Center for Advanced Microscopy (RRID: SCR_020996) generously supported by NCI CCSG P30 CA060553 awarded to the Robert H Lurie Comprehensive Cancer CenterIMSERC: MALDI work made use of the IMSERC (RRID:SCR_017874) MS facility at Northwestern University, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-2025633), the State of Illinois, and the International Institute for Nanotechnology (IIN). ANTEC: Circular Dichroism spectroscopy was performed in the Analytical BioNanoTechnology Equipment Core Facility of the Simpson Querrey Institute for BioNanotechnology at Northwestern University. ANTEC receives partial support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-2025633) and Feinberg School of Medicine, Northwestern University.NU-BIF: Confocal microscopy was performed at the Biological Imaging Facility at Northwestern University (RRID:SCR_017767), graciously supported by the Chemistry for Life Processes Institute, the NU Office for Research. Research reported in this publication was supported by the National Institutes of Health Chemical Countermeasures Research Program (CCRP) executed by the National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and the National Institutes of Health Office of the Director (NIH OD) under award number U54AR079795 (K.Q.L., H.P., R.M.L., E.F., T.J.F., J.E.T., N.K., V.D., S.T.N., and C.S.T.). This research was also supported by National Institutes of Health grant EY019463 (R.M.L.), National Institutes of Health grants EY032922, EY028560, EY036320 (H.P.), National Institutes of Health grant T32GM008152 (T.J.F.), and National Institutes of Health grant F31AR081685 (J.E.T.).

ASJC Scopus subject areas

Medicine (miscellaneous)
Biomedical Engineering
Developmental Biology
Cell Biology

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Kayaalp Nalbant, E., Feliciano, T. J., Mohammadlou, A., Xiong, V. L., Trujillo, J. E., Calvert, A. E., Kaplan, N., Foroozandeh, P., Kim, J., Bai, E. M., Qi, X., Tobias, F., Roth, E. W., Dravid, V. P., Lu, K., Nguyen, S. B. T., Shad Thaxton, C., Peng, H., & Lavker, R. M. (2025). A novel therapy to ameliorate nitrogen mustard-induced limbal stem cell deficiency using lipoprotein-like nanoparticles. npj Regenerative Medicine, 10(1), Article 14. https://doi.org/10.1038/s41536-025-00402-5

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title = "A novel therapy to ameliorate nitrogen mustard-induced limbal stem cell deficiency using lipoprotein-like nanoparticles",

abstract = "Chronic corneal inflammation, a component of sulfur mustard (SM) and nitrogen mustard (NM) injuries frequently leads to limbal stem cell deficiency (LSCD), which can compromise vision. Corneal conjunctivalization, neovascularization, and persistent inflammation are hallmarks of LSCD. Ocular exposure to SM and NM results in an acute and delayed phase of corneal disruption, culminating in LSCD. Available therapies for mustard keratopathy (e.g., topical corticosteroids) often have adverse side effects, and generally are ineffective in preventing the development of LSCD. We developed a novel, optically transparent HDL nanoparticle (NP) with an organic core (oc) molecular scaffold. This unique oc-HDL NP: (i) markedly improved corneal haze during the acute and delayed phases in vivo; (ii) significantly reduced the inflammatory response; and (iii) blunted conjunctivalization and corneal neovascularization during the delayed phase. These findings strongly suggest that our HDL NP is an ideal treatment for mustard keratopathy and other chronic corneal inflammatory diseases.",

author = "{Kayaalp Nalbant}, Elif and Feliciano, {Timothy J.} and Aliakbar Mohammadlou and Xiong, {Vincent L.} and Trujillo, {Jacquelyn E.} and Calvert, {Andrea E.} and Nihal Kaplan and Parisa Foroozandeh and Jayden Kim and Bai, {Emma M.} and Xiaolin Qi and Fernando Tobias and Roth, {Eric W.} and Dravid, {Vinayak P} and Kurt Lu and Nguyen, {Son Binh T.} and {Shad Thaxton}, C. and Han Peng and Lavker, {Robert M}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = dec,

doi = "10.1038/s41536-025-00402-5",

language = "English (US)",

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Kayaalp Nalbant, E, Feliciano, TJ, Mohammadlou, A, Xiong, VL, Trujillo, JE, Calvert, AE, Kaplan, N, Foroozandeh, P, Kim, J, Bai, EM, Qi, X, Tobias, F, Roth, EW, Dravid, VP , Lu, K , Nguyen, SBT , Shad Thaxton, C , Peng, H & Lavker, RM 2025, 'A novel therapy to ameliorate nitrogen mustard-induced limbal stem cell deficiency using lipoprotein-like nanoparticles', npj Regenerative Medicine, vol. 10, no. 1, 14. https://doi.org/10.1038/s41536-025-00402-5

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T1 - A novel therapy to ameliorate nitrogen mustard-induced limbal stem cell deficiency using lipoprotein-like nanoparticles

AU - Kayaalp Nalbant, Elif

AU - Feliciano, Timothy J.

AU - Mohammadlou, Aliakbar

AU - Xiong, Vincent L.

AU - Trujillo, Jacquelyn E.

AU - Calvert, Andrea E.

AU - Kaplan, Nihal

AU - Foroozandeh, Parisa

AU - Kim, Jayden

AU - Bai, Emma M.

AU - Qi, Xiaolin

AU - Tobias, Fernando

AU - Roth, Eric W.

AU - Dravid, Vinayak P

AU - Lu, Kurt

AU - Nguyen, Son Binh T.

AU - Shad Thaxton, C.

AU - Peng, Han

AU - Lavker, Robert M

PY - 2025/12

Y1 - 2025/12

N2 - Chronic corneal inflammation, a component of sulfur mustard (SM) and nitrogen mustard (NM) injuries frequently leads to limbal stem cell deficiency (LSCD), which can compromise vision. Corneal conjunctivalization, neovascularization, and persistent inflammation are hallmarks of LSCD. Ocular exposure to SM and NM results in an acute and delayed phase of corneal disruption, culminating in LSCD. Available therapies for mustard keratopathy (e.g., topical corticosteroids) often have adverse side effects, and generally are ineffective in preventing the development of LSCD. We developed a novel, optically transparent HDL nanoparticle (NP) with an organic core (oc) molecular scaffold. This unique oc-HDL NP: (i) markedly improved corneal haze during the acute and delayed phases in vivo; (ii) significantly reduced the inflammatory response; and (iii) blunted conjunctivalization and corneal neovascularization during the delayed phase. These findings strongly suggest that our HDL NP is an ideal treatment for mustard keratopathy and other chronic corneal inflammatory diseases.

AB - Chronic corneal inflammation, a component of sulfur mustard (SM) and nitrogen mustard (NM) injuries frequently leads to limbal stem cell deficiency (LSCD), which can compromise vision. Corneal conjunctivalization, neovascularization, and persistent inflammation are hallmarks of LSCD. Ocular exposure to SM and NM results in an acute and delayed phase of corneal disruption, culminating in LSCD. Available therapies for mustard keratopathy (e.g., topical corticosteroids) often have adverse side effects, and generally are ineffective in preventing the development of LSCD. We developed a novel, optically transparent HDL nanoparticle (NP) with an organic core (oc) molecular scaffold. This unique oc-HDL NP: (i) markedly improved corneal haze during the acute and delayed phases in vivo; (ii) significantly reduced the inflammatory response; and (iii) blunted conjunctivalization and corneal neovascularization during the delayed phase. These findings strongly suggest that our HDL NP is an ideal treatment for mustard keratopathy and other chronic corneal inflammatory diseases.

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A novel therapy to ameliorate nitrogen mustard-induced limbal stem cell deficiency using lipoprotein-like nanoparticles

Abstract

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