Nanoreporter Identifies Lysosomal Storage Disease Lipid Accumulation Intracranially

Merav Antman-Passig, Zvi Yaari, Dana Goerzen, Rooshi Parikh, Savannah Chatman, Lauren E. Komer, Chen Chen, Emma Grabarnik, Mickael Mathieu, Adriana Haimovitz-Friedman, Daniel A. Heller

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Dysregulated lipid metabolism contributes to neurodegenerative pathologies and neurological decline in lysosomal storage disorders as well as more common neurodegenerative diseases. Niemann-Pick type A (NPA) is a fatal neurodegenerative lysosomal storage disease characterized by abnormal sphingomyelin accumulation in the endolysosomal lumen. The ability to monitor abnormalities in lipid homeostasis intracranially could improve basic investigations and the development of effective treatment strategies. We investigated the carbon nanotube-based detection of intracranial lipid content. We found that the near-infrared emission of a carbon nanotube-based lipid sensor responds to lipid accumulation in neuronal and in vivo models of NPA. The nanosensor detected lipid accumulation intracranially in an acid sphingomyelinase knockout mouse via noninvasive near-infrared spectroscopy. This work indicates a tool to improve drug development processes in NPA, other lysosomal storage diseases, and neurodegenerative diseases.

Original languageEnglish
Pages (from-to)10687-10695
Number of pages9
JournalNano Letters
Volume23
Issue number23
DOIs
StatePublished - 13 Dec 2023
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2023 American Chemical Society.

Funding

We thank the Richard Kolesnick Lab for their generous gift of ASMKO MEF cells and special thanks to Tambudzai Shamu for technical assistance. We thank Prakrit Jena for the image analysis code and fruitful discussions, and Prakrit Jena and Daniel Roxbury for thier assistance with images. We thank Zhigang Zhang from the Epidemiology-Biostatistics department for helping with statistical analysis of animal studies. We thank the staff of the Molecular Cytology Core Facility (MCCF) at Memorial Sloan Kettering Cancer Center for AFM imaging, live-cell confocal microscopy, and tissue sectioning and preparation. We especially acknowledge Biran Wang, Afsar Barlas, Ning Fan, Yevgeniy Romin, and Eric Chan. We thank Michelle Saoi from the Donald B. and Catherine C. Marron Cancer Metabolism Center at Memorial Sloan Kettering for the lipidomic profiling. This work was supported in part by the NCI (Cancer Center Support Grant P30-CA008748), NINDS (R01-NS116353 R01-NS122987), the National Science Foundation CAREER Award (1752506), the Ara Parseghian Medical Research Fund, the Expect Miracles Foundation - Financial Services Against Cancer, the Louis and Rachel Rudin Foundation, Emerson Collective, MSK’s Cycle for Survival’s Equinox Innovation Award in Rare Cancers, Mr. William H. Goodwin and Mrs. Alice Goodwin and the Commonwealth Foundation for Cancer Research, and the Experimental Therapeutics Center of Memorial Sloan Kettering Cancer Center. R.P was supported by NIH Grant (U54CA132378). Z.Y. was supported by the Ann Schreiber Mentored Investigator Award (Ovarian Cancer Research Fund) and Young Investigator 2019 (Kaleidoscope of Hope). M.A.P. was supported by the Joe W. and Dorothy Dorsett Brown Foundation. This work was supported in part by the NCI (Cancer Center Support Grant P30-CA008748), NINDS (R01-NS116353 R01-NS122987), the National Science Foundation CAREER Award (1752506), the Ara Parseghian Medical Research Fund, the Expect Miracles Foundation - Financial Services Against Cancer, the Louis and Rachel Rudin Foundation, Emerson Collective, MSK’s Cycle for Survival’s Equinox Innovation Award in Rare Cancers, Mr. William H. Goodwin and Mrs. Alice Goodwin and the Commonwealth Foundation for Cancer Research, and the Experimental Therapeutics Center of Memorial Sloan Kettering Cancer Center. R.P was supported by NIH Grant (U54CA132378). Z.Y. was supported by the Ann Schreiber Mentored Investigator Award (Ovarian Cancer Research Fund) and Young Investigator 2019 (Kaleidoscope of Hope). M.A.P. was supported by the Joe W. and Dorothy Dorsett Brown Foundation.

FundersFunder number
Donald B. and Catherine C. Marron Cancer Metabolism Center
National Science Foundation1752506
National Institutes of HealthU54CA132378
National Cancer InstituteP30-CA008748
National Institute of Neurological Disorders and StrokeR01-NS116353 R01-NS122987
Joe W. and Dorothy Dorsett Brown Foundation
Ovarian Cancer Research Fund
Commonwealth Foundation for Cancer Research Foundation
Ara Parseghian Medical Research Fund
Expect Miracles Foundation

    Keywords

    • Niemann−Pick
    • biosensor
    • carbon nanomaterials
    • neurodegenerative disease
    • sphingomyelin

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