Nanoparticles for inducing Gaucher disease-like damage in cancer cells

doi:10.1038/s41565-024-01668-4

. 2024 May 13.

doi: 10.1038/s41565-024-01668-4. Online ahead of print.

Nanoparticles for inducing Gaucher disease-like damage in cancer cells

Chunyan Yue^#^{1

2

3}, Wenjing Lu^#^{1

2

3}, Shuxin Fan^#^{1

2

3}, Zhusheng Huang^{1

2

3}, Jiaying Yang^{1

2

3}, Hong Dong^{1

2

3}, Xiaojun Zhang^{1

2

3}, Yuxin Shang^{1

2

3}, Wenjia Lai⁴, Dandan Li^{1

2

3}, Tiejun Dong^{1

2

3}, Ahu Yuan^{1

2

3}, Jinhui Wu^{1

2

3}, Lifeng Kang⁵, Yiqiao Hu^{6

7

8}

Affiliations

¹ State Key Laboratory of Pharmaceutical Biotechnology, Medical School, Nanjing University, Nanjing, China.
² Institute of Drug R&D, School of Life Science, Nanjing University, Nanjing, China.
³ Jiangsu Key Laboratory for Nano Technology, Nanjing University, Nanjing, China.
⁴ CAS Key Laboratory of Standardization and Measurement for Nanotechnology, National Center for Nanoscience and Technology, Beijing, China.
⁵ School of Pharmacy, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
⁶ State Key Laboratory of Pharmaceutical Biotechnology, Medical School, Nanjing University, Nanjing, China. huyiqiao@nju.edu.cn.
⁷ Institute of Drug R&D, School of Life Science, Nanjing University, Nanjing, China. huyiqiao@nju.edu.cn.
⁸ Jiangsu Key Laboratory for Nano Technology, Nanjing University, Nanjing, China. huyiqiao@nju.edu.cn.

^# Contributed equally.

PMID: 38740934
DOI: 10.1038/s41565-024-01668-4

Nanoparticles for inducing Gaucher disease-like damage in cancer cells

Chunyan Yue et al. Nat Nanotechnol. 2024.

. 2024 May 13.

doi: 10.1038/s41565-024-01668-4. Online ahead of print.

Authors

Affiliations

¹ State Key Laboratory of Pharmaceutical Biotechnology, Medical School, Nanjing University, Nanjing, China.
² Institute of Drug R&D, School of Life Science, Nanjing University, Nanjing, China.
³ Jiangsu Key Laboratory for Nano Technology, Nanjing University, Nanjing, China.
⁴ CAS Key Laboratory of Standardization and Measurement for Nanotechnology, National Center for Nanoscience and Technology, Beijing, China.
⁵ School of Pharmacy, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
⁶ State Key Laboratory of Pharmaceutical Biotechnology, Medical School, Nanjing University, Nanjing, China. huyiqiao@nju.edu.cn.
⁷ Institute of Drug R&D, School of Life Science, Nanjing University, Nanjing, China. huyiqiao@nju.edu.cn.
⁸ Jiangsu Key Laboratory for Nano Technology, Nanjing University, Nanjing, China. huyiqiao@nju.edu.cn.

^# Contributed equally.

PMID: 38740934
DOI: 10.1038/s41565-024-01668-4

Abstract

Nutrient avidity is one of the most distinctive features of tumours. However, nutrient deprivation has yielded limited clinical benefits. In Gaucher disease, an inherited metabolic disorder, cells produce cholesteryl-glucoside which accumulates in lysosomes and causes cell damage. Here we develop a nanoparticle (AbCholB) to emulate natural-lipoprotein-carried cholesterol and initiate Gaucher disease-like damage in cancer cells. AbCholB is composed of a phenylboronic-acid-modified cholesterol (CholB) and albumin. Cancer cells uptake the nanoparticles into lysosomes, where CholB reacts with glucose and generates a cholesteryl-glucoside-like structure that resists degradation and aggregates into microscale crystals, causing Gaucher disease-like damage in a glucose-dependent manner. In addition, the nutrient-sensing function of mTOR is suppressed. It is observed that normal cells escape severe damage due to their inferior ability to compete for nutrients compared with cancer cells. This work provides a bioinspired strategy to selectively impede the metabolic action of cancer cells by taking advantage of their nutrient avidity.

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References

1. Bartman, C. R. et al. Slow TCA flux and ATP production in primary solid tumours but not metastases. Nature 614, 349–357 (2023). - PubMed - PMC - DOI
1. Ringel, A. E. et al. Obesity shapes metabolism in the tumor microenvironment to suppress anti-tumor immunity. Cell 183, 1848–1866 (2020). - PubMed - PMC - DOI
1. Faubert, B., Solmonson, A. & DeBerardinis, R. J. Metabolic reprogramming and cancer progression. Science 368, eaaw5473 (2020). - PubMed - PMC - DOI
1. Kanarek, N., Petrova, B. & Sabatini, D. M. Dietary modifications for enhanced cancer therapy. Nature 579, 507–517 (2020). - PubMed - DOI
1. Kim, J. & Guan, K.-L. mTOR as a central hub of nutrient signalling and cell growth. Nat. Cell Biol. 21, 63–71 (2019). - PubMed - DOI

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82204293/National Natural Science Foundation of China (National Science Foundation of China)

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[1] Bartman, C. R. et al. Slow TCA flux and ATP production in primary solid tumours but not metastases. Nature 614, 349–357 (2023). - PubMed - PMC - DOI

[2] Bartman, C. R. et al. Slow TCA flux and ATP production in primary solid tumours but not metastases. Nature 614, 349–357 (2023). - PubMed - PMC - DOI

[3] Ringel, A. E. et al. Obesity shapes metabolism in the tumor microenvironment to suppress anti-tumor immunity. Cell 183, 1848–1866 (2020). - PubMed - PMC - DOI

[4] Ringel, A. E. et al. Obesity shapes metabolism in the tumor microenvironment to suppress anti-tumor immunity. Cell 183, 1848–1866 (2020). - PubMed - PMC - DOI

[5] Faubert, B., Solmonson, A. & DeBerardinis, R. J. Metabolic reprogramming and cancer progression. Science 368, eaaw5473 (2020). - PubMed - PMC - DOI

[6] Faubert, B., Solmonson, A. & DeBerardinis, R. J. Metabolic reprogramming and cancer progression. Science 368, eaaw5473 (2020). - PubMed - PMC - DOI

[7] Kanarek, N., Petrova, B. & Sabatini, D. M. Dietary modifications for enhanced cancer therapy. Nature 579, 507–517 (2020). - PubMed - DOI

[8] Kanarek, N., Petrova, B. & Sabatini, D. M. Dietary modifications for enhanced cancer therapy. Nature 579, 507–517 (2020). - PubMed - DOI

[9] Kim, J. & Guan, K.-L. mTOR as a central hub of nutrient signalling and cell growth. Nat. Cell Biol. 21, 63–71 (2019). - PubMed - DOI

[10] Kim, J. & Guan, K.-L. mTOR as a central hub of nutrient signalling and cell growth. Nat. Cell Biol. 21, 63–71 (2019). - PubMed - DOI

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Nanoparticles for inducing Gaucher disease-like damage in cancer cells

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Nanoparticles for inducing Gaucher disease-like damage in cancer cells

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