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LXR inhibitor SR9243-loaded immunoliposomes modulate lipid metabolism and stemness in colorectal cancer cells

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Abstract

Reprogrammed metabolism and active stemness contribute to cancer stem cells’ (CSCs) survival and tumorigenesis. LXR signaling regulates the metabolism of different cancers. A selective LXR inhibitor, SR9243 (SR), can target and eradicate non-CSC tumor cells. CD133 is a stem marker in solid tumors-associated CSCs within the active lipogenesis, and anti-CD133 mAb targeting liposomal drug delivery systems expected to increase drug internalization and improve the therapeutic efficacy of poor-in water solubility drugs, e, g., SR. In this study, anti-CD133 mAbs-targeted Immunoliposomes (ILipo) were developed for specific delivery of SR into MACS-enriched CD133 + CSCs and induce their functional effects. Results have shown that ILipo having an average size of 64.79 nm can encapsulate SR in maximum proportion, and cell association studies have shown cationic ILipo and targeting CD133 provide the CSCs binding. Also, FCM analysis of RhoB has demonstrated that the ILipo uptake was higher in CD133 + CSCs than in the non-targeted liposomes. ILipo-SR was significantly more toxic in CD133 + CSCs compared to the free SR and non-targeted ones. More efficient than Lipo-SR, ILipo-SR improved the reduction of clonogenicity, stemness, and lipogenesis in CD133 + CSCs in vitro, boosted ROS generation, and induced apoptosis. Our study revealed the dual targeting of CD133 and LXR appears to be a promising strategy for targeting CD133 + CSCs-presenting dynamic metabolism and self-renewal potentials.

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Data availability

The data that support the findings of this study are available from the corresponding authors upon reasonable request.

Abbreviations

CSC:

Cancer stem cell

CLs:

Cationic liposomes

DOPE:

Dioleoyl phosphatidylethanolamine

DOTAP:

1,2-Dioleoyl-3-trimethylammonium-propane

FASN:

Fatty acid synthase

ILipo:

Immunoliposomes

LXR:

Liver X nuclear receptor

MACS:

Magnetic activated cell sorting

SCD1:

Stearoyl-CoA desaturase-1

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Acknowledgements

The authors appreciate the personnel of Drug Applied Research Center for help and guide.

Funding

This work was financially supported by Tabriz University of Medical Sciences (Hassan Dianat-Moghadam Ph.D. Thesis. Approval ID: IR.TBZMED.VCR.REC.1397.097).

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Authors and Affiliations

  1. Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

    Hassan Dianat-Moghadam & Mahammad Nouri

  2. Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

    Hassan Dianat-Moghadam

  3. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Soheil Abbasspour-Ravasjani & Hamed Hamishehkar

  4. Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Hassan Dianat-Moghadam, Reza Rahbarghazi & Mahammad Nouri

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  1. Hassan Dianat-Moghadam
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Contributions

HDM, and SAR performed experiments and prepared draft. MN, RR, and HH designed and supervised the study. All the authors read and approved the final manuscript.

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Correspondence to Hassan Dianat-Moghadam or Mahammad Nouri.

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Dianat-Moghadam, H., Abbasspour-Ravasjani, S., Hamishehkar, H. et al. LXR inhibitor SR9243-loaded immunoliposomes modulate lipid metabolism and stemness in colorectal cancer cells. Med Oncol 40, 156 (2023). https://doi.org/10.1007/s12032-023-02027-4

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  • DOI: https://doi.org/10.1007/s12032-023-02027-4

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