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CHARACTERISTICS OF THE MXENE-ANTI-CEACAM1 COMPLEX FOR PHOTOTHERMAL TARGETED TREATMENT OF MELANOMA

Anastasia Konieva1, 2 *, Volodymyr Deineka3, 4, Veronika Zahorodna5, Oleksiy Gogotsi5, Irina Kube-Golovin1, Igor Iatsunskyi6, Gunther Wennemuth1, Maksym Pogorielov4, 3

1) University Hospital Essen, Department of Anatomy (Germany)

2) Biomedical Research Centre, Medical Institute, Sumy State University, Sumy (Ukraine)

3) University of Latvia, Riga (Latvia)

4) Sumy State University, Sumy (Ukraine)

5) Materials Research Center, Y-Carbon Ltd, Kyiv (Ukraine)

6) NanoBioMedical Centre, Adam Mickiewicz University (Poland)

* anastasiia.konieva@uk-essen.de

Local photothermal therapy (PTT) represents a promising non-invasive treatment modality. The operating principle of the PTT is based on the presence of optical absorbing agents, also known as photothermal agents (PTAs). The importance of the presence of PTAs is due to their ability to absorb and convert light energy into heat. Thus, tumor cells associated with PTAs are amenable to thermal ablation [1, 2]. In our study, we consider MXenes as PTAs for the photothermal ablation of melanoma [3]. To ensure the attachment of nanoparticles only to tumor cells, we developed an MXene-anti-CEACAM1 complex. Anti-CEACAM1 monoclonal antibody (mAb) exhibits specificity for a CEACAM1 molecule that is expressed on the surface of melanoma cells and can be used as a target for the treatment of melanoma [4]. The combination of MXenes and anti-CEACAM1 mAb emerges as a promising platform for the development of an innovative targeted treatment model for melanoma.

The aim of our study is the development of an MXene-anti-CEACAM1 mAb complex followed by its biological characterization with evaluation of the targeted photothermal effect in vitro using a NIR-I laser. 

Delaminated Ti3C2Tx MXenes were modified with polydopamine (PDA) with different thicknesses followed by human anti-CEACAM1 mAb immobilization. Biological characterization of the complex included determination of specificity (FACS, ELISA), affinity (FACS, bright field microscopy, IC50) and cross-reactivity (FACS).

Results of FACS and ELISA assays demonstrate high affinity and specificity to CEACAM1, while the MXene-PDA-anti-CEACAM1 mAb complex does not bind to other CEACAMs (CC3/CC5/CC6/CC8). Furthermore, increasing the thickness of the PDA layer does not affect the specificity and affinity of the complex.

Conclusion. Our results demonstrate the MXene-PDA-anti-CEACAM1 mAb complex is a promising model for a new model of targeted melanoma PTT. Improvements to this approach, such as surface modification of MXene with PDA and coupling with specific antibodies, could expand its applicability in the treatment of other cancers.


Keywords:

Ti3C2Tx MXene, cancer treatment, photothermal therapy, CEACAM1

Acknowledgements:

This research received support from the Horizon Europe Framework Programme (HORIZON) Call: HORIZON-MSCA-2021-SE-01 (Project #101086184) and MSCA4Ukraine project (Project #1232462), and supported by LRC grant No 2023/1-0243.

References:

[1] D. Zhi, T. Yang, J. O’Hagan, S. Zhang, and R. F. Donnelly, “Photothermal therapy,” Journal of Controlled Release, vol. 325, pp. 52–71, Sep. 2020, doi: 10.1016/j.jconrel.2020.06.032.

[2] X. Li, J. F. Lovell, J. Yoon, and X. Chen, “Clinical development and potential of photothermal and photodynamic therapies for cancer,” Nature Reviews Clinical Oncology, vol. 17, no. 11. 2020. doi: 10.1038/s41571-020-0410-2.

[3] Kyrylenko, S., Gogotsi, O., Baginskiy, I., Balitskyi, V., Zahorodna, V., Husak, Y., Yanko, I., Pernakov, M., Roshchupkin, A., Lyndin, M., Singer, B. B., Buranych, V., Pogrebnjak, A., Sulaieva, O., Solodovnyk, O., Gogotsi, Y., & Pogorielov, M. (2022). MXene-Assisted Ablation of Cells with a Pulsed Near-Infrared Laser. ACS Applied Materials & Interfaces, 14(25), 28683–28696. https://doi.org/10.1021/acsami.2c08678

[4] I. Helfrich and B. Singer, “Size Matters: The Functional Role of the CEACAM1 Isoform Signature and Its Impact for NK Cell-Mediated Killing in Melanoma,” Cancers (Basel), vol. 11, no. 3, p. 356, Mar. 2019, doi: 10.3390/cancers11030356.

Track: Nanobiomedical Research & Applications (NRA)
Presentation type: Poster Presentation
Status: Accepted for presentation