Treating laryngeal cancer with conventional radiotherapy, chemotherapy, and surgery has significant side effects. To this end, multifunctional nanoplatforms with collaborative therapeutic efficiency can be used to overcome these side effects.
Study: Preparation of NIR-sensitive, photothermal and photodynamic multi-functional Mxene nanosheets for laryngeal cancer therapy by regulating mitochondrial apoptosis. Image Credit: 9nong/Shutterstock.com
In an article recently published in the journal Materials and Design, researchers proposed a near-infrared (NIR) responsive IR780-modified Mxene (Ti3C2@IR780) nanosheet as a therapeutic strategy for targeted therapy. This strategy executed synergistic functions of photodynamic (PDT) therapy, photothermal (PTT) therapy, and mitochondrial pathway apoptosis.
The results obtained from electron spin resonance revealed the production of singlet linear oxygen from Ti3C2@IR780 for PDT. Furthermore, the molecular biology studies confirmed the excellent ability of Ti3C2@IR780 to generate reactive oxygen species (ROS) that could disrupt mitochondrial function, causing apoptosis in cancer cells.
Nanomaterials in Cancer Treatment
Laryngeal cancer is a malignant tumor affecting the head and neck, causing severe psychological and physical discomfort. The conventional treatment methods for this cancer include surgery and radiotherapy in combination. However, unfavorable effects of radiotherapy and complications in surgery result in high metastasis rates and high reoccurrence of laryngeal cancer.
Nanomaterials-based phototherapy techniques gained considerable attention due to their non-invasive ability, high selectivity, and low systemic toxicity. Thus, developing NIR light-sensitive nanoplatforms is desirable for inhibiting tumor growth, targeting tumor cells, and modulating the phototherapy in laryngeal cancer treatment.
Under NIR irradiation, MXene exhibits intense absorptivity and superior histological penetration ability and can work as a photothermal medium in treating the tumor. Moreover, MXene is inefficient in tumor aggregation. Its ease of functionalization and high surface-to-volume ratio are the two aspects with tuning prospects to improve therapeutic efficiency.
IR780 is a NIR dye with inherent tumor-targeting ability in its natural structure. However, due to the limitations of hydrophobicity, concentration-based IR780 monomer aggregation, its therapeutic efficiency is compromised.
Ti3C2@IR780 Nanosheets for Treating Laryngeal Cancer
In the present study, the researchers chose two-dimensional MXene as photothermal material. They loaded the IR780 photosensitizer (PS) onto MXene and fabricated Ti3C2@IR780 nanosheet to treat laryngeal cancer. The constructed Ti3C2@IR780 nanosheet was a multifunctional nanoplatform with NIR photosensitivity utilized to treat laryngeal cancer.
The ultraviolet (UV) absorption spectrum of IR780 exhibited a characteristic absorption peak at 774 nanometers. After binding to MXene, the formed Ti3C2@IR780 had an enhanced degree of conjugation and showed an intense and broad absorption peak at 817 nanometers, which confirmed that the IR780 were loaded on MXene.
Moreover, the absorption at 700 to 800 nanometers in Ti3C2@IR780 was stronger than that in IR780 and Ti3C2. The absorption peak at 596-centimeter inverse in infrared (IR) spectra of Ti3C2@IR780 corroborated the Ti-O-C bond in Ti3C2. The IR780 benzene ring’s alkene (C=C) and alkane (C-H) stretching vibration peaks were found at 1615, 1339, and 1252-centimeter inverse, demonstrating the assembly of IR780 and Ti3C2.
The IR780 PS is a well-known NIR-stimulated PTT and PDT cancer therapeutic agent that aggregated selectively in the mitochondria of a tumor cell without any ligand modification. The as-prepared Ti3C2@IR780 nanosheet concurrently generated heat and produced singlet oxygen at a wavelength of 808 nanometers. The synergic contribution of IR780 and Mxene in the designed nanoplatform simultaneously extended the IR780’s therapeutic window and fostered a high therapeutic index.
The results obtained from Ti3C2@IR780 under NIR light irradiation showed the efficiency of the as-prepared nanosheet in inhibiting tumor proliferation and ROS-mediated apoptosis in the mitochondrial pathway.
Additionally, the composite nanoplatform targeted the cancerous tissue for specific treatment and inhibited tumor growth through its phototherapeutic effects. The in vivo and in vitro experimental results revealed the excellent potential of Ti3C2@IR780 nanosheets in treating laryngeal cancer, thus hinting Ti3C2@IR780 a promising tool for laryngeal cancer treatment.
Conclusion
In summary, the researchers constructed an IR780-modified MXene multifunctional nanoplatform, which was dual-functional, NIR-sensitive, photodynamic, and photothermal for treating laryngeal cancer.
They found that under 808-nanometer laser irradiation, Ti3C2@IR780 achieved desirable anti-cancer effects, wherein loading IR780 onto MXene simultaneously extended it’s therapeutic window and enhanced the specificity and therapeutic efficiency in MXene nanoplatforms.
Results obtained from molecular biology studies revealed that, under light, the Ti3C2@IR780 nanosheet generated ROS and disrupted the mitochondrial function and mediated the apoptosis of the mitochondrial pathway in cancer cells. Furthermore, it inhibited the multiplication and migration of cancer cells.
With the help of in vivo experiments, the team confirmed that the Ti3C2@IR780 can persistently, efficiently, and preferably aggregate in the tumor tissues. Under the NIR light, the temperature of the tumor site reached 63.7 degrees celsius, which resulted in tumor supersession of up to 92%, with no recurrence.
Simultaneously, the Ti3C2@IR780 inhibited 88.1% of angiogenesis in tumor tissue. Thus, Ti3C2@IR780 proved to have the potential for laryngeal cancer treatment, which provided a new therapeutic approach to treating this cancer.
Reference
Lin, Y., Xu, S., Zhao, X., Chang, L., Hu, Y., Chen, Z., Mei, X et al (2022). Preparation of NIR-sensitive, photothermal and photodynamic multi-functional Mxene nanosheets for laryngeal cancer therapy by regulating mitochondrial apoptosis. Materials & Design. https://doi.org/10.1016/j.matdes.2022.110887
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