In-situ TiO2-x decoration of titanium carbide MXene for photo/sono-responsive antitumor theranostics

Abstract

Background Sonodynamic therapy (SDT) has emerged as a noninvasive therapeutic modality that involves sonosensitizers and low-intensity ultrasound. However, owing to the rapid recombination of charge carriers, most of the sonosensitizers triggered poor reactive oxygen species (ROS) generation, resulting in unsatisfactory sonodynamic therapeutic effects. Results Herein, a photo/sono-responsive nanoplatform was developed through the in-situ systhesis of TiO2-x on the surface of two-dimensional MXene (titanium carbide, Ti3C2) for photoacoustic/photothermal bimodal imaging-guided near-infrared II (NIR-II) photothermal enhanced SDT of tumor. Because of several oxygen vacancies and smaller size (~ 10 nm), the in-situ formed TiO2-x nanoparticles possessed narrow band gap (2.65 eV) and high surface area, and thus served as a charge trap to restrict charge recombination under ultrasound (US) activation, resulting in enhanced sonodynamic ROS generation. Moreover, Ti3C2 nanosheets induced extensive localized hyperthermia relieves tumor hypoxia by accelerating intratumoral blood flow and tumor oxygenation, and thus further strengthened the efficacy of SDT. Upon US/NIR-II laser dual-stimuli, Ti3C2@TiO2-x nanoplatform triggered substantial cellular killing in vitro and complete tumor eradication in vivo, without any tumor recurrence and systemic toxicity. Conclusion Our work presents the promising design of photo/sono-responsive nanoplatform for cancer nanotheranostics. Graphical Abstract

Two-Dimensional MXene-Originated In Situ Nanosonosensitizer Generation for Augmented and Synergistic Sonodynamic Tumor Nanotherapy

“…In response to H 2 O 2 overproduction, the sonosensitizer TiO 2 is in situ generated in Ti 3 C 2 MXene to form TiO 2 /Ti 3 C 2 nanosheets. Due to the excellent electrical conductivity of the carbon matrix, , the separation of electrons (e – ) and holes (h + ) is promoted under US irradiation. Simultaneously, the cavitation effect of US could enhance the chemodynamic process.…”

“…Owing to the promising biomedical characteristics, 2D MXenes (titanium carbide, Ti 3 C 2 ) have been utilized as delivery platforms to load different types of sonosensitizer for enhancing the synergistic effect of the photothermal-sonodynamic therapeutic. 24,25 To our knowledge, the utilization of the physicochemical properties of Ti 3 C 2 to in situ generate sonosensitizers for SDT has not been achieved.…”

“…Thus, how to increase the accumulation of sonosensitizers in the tumor site without affecting the concentration in the blood to avoid dose-dependent toxicity to healthy tissues/organs is an urgent problem that needs to be solved. Owing to the promising biomedical characteristics, 2D MXenes (titanium carbide, Ti 3 C 2 ) have been utilized as delivery platforms to load different types of sonosensitizer for enhancing the synergistic effect of the photothermal-sonodynamic therapeutic. , To our knowledge, the utilization of the physicochemical properties of Ti 3 C 2 to in situ generate sonosensitizers for SDT has not been achieved.…”

Facile synthesis of near-infrared responsive on-demand oxygen releasing nanoplatform for precise MRI-guided theranostics of hypoxia-induced tumor chemoresistance and metastasis in triple negative breast cancer

“…Versus PTX and NIR-triggered PPSiI, O 2 -PPSiI under NIR laser irradiation showed more high-efficiency ROS and 1 O 2 generation in solution and MDA-MB-231 cells (Additional file 1 : Fig. S15), indicating an important role of O 2 release in the production of 1 O 2 and ROS [ 50 , 51 ]. Subsequently, the in vivo synergistic antitumor effect of the NIR-triggered O 2 -PPSiI nanosystem was further investigated with MDA-MB-231-bearing nude mice.…”

Roles of MXenes in biomedical applications: recent developments and prospects

“…Compared to the application of MXene alone in one area of treatment or diagnosis, researchers are more interested in developing its effective synergistic therapeutic effects with multiple treatment modalities. Combining PTT and PDT with other therapeutic diagnostic modalities synergistically can often produce unexpected results, such as combining PTT with PDT [ 165 ], PTT with SDT [ 166 ] or PTT with conventional chemotherapy and PDT or PTT with drug delivery [ 167 ]. Qun et al found that the synergistic effect of Mo 2 C-mediated PDT/PTT (induction of apoptosis) was significantly better than that of PDT or PTT alone by using the ROS buster NaN 3 to eradicate ROSs and using Mo 2 C-mediated phototherapy in an ice bath to eliminate the effects of PDT and PTT [ 157 ].…”