Injectable and Temperature-Sensitive Titanium Carbide-Loaded Hydrogel System for Photothermal Therapy of Breast Cancer

Abstract

Recently, organic-inorganic hybrid materials have gained much attention as effective photothermal agents for cancer treatment. In this study, Pluronic F127 hydrogel-coated titanium carbide (Ti₃C₂) nanoparticles were utilized as an injectable photothermal agent. The advantages of these nanoparticles are their green synthesis and excellent photothermal efficiency. In this system, lasers were mainly used to irradiate Ti₃C₂ nanoparticles to produce a constant high temperature, which damaged cancer cells. The nanoparticles were found to be stable during storage at low temperatures for at least 2 weeks. The Ti₃C₂ nanoparticles exhibited a shuttle-shaped structure, and the hydrogels presented a loosely meshed structure. In addition, Ti₃C₂ nanoparticles did not affect the reversible temperature sensitivity of the gel, and the hydrogel did not affect the photothermal properties of Ti₃C₂ nanoparticles. The in vitro and in vivo results show that this hydrogel system can effectively inhibit tumor growth upon exposure to near-infrared irradiation with excellent biocompatibility and biosafety. The photothermal agent-embedded hydrogel is a promising photothermal therapeutic strategy for cancer treatment by enhancing the retention in vivo and elevating the local temperature in tumors.

Keywords: Ti3C2 nanoparticles; anti-cancer; photothermal therapy; pluronic F127 hydrogel; thermosensitive.

FIGURE 1

Schematic illustration of the fabrication of the injectable hydrogel system with excellent photo–heat transition capacity. This system was fabricated using a one-step synthesis method. Ti₃C₂ nanoparticles and thermosensitive Pluronic F127 were mixed to prepare the photothermal agent-embedded hydrogel system. The system can form in situ gel in tumor tissue through sol–gel transition and prolong the retention of Ti₃C₂ nanoparticles. Using near-infrared laser irradiation, repeated treatments can be achieved with a single injection.

FIGURE 2

Preparation and characterization of Ti₃C₂ nanoparticles and Ti₃C₂-Gel. Transmission electron microscopy image of (A) Ti₃C₂ MXene solution (scale bar: 200 nm), (B) Ti₃C₂ nanoparticles (scale bar: 100 nm), and (C) Ti₃C₂-Gel (scale bar: 200 nm). (D) Scanning electron microscopy image of Pluronic F-127 gel (scale bar: 1 mm). (E) Energy-dispersive X-ray image of Ti₃C₂-Gel (scale bar: 50 nm). (F) Particle sizes of Ti₃C₂ nanoparticles and Ti₃C₂-Gel. (G) Zeta potentials of the different preparations. (H) Stability of Ti₃C₂ and Ti₃C₂-Gel sizes.

FIGURE 3

Assessment of photothermal properties. (A) Morphology of Pluronic F127 gel and Ti₃C₂-gel at 4°C and 37°C. (B,C) Phase transition temperature of Pluronic F127 gel and Ti₃C₂-Gel (concentration of Ti₃C₂ was 50 μg/ml). (D,E) Rheological properties of Pluronic F127 and Ti₃C₂-gel (concentration of Pluronic F127 was 20%, and that of Ti₃C₂ was 50 μg/ml).

FIGURE 4

In vitro photothermal performance. (A,B) Temperature diagram of Ti₃C₂ nanoparticles and Ti₃C₂-Gel under 808-nm irradiation (1 W/cm²). (C,D) Heating curve of different concentrations of Ti₃C₂ nanoparticles and Ti₃C₂-Gel under 808-nm irradiation (1 W/cm²). (E,F) Heating curves of Ti₃C₂ nanoparticles and Ti₃C₂-Gel treated with repeated 808-nm irradiation (1 W/cm²). (G) Viabilities of 4T1 cells incubated with different concentrations of Ti₃C₂ nanoparticles in DMEM media for 12 h. (H) Cytotoxicity of Ti₃C₂ nanoparticles against 4T1 cells exposed to the 808-nm NIR laser (1 W/cm²) for 1 min (n = 4/group).

FIGURE 5

In vivo antitumor performance. (A) Digital images of tumors of mice after treatment. (B) Thermal images of mice irradiated with an 808-nm laser. (C–E) Temperature in tumor-bearing mice recorded by a thermal imager under the 808-nm laser. (F) Growth curves of tumors in all mice after treatment. n = 5/group, mean ± SD, **p < 0.01. (G) Average body weight of mice in different groups.

FIGURE 6

In vivo safety evaluation. (A–C) Blood biochemistry analysis (including indicators of liver and kidney function) of mice after various treatments. n = 3/group, mean ± SD. (D) Hematoxylin and eosin staining and TUNEL staining of tumor sections from different treatment groups.