Advancements in tantalum based nanoparticles for integrated imaging and photothermal therapy in cancer management

Abstract

Tantalum-based nanoparticles (TaNPs) have emerged as promising tools in cancer management, owing to their unique properties that facilitate innovative imaging and photothermal therapy applications. This review provides a comprehensive overview of recent advancements in TaNPs, emphasizing their potential in oncology. Key features include excellent biocompatibility, efficient photothermal conversion, and the ability to integrate multifunctional capabilities, such as targeted drug delivery and enhanced imaging. Despite these advantages, challenges remain in establishing long-term biocompatibility, optimizing therapeutic efficacy through surface modifications, and advancing imaging techniques for real-time monitoring. Strategic approaches to address these challenges include surface modifications like PEGylation to improve biocompatibility, precise control over size and shape for effective photothermal therapy, and the development of biodegradable TaNPs for safe elimination from the body. Furthermore, integrating advanced imaging modalities-such as photoacoustic imaging, magnetic resonance imaging (MRI), and computed tomography (CT)-enable real-time tracking of TaNPs in vivo, which is crucial for clinical applications. Personalized medicine strategies that leverage biomarkers and genetic profiling also hold promise for tailoring TaNP-based therapies to individual patient profiles, thereby enhancing treatment efficacy and minimizing side effects. In conclusion, TaNPs represent a significant advancement in nanomedicine, poised to transform cancer treatment paradigms while expanding into various biomedical applications.

Fig. 1. TEM images and SAED pattern (inset) of dense Ta₂O₅ films at different magnifications (a) 40 000× and (b) 150 000× (Reproduced from ref. with permission from Springer Nature copyright [2024]).

Fig. 2. TEM images of porous Ta₂O₅ films prepared with addition of 5% organic template of copolymers PE6200 (a), PE6400 (c), PE6800 (e) and PE9400 (g) and 20% of PE6200 (b), PE6400 (d), PE6800 (f) and 15% of PE9400 (h); size distribution of the pores of Ta₂O₅ templated with 5% PE9400 (i) and 15% PE9400 (j). (Inset): typical SAED (selected area electron diffraction) pattern. The bar is 20 nm (ref. 43) (Reproduced from ref. with permission from Springer Nature copyright [2024]).

Fig. 3. Synthetic procedure of Ta₂O₅ films prepared by the sol–gel method using photo-irradiation (Reproduced from ref. with permission from Elsevier copyright [2024]).

Fig. 4. Cross-section of Ta₂O₅ thin film prepared by the sol–gel method using photo-irradiation (Reproduced from ref. with permission from Elsevier copyright [2024]).

Fig. 5. Preparation of sol–gel solution and the steps for powder producing and coating processes (Reproduced from ref. with permission from Springer Nature copyright [2024]).

Fig. 6. SEM images of Ta₂O₅-coated AZ91 Mg alloy (a) C₁, (b) C₂, and (c) C₃ (Reproduced from ref. with permission from Springer Nature copyright [2024]).

Fig. 7. SEM images of the powders prepared at different C/Ta molar ratios by SPS at 1500 °C for 5 min: (a) C/Ta = 3.75, (b) C/Ta = 4.00, (c) C/Ta = 4.25, (d) C/Ta = 4.50 (Reproduced from ref. with permission from Elsevier copyright [2024]).

Fig. 8. FESEM images of powders synthesized at the C/Ta molar ratio of 4.25 at different temperatures: (a) 1400 °C, (b) 1500 °C, (c) 1600 °C (Reproduced from ref. with permission from Elsevier copyright [2024]).

Fig. 9. TEM photographs of Ta-1 (a) and Ta-4 (b and c) (Reproduced from ref. with permission from Royal Society of Chemistry copyright [2024]).

Fig. 10. Displays transmission electron microscopy (TEM) images (a–g) depicting tantalum oxide nanoparticles at various pH levels: (a) pH 3, (b) pH 4, (c) pH 7, (d) pH 8, (e) pH 9, (f) pH 12, and (g) pH 13. Additionally, (h) presents the pH values of the reaction mixtures prior to hydrothermal treatment, as determined by NaOH concentration (Reproduced from ref. with permission from Royal Society of Chemistry copyright [2024]).

Fig. 11. TEM images of the nanoparticles yielded with different bases at different pH values. (a) pH 7 with KOH, (b) pH 7 with RbOH as the precursor base and (c) KOH and (d) RbOH as precursor bases both at pH 12 (Reproduced from ref. with permission from Royal Society of Chemistry copyright [2024]).

Fig. 12. (a–d). FE-SEM in cross-sectional view film morphologies of the prepared samples. (e) The film thicknesses obtained from both techniques (Reproduced from ref. with permission from Elsevier copyright [2024]).

Fig. 13. In vivo X-ray CT imaging. (a and b) Serial CT coronal views of a rat following injection of 1 mL of PEG-RITC-TaO_x solution (840 mg kg⁻¹) into the tail vein. (a) Heart and liver (coronal view cut along the yellow dotted line in (c)). (b) Spleen, kidney, and inferior vena cava (coronal view cut along the white dotted line in (c)). (c) 3D-renderings of in vivo CT images reveal the ventral (top) and lateral (bottom) sides of the heart and great vessels. The images were obtained immediately after injection (Reproduced from ref. with permission from American Chemical Society copyright [2024]).

Fig. 14. Sentinel lymph node mapping and resection. (a) In vivo CT volume-rendered (upper left) and maximum intensity projections (MIP) images (upper right and lower panels) of the sentinel lymph node of the rat were obtained 2 h after intradermal injection of 100 μL of PEG-RITCTaO_x solution (210 mg mL⁻¹) in both paws. The yellow circles and arrows indicate the locations of the lymph nodes. (b) White light photographs (upper panels) and fluorescence images (lower panels) of the rat injected intradermally with 100 μL of PEG-RITC-TaO_x solution in both paws. Lateral views of the rat 2 h after injection show highly intense red emission from the lymph node and injected part (left and middle). Arrows and circles indicate the putative axillary sentinel lymph nodes and injection point, respectively. Sentinel lymph nodes of the two rats dissected by bimodalimage-guided surgery (right) (Reproduced from ref. with permission from American Chemical Society copyright [2024]).

Fig. 15. (a) In vitro CT images and (b) CT contrasts of MnO_x/Ta₄C₃-SP composite nanosheet solutions and iopromide solutions at varied concentrations (0.1, 0.3, 0.6, 1.3, 2.5, 5.0, and 10 mg mL⁻¹ with respect to Ta and I, respectively). (c) Schematic of in vivo CT imaging by using MnO_x/Ta₄C₃-SP composite nanosheets as the contrast agents. (d) In vivo CT contrasts of tumor tissue before and after i.v. administration of MnO_x/Ta₄C₃-SP composite nanosheets. (e) In vivo 3D reconstruction CT images (left) and contrast images (right) of mice before and after i.v. administration of MnO_x/Ta₄C₃-SP composite nanosheets (20 mg kg⁻¹, 100 μL) for 2 h (Reproduced from ref. with permission from American Chemical Society copyright [2024]).

Fig. 16. CT coronal views of GI tract of the rat administered with Ta₂O₅ NPs (Reproduced from ref. with permission from Royal Society of Chemistry copyright [2024]).

Fig. 17. Characteristics of contrast agents and their signal attenuation profiles in various solutions. (A) Annotated microCT images of TaO_x-infused mammary glands (36 mg Ta per ml stock, also shown at lower magnification in (C)); pink lines outline the abdominal mammary glands, and blue arrows indicate filled branches of the ductal tree. (B and C) Tissue phantoms and mice were scanned using the same microCT imaging parameters. Top panels (tissue phantoms): each contrast agent was diluted from stock reagent (maximal concentration) in PBS or 70% ethanol (EtOH) at the indicated concentrations (mg of metal per ml). Linear fitting of signal attenuation as a function of the metal concentration in each solution. Bottom panels: representative single-slice micro CT images of the lower body of animals captured immediately after the last ID injection of each indicated solution: Omnipaque (300 mg I per ml stock, 90 mg I per ml in EtOH), MVivo Au (200 mg Au per ml stock, 60 mg Au per ml in EtOH), TaO_x (36 mg Ta per ml stock, 10.8 mg Ta per ml in EtOH), Fenestra VC (50 mg I per ml stock, 15 mg I per ml in EtOH), MVivo BIS (150 mg Bis per ml stock, 45 mg Bis per ml in EtOH). Arrows indicate areas where leaked contrast agent accumulates on the fascia boundary. Scale bar is 10 mm in images at different magnifications (Reproduced from ref. with permission from Springer Nature copyright [2024]).

Fig. 18. Active and passive uptake of nanoparticles. NPs, nanoparticles; EPR, enhanced permeability retention (Reproduced from ref. with permission from Portland Press copyright [2024]).

Fig. 19. The enhanced permeability and retention (EPR) effect (Reproduced from ref. with permission from Portland Press copyright [2024]).

Fig. 20. Schematic representation highlighting (A) the conceptual structure of an ADC and a multifunctional antibody conjugated nanoparticle and (B) internalisation, breakdown, and drug release within the cell. The tumour-specific ligand of the ADC or nanoparticle interacts with and binds to the cell surface expressed antigen. Upon binding, the antigen–protein complex becomes internalised via receptor mediated endocytosis. The nanoparticle or ADC linker is degraded within the endo-lysosomal system, resulting in drug release within the cell (Reproduced from ref. with permission from Portland Press copyright [2024]).

Fig. 21. The mechanism of photodynamic triggering immunotherapy. Photodynamic therapy tumor cell apoptosis and necrosis, releasing tumor antigens and injury-related molecular patterns, including CRT, HSPs, and HMGB1. Activated CD₄⁺ and CD₈⁺ T cells are gathered in the lymph nodes and kill the tumor cells by inherent immunity and adaptive immunity. TLR-2/4: toll-like receptor on the surface of the mononuclear macrophages; MHC I/II: Major histocompatibility class I/II (Reproduced from ref. with permission from Wiley online Library copyright [2024]).

Fig. 22. Illustration of theranostic functions of MnO_x/Ta4C₃-SP composite nanosheets, i.e., MR/CT/PA imaging-guided efficient PTT ablation of cancer.

Fig. 23. Photothermal ablation of HeLa cancer cells in vitro. (a) Fluorescence microscopy images of HeLa cells treated differently as indicated. Scale bar is 1 mm. (b) Cell viability of HeLa cells after incubation with PEGylated TaNPs as well as laser irradiation (808 nm, 4 W cm⁻²) for 10 min, p < 0.001 (***) (Reproduced from ref. with permission from Wiley online Library copyright [2024]).

Fig. 24. (A) Thermal images and (B) photothermal curves of TaN-PVP dispersions at varying concentrations (100–300 μg mL⁻¹), with ultrapure water serving as the control. (C) Photothermal response of a 300 μg mL⁻¹ TaN-PVP solution under 1064 nm laser irradiation, followed by cooling. (D) Cooling time plotted against the negative natural logarithmF of the temperature driving force. (E) Evaluation of photothermal stability through five consecutive laser on/off cycles. (F) PA signal intensity and images of TaN-PVP dispersions at specified concentrations (Reproduced from ref. with permission from MDPI copyright [2024]).

Fig. 25. Confocal images of cells on VT, VT200, and VT400 before ((a–c) respectively) and after ((d–f) respectively) irradiation (Reproduced from ref. with permission from MDPI copyright [2024]).