Polydopamine coated multifunctional lanthanide theranostic agent for vascular malformation and tumor vessel imaging beyond 1500 nm and imaging-guided photothermal therapy

Abstract

The optical imaging guided tumor vessels and vascular malformation visualization by using the second near infrared emission beyond 1500 nm (NIR-II) is emerged as the next generation fluorescence imaging technique for early tumor diagnosis and identification of tumor-associated vascular features. On the other hand, developing theranostic probes for NIR-II imaging guided photothermal therapy (PTT) is of great significance, which is rarely explored. Herein, a high performance theranostic nanoplatform based on the core-shell structured NaLuF₄ nanorods@polydopamine (denoted as NRs@PDA) by integrating the new advanced NIR-II imaging beyond 1500 nm with PTT function was developed for tumor-associated vascular malformation visualization and imaging-guided PTT. Methods: In this work, the hydrophilic NaLuF₄ NRs@PDA therapeutic probe was synthesized by using a reverse microemulsion method. The crystal phase, morphology, emission spectra and photothermal performance of the synthesized samples were systematically characterized. The NIR-II optical imaging and photothermal properties were investigated by in vitro and in vivo experiments. Results: The NaLuF₄ NRs@PDA therapeutic probe possessed efficient NIR-II emission centered at 1525 nm with high quantum yield (QY), good photo-stability and high biocompatibility. In vivo NIR-IIb imaging based on the designed probe can clearly visualize the whole-body vessel and brain vessel with high spatial resolution, especially tumor-associated vessels. In addition, in vitro and in vivo experiments also demonstrated that the designed NaLuF₄ NRs@PDA probe possessed efficient photothermal conversion efficiency (40.18%) for PTT ablation of tumor. Conclusion: With the excellent NIR-II imaging ability and PTT of tumor, the designed theranostic nanoplatform successfully realize the simultaneous tumor vessel diagnosis and tumor therapy, which may provide the opportunity of designing new theranostic bioprobes with combination of the NIR-II optical imaging technique and PTT function for tumor diagnosis and therapy.

Keywords: Lanthanide nanorods; photothermal therapy; theranostic nanoplatform; tumor angiography.

Scheme 1

Schematic illustration of designing NRs@PDA multifunctional theranostic bioprobes for NIR-II imaging-guided tumor vessel tracking and PTT of tumor.

Figure 1

TEM images of the NaLuF₄: Gd/Yb/Er NRs: (A) low magnification and (B) high magnification. (C) TEM image of NRs@PDA nanocomposites. (D) HR-TEM image of a single NaLuF₄ NR. (E) STEM image of NaLuF₄ NRs@PDA. (F) Simplified energy level diagram revealing the energy transfer between Yb³⁺ and Er³⁺. (G) XRD patterns of NaLuF₄ NRs and NRs@PDA. (H) UC and DC luminescence spectra of NaLuF₄ NRs and NRs@PDA.

Figure 2

NIR-II imaging guided tumor vessel tracking and whole-body vessel imaging: (A) LLC tumor-bearing mouse. (B) Normal mouse. (C) and (E) The corresponding zoom-in images of the chosen vessels taken from the rectangle in (A) and (B), respectively. (D) Cross-sectional NIR-II intensity profiles along a green line in tumor-bearing mouse. (F) Cross-sectional NIR-II intensity profiles along a blue line in normal mouse. All scale bars are 10 mm.

Figure 3

(A) Schematic illustration of non-invasive NIR-II imaging-guided tumor vessel diagnosis. (B) A digital photograph of the tumor-bearing mouse (HCT-116). (C) Bright field image and (D) NIR-II imaging of tumor. The time course of low-magnification (E) and high-magnification (F) tumor vascular imaging. (G) The zoom-in image of the chosen vessels marked by cyan circle in (F). (H) Cross-sectional intensity profiles along the colour lines marked in (G). The scale bar is 2 mm.

Figure 4

(A) Time-dependent non-invasive in vivo brain vessel imaging; 1, 2 and 3 marked in (A) present the inferior cerebral vein, superior sagittal sinus and transverse sinus depths, respectively. (B) A cerebral vascular image. (C) and (D) The corresponding zoom-in images of the chosen vessels. (E) and (F) Cross-sectional intensity profiles (black curves), Gaussian function fitting lines (colorized curves) and FWHM values measured along the colorized lines from the images of (C) and (D). Scale bars: 2 mm.

Figure 5

(A) The UV-vis-NIR absorption spectrum of the NRs@PDA solution and the corresponding photograph (the inset). (B) Temperature variation curves of NRs@PDA solutions with different concentrations recorded under 808 nm laser irradiation. (C) Temperature variation curves of NRs@PDA solutions under irradiation with different powers of 808 nm laser. (D) Temperature change of NRs@PDA solutions under four heating/cooling cycles. (E) The photothermal response of the NRs@PDA solution with laser and then the laser was ceased for naturally cooling. (F) Cooling time versus negative natural logarithm of driving force temperature obtained from the cooling stage of (E).

Figure 6

(A) In vivo photothermal imaging of mice subcutaneous injection with PBS and NRs@PDA solution under the irradiation of 808 nm laser. (B) The photographs of dissected tumor from the different groups of tumor mice at the end of PTT time. (C) Relative tumor volume after treatment with PBS, NRs@PDA, Laser (control) and NRs@PDA + 808 nm Laser irradiation.