Gold nanoshelled liquid perfluorocarbon magnetic nanocapsules: a nanotheranostic platform for bimodal ultrasound/magnetic resonance imaging guided photothermal tumor ablation

Abstract

Imaging guided ablation therapy has been applied in both biomedical research and clinical trials and turned out to be one of the most promising approaches for cancer treatment. Herein, the multifunctional nanocapsules were fabricated through loading perfluorooctylbromide (PFOB) and superparamagnetic iron oxide nanoparticles (SPIOs) into poly(lactic acid) (PLA) nanocapsules (NCs), followed by the formation of PEGylated gold nanoshell on the surface. The resulting multi-component NCs were proved to be able to act as nanotheranostic agent to achieve successful bimodal ultrasound (US)/magnetic resonance imaging (MRI) guided photothermal ablation in human tumor xenograft models non-invasively. Such a single theranostic agent with the combination of real-time US and high-resolution MR imaging would be of great value to offer more comprehensive diagnostic information and dynamics of disease progression for the accurate location of therapeutic focusing spot in the targeted tumor tissue, showing great potential as an effective nanoplatform for contrast imaging guided photothermal therapy.

Keywords: Bimodal imaging; Gold nanoshell; Liquid perfluorocarbon nanocapules; Photothermal therapy.; Superparamagnetic iron oxide nanoparticles.

Fig 1

(A) Schematic illustration of the fabrication procedure of PGS-SP NCs; (B) The biomodal US/MRI guided tumor PTT process using the nanotheranostic agent.

Fig 2

(A, B) SEM images of the SP nanocapsules; (C) TEM images of SP NCs; (D) EDS spectrum comparison of SP NCs and PGS-SP NCs; (E) UV-vis spectra of the agent at different stages of fabrication process.

Fig 3

(A, B) SEM images of the PGS-SP nanocapsules; (C) TEM images of the agent; (D) Size distribution of the theranostic agent.

Fig 4

(A) Contrast enhanced US imaging at PIHI mode in the latex tube without and with the nanocapsule suspension; (B) The water proton transvers relaxation rate (T₂^-1) of PGS-SP NCs measured by a 0.47 T minispec analyzer as a function of Fe concentration; (C) in vitro T₂-weighted MR contrast images of the agent at different concentrations (TE = 60 ms; Fe concentration of sample 0~5: 0, 4.97, 9.93, 19.9, 39.7, 9.93 μM) under a 7 T MRI instrument; (D) temperature increase of PGS-SP NC suspension at different concentrastions under NIR laser irradiation (The thermometer probe was carefully placed in the top of the suspension for temperature monitoring to avoid the direct irradiation of NIR laser, which could dramatically affect the measurement.).

Fig 5

(A) Cell viabilities of HUVECs at different dosages of the agent (0, 0.01, 0.05, 0.1, 0.2, 0.5 mg mL^-1, data expressed as mean ± s.d.); (B) Cell viabilities of HeLa of PGS-SP NCs at different dosages (0, 0.005, 0.01, 0.025, 0.05, 0.1 mg mL^-1) with or without NIR laser irradiation (808 nm, 6.67 W cm^-2, 6 min, data expressed as mean ± s.d..); (C) Contrast enhanced US imaging at PIHI mode in rabbit kidney before and after intravenously injection of 0.1 mL kg^-1 40 mg mL^-1 of the agent (MI = 0.70).

Fig 6

(A) Contrast-enhanced ultrasonograms before, during and after the intratumoral injection of the agent (0.2 mL, 2 mg mL^-1) into the mice for visualization of the agent distribution to guide the following therapy (tumors highlighted by T); (B) T₂-weighted MR images of the tumors at different time points after intravenously injection of the agent (0.15 mL, 2 mg mL^-1) for visualization of tumor areas to guide the following photothermal ablation (tumors are highlighted in the red circles); (C) MR intensity changing profile of the tumors from tumor-bearing mice at different time points post intravenous administration of the nanocapsules.

Fig 7

(A) Therapeutic effectiveness expressed as tumor growth rate in each group after one-time treatment in nude mouse xenograft models (data expressed as mean ± s.d., n = 8); (B) Body weight change of mice in different groups after the treatment (data expressed mean ± s.d., n = 8); (C) Photographs of representative mice of the four different groups taken pre- and post-treatment, showing the significant therapeutic efficacy of agent+laser group compared to the other groups.