Triphase interface synthesis of plasmonic gold bellflowers as near-infrared light mediated acoustic and thermal theranostics

Abstract

We present a novel gold bellflower (GBF) platform with multiple-branched petals, prepared by a liquid-liquid-gas triphase interface system, for photoacoustic imaging (PAI)-guided photothermal therapy (PTT). Upon near-infrared (NIR) laser irradiation, the GBFs, with strong NIR absorption, showed very strong PA response and an ultrahigh photothermal conversion efficiency (η, ∼74%) among the reported photothermal conversion agents. The excellent performance in PAI and PTT is mainly attributed to the unique features of the GBFs: (i) multiple-branched petals with an enhanced local electromagnetic field, (ii) long narrow gaps between adjacent petals that induce a strong plasmonic coupling effect, and (iii) a bell-shaped nanostructure that can effectively amplify the acoustic signals during the acoustic propagation. Besides the notable PTT and an excellent PAI effect, the NIR-absorbing GBFs may also find applications in NIR light-triggered drug delivery, catalysis, surface enhanced Raman scattering, stealth, antireflection, IR sensors, telecommunications, and the like.

Figure 1

Characterization of plasmonic GBFs. TEM (a, c) and SEM (b, d) images of GBFs. (e) Vials containing the GBFs prepared at different time points (i, 0.5; ii, 1; iii, 2; iv, 5; v, 60; vi, 90 min) and (f) the corresponding UV–vis–NIR absorbance spectra. Scale bar, 100 nm.

Figure 2

TEM images of the growth patterns of GBFs in the liquid–liquid–gas triphase interface system. A redox reaction occurs along the liquid–liquid–gas triphase interface of the outward flange bubbles (a–d); a redox reaction occurs along the liquid–liquid–gas triphase interface of the concave bubbles (e–h). Scale bar, 100 nm.

Figure 3

Photothermal conversion and photoacoustic properties of GBFs. NIR laser-induced heat generation of aqueous solution of GBFs (a) with the same laser power density of 1 W/cm² and different ODs at 808 nm and (b) with the same OD_808 nm value of 0.5 and irradiated at different laser power densities. (c) Temperature elevation of the aqueous solutions of GNRs and GBFs exposed to an 808 nm laser (OD_808 nm = 1, 1 W/cm²) as a function of irradiation time. The irradiation lasted for 5 min, and then the laser was turned off. Pure water was used as a negative control. (d) PA signals of GBFs, GNRs, and gold nanostars (GNSs) as a function of OD. (e) PA images of GBFs at different OD_808 nm values.

Figure 4

In vitro cell experiments. (a) Calcein AM and PI costaining of the 4T1 cells without and with incubation with GBFs (100 μg/mL) for 4 h before exposure to an 808 nm laser at different power densities. (b) Relative viabilities of the 4T1, Hela, SCC7, and CHO cells after incubation with GBFs for 24 h. (c) Relative viabilities of the 4T1 cells after GBF-induced photothermal therapy at different laser power densities. Error bars were based on the standard deviations of five parallel samples.

Figure 5

In vivo photothermal and PA imaging. (a) Thermal images of 4T1 tumor mice with GBF injection and exposure to an 808 nm laser. As a control, thermal images of mice with PBS injection and exposure to an 808 nm laser at the power density of 1 W/cm² were taken. (b) 2D ultrasonic (US) and PA images and 3D PA images of tumor tissues pre- and post-injection of GBFs (white arrow, needle; red arrow, GBFs). (c) Heat curves of 4T1 tumors upon laser irradiation as a function of irradiation time. (d) Time-lapse PA signal change followed by intratumoral injection of GBFs. (e) PA spectra of GBFs after injection.

Figure 6

In vivo PTT. (a) Relative 4T1 tumor volume after various treatments. Tumor volumes were normalized to their initial sizes. Error bar, standard deviation of 5–7 mice. *P < 0.01. (b) Survival curves of the 4T1 tumor mice after various treatments. GBF-injected mice after PTT treatment showed complete tumor regression and 100% survival over 40 days. (c) Photographs of the 4T1 tumor mice on different days after the GBF treatment. (d) Hematoxylin and eosin (HE) staining of tumor sections collected from different treatment groups of mice at day 1.