Silica-Capped and Gold-Decorated Silica Nanoparticles for Enhancing Effect of Gold Nanoparticle-Based Photothermal Therapy

Abstract

Background: Various methods based on gold nanoparticles (AuNPs) have been applied to enhance the photothermal effect. Among these methods, combining gold nanoparticles and stem cells has been suggested as a new technique for elevating the efficiency of photothermal therapy (PT) in terms of enhancing tumor targeting effect. However, to elicit the efficiency of PT using gold nanoparticles and stem cells, delivering large amounts of AuNPs into stem cells without loss should be considered.

Methods: AuNPs, AuNPs-decorated silica nanoparticles, and silica-capped and AuNPs-decorated silica nanoparticles (SGSs) were synthesized and used to treat human mesenchymal stem cells (hMSCs). After evaluating physical properties of each nanoparticle, the concentration of each nanoparticle was estimated based on its cytotoxicity to hMSCs. The amount of AuNPs loss from each nanoparticle by exogenous physical stress was evaluated after exposing particles to a gentle shaking. After these experiments, in vitro and in vivo photothermal effects were then evaluated.

Results: SGS showed no cytotoxicity when it was used to treat hMSCs at concentration up to 20 μg/mL. After intravenous injection to tumor-bearing mice, SGS-laden hMSCs group showed significantly higher heat generation than other groups following laser irradiation. Furthermore, in vivo photothermal effect in the hMSC-SGS group was significantly enhanced than those in other groups in terms of tumor volume decrement and histological outcome.

Conclusion: Our results suggest that additional silica layer in SGSs could protect AuNPs from physical stress induced AuNPs loss. The strategy applied in SGS may offer a prospective method to improve PT.

Keywords: Gold nanoparticles; Photothermal therapy; Silica capping.

Fig. 1

Schematic illustration of anti-tumor treatment using silica (Si)-capped gold (Au) decorated Si nanoparticles (SGSs). Si nanoparticles were applied to protect Au nanoparticles attached on the surface of Si nanoparticles from physical stress and Si degradation. Based on the improved long-term circulation and high photothermal effect induced by combining SGSs and human mesenchymal stem cells (hMSCs), therapeutic photothermal effect was significantly enhanced when compared to that of conventional photothermal therapy (PT) using Au nanoparticles (AuNPs)

Fig. 2

Preparation and physical property of AuNPs-decorated Si nanoparticle (GS) and SGS. A. Procedure used for preparing GS and SGS. B TEM images of AuNP, GS, and SGS at different magnifications. C Normalized absorbance of AuNP, GS, and SGS. D SEM images of GS and SGS at different magnifications. E Amount of gold and ratio between gold and Si in each particle. F Relative amount of gold detached from Si nanoparticles under physical stress (n = 5, **p < 0.001 versus GS group). G Temperature increment during 660 nm laser irradiation for 2 min according to concentration difference of each nanoparticle (n = 4, *p < 0.05 versus all other groups)

Fig. 3

Cytotoxic effect of AuNPs, GSs, and SGSs at different concentrations for 24 h culturing with hMSCs. A–C. Expression levels of pro-apoptotic factor, p53, according to different concentrations of each nanoparticle (n = 4, * p < 0.05 versus all other groups). D Cell viability of hMSCs evaluated by live and dead (fluorescein diacetate (FDA)/ethidium bromide (EB)) assay according to the different concentrations of each nanoparticle. Green (FDA-positive signal) indicates live cells and red (EB-positive signal) indicates dead cells (white arrows). Scale bars indicate 100 μm

Fig. 4

In vivo therapeutic effect of SGSs-laden hMSCs on tumor bearing mouse model after intravenous injection. A,B Temperature increment and representative real-time infrared thermal images of tumor sites at three days after hMSCs or various nanoparticles-laden hMSCs injections with laser irradiation up to 2 min. C Changes in tumor volume for 7 days after various treatments (n = 4, * p < 0.05 versus all other groups). D Representative images of tumors at days 3 and 7 after various treatments. E Representative hematoxylin and eosin staining images of tumor site at 7 days after various treatments