A biodegradable "one-for-all" nanoparticle for multimodality imaging and enhanced photothermal treatment of breast cancer

Abstract

Silver sulfide nanoparticles (Ag2S-NP) have been proposed for various optical-based biomedical applications, such as near-infrared fluorescence (NIRF) imaging, photoacoustics (PA) and photothermal therapy (PTT). However, their absorbance is relatively low in the NIR window used in these applications, and previous formulations were synthesized using toxic precursors under harsh conditions and have clearance issues due to their large size. Herein, we synthesized sub-5 nm Ag2S-NP and encapsulated them in biodegradable, polymeric nanoparticles (AgPCPP). All syntheses were conducted using biocompatible reagents in the aqueous phase and under ambient conditions. We found that the encapsulation of Ag2S-NP in polymeric nanospheres greatly increases their NIR absorbance, resulting in enhanced optical imaging and photothermal heating effects. We therefore found that AgPCPP have potent contrast properties for PA and NIRF imaging, as well as for computed tomography (CT). We demonstrated the applicability of AgPCPP nanoparticles as a multimodal imaging probe that readily improves the conspicuity of breast tumors in vivo. PTT was performed using AgPCPP with NIR laser irradiation, which led to significant reduction in breast tumor growth and prolonged survival compared to free Ag2S-NP. Lastly, we observed a gradual decrease in AgPCPP retention in tissues over time with no signs of acute toxicity, thus providing strong evidence of safety and biodegradability. Therefore, AgPCPP may serve as a "one-for-all" theranostic agent that degrades into small components for excretion once the diagnostic and therapeutic tasks are fulfilled, thus providing good prospects for translation to clinical use. TOC graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=119 SRC="FIGDIR/small/568885v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@e6be5dorg.highwire.dtl.DTLVardef@dbce2eorg.highwire.dtl.DTLVardef@bd5360org.highwire.dtl.DTLVardef@1acf01d_HPS_FORMAT_FIGEXP M_FIG C_FIG