Abstract
Targeted theranostic platform that integrates multi-modal imaging and therapeutic function is emerging as a promising strategy for earlier detection and precise treatment of cancer. Herein, we designed targeted gold-nanoshelled poly (lactic-co-glycolic acid) (PLGA) magnetic hybrid nanoparticles carrying anti-human epidermal growth factor receptor 2 (Her2) antibodies (Her2-GPH NPs) for dual-modal ultrasound (US)/magnetic resonance (MR) imaging and photothermal therapy of breast cancer. The agent was fabricated by coating gold nanoshell around PLGA nanoparticles co-loaded with perfluorooctyl bromide (PFOB) and superparamagnetic iron oxide nanoparticles (SPIOs), followed by conjugating with anti-Her2 antibodies. Cell-targeting studies demonstrated receptor-mediated specific binding of the agent to Her2-positive human breast cancer SKBR3 cells, and its binding rate was significantly higher than that of Her2-negative cells (P < 0.001). In vitro, the agent had capabilities for contrast-enhanced US imaging as well as T2-weighted MR imaging with a relatively high relaxivity (r2 = 441.47 mM−1 s−1). Furthermore, the Her2 functionalization of the agent prominently enhanced the US/MR molecular imaging effect of targeted cells by cell-specific binding. Live/dead cell assay and targeted photothermal cytotoxicity experiments confirmed that Her2-GPH NPs could serve as effective photoabsorbers to specifically induce SKBR3 cell death upon near-infrared laser irradiation. In summary, Her2-GPH NPs were demonstrated to be novel targeted theranostic agents with great potential to facilitate early non-invasive diagnosis and adjuvant therapy of breast cancer.
Highlights
Breast cancer is the leading cause of cancer-related deaths among women worldwide [1]
Characterizations Perfluorooctyl bromide (PFOB)/superparamagnetic iron oxide nanoparticles (SPIOs)@Poly lactic-co-glycolic acid (PLGA) Gold-nanoshelled magnetic hybrid nanoparticles (NPs) were fabricated via the oil/ water emulsion solvent evaporation process
human epidermal growth factor receptor 2 (Her2)-GPH NPs were prepared by linking anti-Her2 antibodies to PFOB/SPIOs@PLGA@Au NPs via SH-PEG-COOH
Summary
Breast cancer is the leading cause of cancer-related deaths among women worldwide [1]. The key to effectively reduce death from breast cancer is early and accurate diagnosis [2]. Despite advances in recent decades, current diagnostic and therapeutic strategies still have limitations in the early detection and precise treatment of breast cancer [3]. Theranostics, which involves the combination of diagnostic and therapeutic approaches within one platform, is expected to play a significant role in advancing personalized medicine [4]. Theranostic agents integrate molecular imaging and therapeutic function into a single nanoparticle, given the potential to simultaneously monitor and treat breast cancer at the cellular or molecular levels [5]. Ultrasound (US) and magnetic resonance imaging (MRI) are the two commonly used methods for diagnosis and staging of breast cancer [6]. US imaging shows advantages of high safety, real-time measurement and readily availability, and
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