Abstract
Gold nanorods are effective photothermal agents in diagnosis and treatment of cancer due to their specific near-infrared laser absorption. However, tumor photothermal therapy by nanorods alone is lack of targeting. Here, we described a novel nanocomplex made up of gold nanorods, porphyrin, and trastuzumab, called TGNs and investigated the TGN-mediated photothermal therapy as a potential alternative treatment of targeting HER2-positive breast cancers. By conjugating trastuzumab and porphyrin to the surface of gold nanorods, we have increased the targeting specificity and amplified the detecting effectiveness at the same time. TGN-mediated photothermal ablation by near-infrared laser led to a selective destruction of HER2-positive cancer cells and significantly inhibited tumor growth in mouse models bearing HER2 over-expressed breast cancer xenograft with less toxicity. Moreover, TGNs provided better therapeutic efficacy in comparison with the conventional molecule targeted therapy. Our current data suggest a highly promising future of TGNs for its therapeutic application in trastuzumab-resistant breast cancers.
Highlights
Novel complex using gold nanorods (GNRs) coated with porphyrin as well as anti-HER2 antibody called GNRs-porphyrin-trastuzumab complexes (TGNs) and investigated the efficiency of this complex in targeting and photothermally ablating of HER2-positive breast cancer in vitro and vivo
In order to observe the morphological characteristics of TGNs, transmission electron microscopy (TEM) was conducted to compare TGNs with GNRs and GNRs-porphyrin (Fig. 1b)
No obvious change can be seen in GNRs-porphyrin compared with cetyltrime thylammonium bromide (CTAB)-coated GNRs
Summary
Novel complex using gold nanorods (GNRs) coated with porphyrin as well as anti-HER2 antibody (trastuzumab) called GNRs-porphyrin-trastuzumab complexes (TGNs) and investigated the efficiency of this complex in targeting and photothermally ablating of HER2-positive breast cancer in vitro and vivo. When changing the nanorods aspect ratio, the plasmon resonance can be regulated rendering imaging of multiple biomarkers at the same time[23] Another character of GNRs is that they are easy to be modified[21]. Porphyrins can be used as a multimodality nanoprobe in the therapeutic application, and have been widely employed in near-infrared fluorescence imaging due to their luminous characteristics[26] They can be detected in bodies, especially in tumors, for their preferential accumulation as well as amplifiable signals at tumor sites[26]. To our knowledge, this is the first time using trastuzumab binding onto the porphyrin-conjugated GNRs to figure out its efficacy and the thermal ablation in HER2-positive breast cancers. The study will hopefully promote current diagnostic and therapeutic strategies in management of trastuzumab-resistance breast cancer
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