Her2-Functionalized Gold-Nanoshelled Magnetic Hybrid Nanoparticles: a Theranostic Agent for Dual-Modal Imaging and Photothermal Therapy of Breast Cancer

Dong, Quan; Yang, Hong; Wan, Caifeng; Zheng, Dongdong; Zhou, Zhiguo; Xie, Songqiang; Xu, Li; Du, Jing; Li, Fenghua

doi:10.1186/s11671-019-3053-4

Cited by 55 publications

(28 citation statements)

References 42 publications

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“…SKBR3 cells in competition group no longer showed distinctly fluorescence signals, which confirmed receptor-mediated targeting binding of Her2-GPH NCs and could be blocked by excess free anti-Her2 antibodies. 40 In addition, there was little fluorescence in MDA-MB-231 cells incubated with Her2-GPDH NCs (d), which confirmed the targeting specifically of Her2-GPDH NCs to Her2positive SKBR3 cells.…”

Section: Dox Loading and Releasementioning

confidence: 76%

Targeted gold nanoshelled hybrid nanocapsules encapsulating doxorubicin for bimodal imaging and near-infrared triggered synergistic therapy of Her2-positve breast cancer

et al. 2020

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A multifunctional targeted nanoplatform combining photothermal therapy and chemotherapy has emerged as a promising strategy for comprehensive therapies of breast cancer. In this study, we constructed human epidermal growth factor receptor 2 (Her2)-targeted gold nanoshelled poly(lactic- co-glycolic acid) hybrid nanocapsules encapsulating perfluorooctyl bromide, superparamagnetic iron oxide nanoparticles, and doxorubicin (Her2-GPDH nanocapsules) as theranostic agent for bimodal ultrasound/magnetic resonance imaging and synergistic photothermal-chemotherapy of Her2-postive breast cancer cells. Her2–GPDH nanocomposites possessed well-defined spherical morphology, and the average diameter was about 296 nm with good dispersion. Targeting assays demonstrated that Her2–GPDH nanocapsules exhibited higher targeting binding to Her2-positive SKBR3 cells than Her2-negative MDA-MB-231cells. The encapsulation efficiency and the loading content of doxorubicin in Her2–GPDH nanocapsules were 39 ± 1.45% and 3.8 ± 0.52%, respectively, and the agent exhibited pH-responsive and near-infrared light-triggered stepwise release behavior of doxorubicin. In vitro, the agent had potential to serve as feasible candidate for ultrasound imaging and T2-weighted magnetic resonance imaging with a relatively high relaxivity. Cell experiments confirmed that the agent had significant photothermal cytotoxicity on SKBR3 cells, and the combined photothermal–chemotherapy could significantly enhance the anti-tumor effect. In summary, the present Her2–GPDH nanocapsules, a novel multifunctional nanoplatform, will offer a new way for early bimodal molecular-level diagnosis and synergistic treatment of Her2-positve breast cancer.

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Section: Dox Loading and Releasementioning

confidence: 76%

Targeted gold nanoshelled hybrid nanocapsules encapsulating doxorubicin for bimodal imaging and near-infrared triggered synergistic therapy of Her2-positve breast cancer

et al. 2020

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“…Similarly, gold has been widely used in cancer treatment. 38 , 47 , 48 Compared with chemotherapy, photothermal effect mediated by gold has the advantage of repeatable treatment in a short time period with low toxicity and does not lead to drug resistance. In addition, studies 19 , 20 show that photothermal therapy can remodel the tumor microenvironment by decreasing the number of CAFs in the tumor, and enhance the accumulation of nanomedicine after the stroma decreased.…”

Section: Discussionmentioning

confidence: 99%

“…Preparation of Her2-DOX-SPIOs @PLGA@Au NPs Her2-DOX-SPIOs@PLGA@Au (Her2-DSG NPs) were prepared according to the previous report from our research group. 37,38 DOX-SPIOs@PLGA nanoparticles (DS NPs) were prepared using the single emulsion oil-inwater (O/W) solvent evaporation method. Hydrochloric acid doxorubicin (10 mg) reacted with triethylamine (20 μL) was transformed to oil phase from water phase.…”

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confidence: 99%

<p>Her2-Targeted Multifunctional Nano-Theranostic Platform Mediates Tumor Microenvironment Remodeling and Immune Activation for Breast Cancer Treatment</p>

Zheng

Wan

Yang

et al. 2020

IJN

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Purpose The treatment of breast cancer is often ineffective due to the protection of the tumor microenvironment and the low immunogenicity of tumor cells, leading to a poor therapeutic effect. In this study, we designed a nano-theranostic platform for these obstacles: a photothermal effect mediated by a gold shell could remodel the tumor microenvironment by decreasing cancer-associated fibroblasts (CAFs) and promote the release of doxorubicin (DOX) from nanoparticles. In addition, it could realize photoacoustic (PA)/MRI dual-model imaging for diagnose breast cancer and targeted identification of Her2-positive breast cancer. Methods Her2-DOX-superparamagnetic iron oxide nanoparticles (SPIOs)@Poly (D, L-lactide-co-glycolide) acid (PLGA)@Au nanoparticles (Her2-DSG NPs) were prepared based on a single emulsion oil-in-water (O/W) solvent evaporation method, gold seed growing method, and carbon diimide method. The size distribution, morphology, PA/MRI imaging, drug loading capacity, and drug release were investigated. Cytotoxicity, antitumor effect, cellular uptake, immunogenic cell death (ICD) effect, and targeted performance on human Her2-positive BT474 cell line were investigated in vitro. BT474/Adr cells were constructed and the antitumor effect of NPs on it was evaluated in vitro. Moreover, chemical-photothermal therapy effect, PA/MRI dual-model imaging, ICD effect induced by NPs, and tumor microenvironment remodeling in human BT474 breast cancer nude mice model were also investigated. Results Nanoparticles were spherical, uniform in size and covered with a gold shell. NPs had a photothermal effect, and can realize photothermal-controlled drug release in vitro. Chemical-photothermal therapy had a good antitumor effect on BT474/Adr cells and on BT474 cells in vitro. The targeting evaluation in vitro showed that Her2-DSG NPs could actively target and identify Her2-positive tumor cells. The PA/MRI imaging was successfully validated in vitro/vivo. Similarly, NPs could enhance the ICD effect in vitro/vivo, which could activate an immune response. Immunofluorescence results also proved that photothermal effect could decrease CAFs to remodel the tumor microenvironment and enhance the accessibility of NPs to tumor cells. According to the toxicity results, targeted drug delivery combined with photothermal-responsive drug release proved that NPs had good biosafety in vivo. Chemical-photothermal therapy of Her2-targeted NPs has a good antitumor effect in the BT474 nude mice model. Conclusion Our study showed that chemical-photothermal therapy combined with tumor microenvironment remodeling and immune activation based on the Her2-DSG NPs we developed are very promising for Her2-positive breast cancer.

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“…Previously, several studies reported the enhanced accumulation of functionalized tumor-targeted nanoparticles as compared to non-coated particles. 16,69,70 The effect of tumor targeting on biodistribution both biologically and mathematically will hence be the next important step in further studies, since ways to make intravenous injections viable may be a crucial part of making nanoparticle-based agents viable for clinical application.…”

Section: Discussionmentioning

confidence: 99%

<p>A New Pharmacokinetic Model Describing the Biodistribution of Intravenously and Intratumorally Administered Superparamagnetic Iron Oxide Nanoparticles (SPIONs) in a GL261 Xenograft Glioblastoma Model</p>

Klapproth

Shevtsov

Stangl

et al. 2020

IJN

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Background Superparamagnetic iron oxide nanoparticles (SPIONs) have displayed multifunctional applications in cancer theranostics following systemic delivery. In an effort to increase the therapeutic potential of local therapies (including focal hyperthermia), nanoparticles can also be administered intratumorally. Therefore, the development of a reliable pharmacokinetic model for the prediction of nanoparticle distribution for both clinically relevant routes of delivery is of high importance. Materials and Methods The biodistribution of SPIONs (of two different sizes – 130 nm and 60 nm) radiolabeled with zirconium-89 or technetium-99m following intratumoral or intravenous injection was investigated in C57/Bl6 mice bearing subcutaneous GL261 glioblastomas. Based on PET/CT biodistribution data, a novel pharmacokinetic model was established for a better understanding of the pharmacokinetics of the SPIONs after both administration routes. Results The PET image analysis of the nanoparticles (confirmed by histology) demonstrated the presence of radiolabeled nanoparticles within the glioma site (with low amounts in the liver and spleen) at all investigated time points following intratumoral injection. The mathematical model confirmed the dynamic nanoparticle redistribution in the organism over a period of 72 h with an equilibrium reached after 100 h. Intravenous injection of nanoparticles demonstrated a different distribution pattern with a rapid particle retention in all organs (particularly in liver and spleen) and a subsequent slow release rate. Conclusion The mathematical model demonstrated good agreement with experimental data derived from tumor mouse models suggesting the value of this tool to predict the real-time pharmacokinetic features of SPIONs in vivo. In the future, it is planned to adapt our model to other nanoparticle formulations to more precisely describe their biodistribution in in vivo model systems.

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Her2-Functionalized Gold-Nanoshelled Magnetic Hybrid Nanoparticles: a Theranostic Agent for Dual-Modal Imaging and Photothermal Therapy of Breast Cancer

Cited by 55 publications

References 42 publications

Targeted gold nanoshelled hybrid nanocapsules encapsulating doxorubicin for bimodal imaging and near-infrared triggered synergistic therapy of Her2-positve breast cancer

Targeted gold nanoshelled hybrid nanocapsules encapsulating doxorubicin for bimodal imaging and near-infrared triggered synergistic therapy of Her2-positve breast cancer

<p>Her2-Targeted Multifunctional Nano-Theranostic Platform Mediates Tumor Microenvironment Remodeling and Immune Activation for Breast Cancer Treatment</p>

<p>A New Pharmacokinetic Model Describing the Biodistribution of Intravenously and Intratumorally Administered Superparamagnetic Iron Oxide Nanoparticles (SPIONs) in a GL261 Xenograft Glioblastoma Model</p>

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