scholarly journals DARPin_9-29-Targeted Gold Nanorods Selectively Suppress HER2-Positive Tumor Growth in Mice

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5235
Author(s):  
Galina M. Proshkina ◽  
Elena I. Shramova ◽  
Marya V. Shilova ◽  
Ivan V. Zelepukin ◽  
Victoria O. Shipunova ◽  
...  

Near-infrared phototherapy has great therapeutic potential for cancer treatment. However, for efficient application, in vivo photothermal agents should demonstrate excellent stability in blood and targeted delivery to pathological tissue. Here, we demonstrated that stable bovine serum albumin-coated gold mini nanorods conjugated to a HER2-specific designed ankyrin repeat protein, DARPin_9-29, selectively accumulate in HER2-positive xenograft tumors in mice and lead to a strong reduction in the tumor size when being illuminated with near-infrared light. The results pave the way for the development of novel DARPin-based targeted photothermal therapy of cancer.

2017 ◽  
Vol 114 (15) ◽  
pp. E3110-E3118 ◽  
Author(s):  
Moustafa R. K. Ali ◽  
Mohammad Aminur Rahman ◽  
Yue Wu ◽  
Tiegang Han ◽  
Xianghong Peng ◽  
...  

Gold nanorods (AuNRs)-assisted plasmonic photothermal therapy (AuNRs-PPTT) is a promising strategy for combating cancer in which AuNRs absorb near-infrared light and convert it into heat, causing cell death mainly by apoptosis and/or necrosis. Developing a valid PPTT that induces cancer cell apoptosis and avoids necrosis in vivo and exploring its molecular mechanism of action is of great importance. Furthermore, assessment of the long-term fate of the AuNRs after treatment is critical for clinical use. We first optimized the size, surface modification [rifampicin (RF) conjugation], and concentration (2.5 nM) of AuNRs and the PPTT laser power (2 W/cm2) to achieve maximal induction of apoptosis. Second, we studied the potential mechanism of action of AuNRs-PPTT using quantitative proteomic analysis in mouse tumor tissues. Several death pathways were identified, mainly involving apoptosis and cell death by releasing neutrophil extracellular traps (NETs) (NETosis), which were more obvious upon PPTT using RF-conjugated AuNRs (AuNRs@RF) than with polyethylene glycol thiol-conjugated AuNRs. Cytochrome c and p53-related apoptosis mechanisms were identified as contributing to the enhanced effect of PPTT with AuNRs@RF. Furthermore, Pin1 and IL18-related signaling contributed to the observed perturbation of the NETosis pathway by PPTT with AuNRs@RF. Third, we report a 15-month toxicity study that showed no long-term toxicity of AuNRs in vivo. Together, these data demonstrate that our AuNRs-PPTT platform is effective and safe for cancer therapy in mouse models. These findings provide a strong framework for the translation of PPTT to the clinic.


2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Songtao Zhang ◽  
Longhai Jin ◽  
Jianhua Liu ◽  
Yang Liu ◽  
Tianqi Zhang ◽  
...  

AbstractIn spite of the tumor microenvironments responsive cancer therapy based on Fenton reaction (i.e., chemodynamic therapy, CDT) has been attracted more attentions in recent years, the limited Fenton reaction efficiency is the important obstacle to further application in clinic. Herein, we synthesized novel FeO/MoS2 nanocomposites modified by bovine serum albumin (FeO/MoS2-BSA) with boosted Fenton reaction efficiency by the synergistic effect of co-catalyze and photothermal effect of MoS2 nanosheets triggered by the second near-infrared (NIR II) light. In the tumor microenvironments, the MoS2 nanosheets not only can accelerate the conversion of Fe3+ ions to Fe2+ ions by Mo4+ ions on their surface to improve Fenton reaction efficiency, but also endow FeO/MoS2-BSA with good photothermal performances for photothermal-enhanced CDT and photothermal therapy (PTT). Consequently, benefiting from the synergetic-enhanced CDT/PTT, the tumors are eradicated completely in vivo. This work provides innovative synergistic strategy for constructing nanocomposites for highly efficient CDT.


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Mary K. Popp ◽  
Imane Oubou ◽  
Colin Shepherd ◽  
Zachary Nager ◽  
Courtney Anderson ◽  
...  

Photothermal therapy (PTT) treatments have shown strong potential in treating tumors through their ability to target destructive heat preferentially to tumor regions. In this paper we demonstrate that PTT in a murine melanoma model using gold nanorods (GNRs) and near-infrared (NIR) light decreases tumor volume and increases animal survival to an extent that is comparable to the current generation of melanoma drugs. GNRs, in particular, have shown a strong ability to reach ablative temperatures quickly in tumors when exposed to NIR light. The current research tests the efficacy of GNRs PTT in a difficult and fast growing murine melanoma model using a NIR light-emitting diode (LED) light source. LED light sources in the NIR spectrum could provide a safer and more practical approach to photothermal therapy than lasers. We also show that the LED light source can effectively and quickly heatin vitroandin vivomodels to ablative temperatures when combined with GNRs. We anticipate that this approach could have significant implications for human cancer therapy.


Small ◽  
2008 ◽  
Vol 4 (7) ◽  
pp. 1001-1007 ◽  
Author(s):  
Takuro Niidome ◽  
Yasuyuki Akiyama ◽  
Kohei Shimoda ◽  
Takahito Kawano ◽  
Takeshi Mori ◽  
...  

Nanomaterials ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 582 ◽  
Author(s):  
Álvaro Cárcamo-Martínez ◽  
Juan Domínguez-Robles ◽  
Brónach Mallon ◽  
Md. Taifur Raman ◽  
Ana Sara Cordeiro ◽  
...  

Current strategies for the treatment of superficial non-melanoma skin cancer (NMSC) lesions include topical imoquimod, 5-fluorouracil, and photodynamic therapy. Although these treatments are effective, burning pain, blistering, and dermatitis have been reported as frequent side effects, making these therapies far from ideal. Plasmonic materials have been investigated for the induction of hyperthermia and use in cancer treatment. In this sense, the effectiveness of intratumorally and systemically injected gold nanorods (GnRs) in inducing cancer cell death upon near-infrared light irradiation has been confirmed. However, the in vivo long-term toxicity of these particles has not yet been fully documented. In the present manuscript, GnRs were included in a crosslinked polymeric film, evaluating their mechanical, swelling, and adhesion properties; moreover, their ability to heat up neonatal porcine skin (such as a skin model) upon irradiation was tested. Inclusion of GnRs into the films did not affect mechanical or swelling properties. GnRs were not released after film swelling, as they remained entrapped in the polymeric network; moreover, films did not adhere to porcine skin, altogether showing the enhanced biocompatibility of the material. GnR-loaded films were able to heat up the skin model over 40 °C, confirming the potential of this system for non-invasive local hyperthermia applications.


2016 ◽  
Vol 4 (27) ◽  
pp. 4667-4674 ◽  
Author(s):  
Hui-Jing Xiang ◽  
Min Guo ◽  
Lu An ◽  
Shi-Ping Yang ◽  
Qian-Ling Zhang ◽  
...  

NIR light induced spatiotemporal delivery of NO to lysosome accompanied by hyperthermia was realized.


2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Oshra Betzer ◽  
Rinat Ankri ◽  
Menachem Motiei ◽  
Rachela Popovtzer

A critical problem in the treatment of cancer is the inability to identify microsized tumors and treat them without normal tissue destruction. While surgical excision of tumors is highly effective, residual micrometastases and remaining positive margins are the main cause of recurrence. In this study, we propose a theranostic approach for the detection and therapy of head and neck cancer (HNC). We developed a plasmonic-based nanoplatform for combined, ultrasensitivein vivospectroscopic detection and targeted therapy of HNC. This detection method involves near-infrared (NIR) spectroscopy of gold nanorods (GNRs) that selectively target and attach to squamous cell carcinoma HNC cells, through an immune complex. Diagnosis is based on a spectral shift analysis, which is generated by interparticle-plasmon-resonance patterns of the specifically targeted GNRs. Additionally, the ability to design the GNRs to strongly absorb light in the NIR region enables efficient irradiation of these GNRs, for selective photothermal therapy (PTT) of the cancer cells. We expect this targeted, noninvasive, and nonionizing spectroscopic detection method to provide a highly sensitive and simple diagnostic tool for micrometastasis. In addition, the concomitant development of targeted PTT, based on specific cancer markers, may pave the way for tailoring effective therapy for patients, toward an era of personalized medicine.


2012 ◽  
Vol 22 (31) ◽  
pp. 16095 ◽  
Author(s):  
Hongyan Tang ◽  
Shun Shen ◽  
Jia Guo ◽  
Baisong Chang ◽  
Xinguo Jiang ◽  
...  

2008 ◽  
Vol 1138 ◽  
Author(s):  
Takuro Niidome ◽  
Yasuyuki Akiyama ◽  
Kohei Shimoda ◽  
Takahito Kawano ◽  
Takeshi Mori ◽  
...  

AbstractGold nanorods have a strong surface plasmon band at the near infrared region. The absorbed light energy is then converted to heat. Since near infrared light can penetrate deeply into tissue, gold nanorods are expected to be used as a contrast agent for bioimaging using the near infrared light and photosensitizers for photothermal therapy. The surface plasmon bands of intravenously injected the gold nanorods were directly monitored from the mouse abdomen by using a spectrophotometer equipped with an integrating sphere. The absorbance at 900 nm from PEG5,000-modified gold nanorods immediately increased after injection and reached a plateau. The injection of phosphatidylcholine-modified gold nanorods also increased the absorbance at 900 nm, but the absorbance decreased single exponentially with a 1.3-min half-life. To demonstrate photothermal tumor therapy, the PEG-modified gold nanorods were directly injected into subcutaneous tumors in mice, then, near infrared laser light was irradiated to the tumor. After the treatment, significant suppression of tumor growth was observed.


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