Microarray Based Screening of Peptide Nano Probes for HER2 Positive Tumor

Wang, Zihua; Wang, Weizhi; Bu, Xiangli; Wei, Zewen; Geng, Li; Wu, Yue; Dong, Chengyan; Li, Liqiang; Zhang, Di; Yang, Shu Hua; Wang, Fan; Lausted, Christopher; Hood, Leroy; Hu, Zhiyuan

doi:10.1021/acs.analchem.5b01588

Cited by 49 publications

(40 citation statements)

References 52 publications

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“…Other amino acids such as Ser, His, Arg, Tyr, Thr, Asp, and Asn were used to increase peptide diversity. 39 Either the N- or C-terminus of the peptides were connected by a conformationally rigid spacer group, such as PFP, PNP, PYP, and PWP, in the middle region. We evaluated binding interactions of these candidates to HER2-ECD using Pepsite-2.…”

Section: Resultsmentioning

confidence: 99%

Design and Synthesis of Near-Infrared Peptide for in Vivo Molecular Imaging of HER2

et al. 2015

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We report the development, characterization, and validation of a peptide specific for the extracellular domain of HER2. This probe chemistry was developed for molecular imaging by using a structural model to select an optimal combination of amino acids that maximize the likelihood for unique hydrophobic and hydrophilic interactions with HER2 domain 3. The sequence KSPNPRF was identified and conjugated with either FITC or Cy5.5 via a GGGSK linker using Fmoc-mediated solid-phase synthesis to demonstrate fiexibility for this chemical structure to be labeled with different fluorophores. A scrambled sequence was developed for control by altering the conformationally rigid spacer and moving both hydrophobic and hydrophilic amino acids on the C-terminus. We validated peptide specificity for HER2 in knockdown and competition experiments using human colorectal cancer cells in vitro, and measured a binding affinity of kd = 21 nM and time constant of k = 0.14 min−1 (7.14 min). We used this peptide with either topical or intravenous administration in a preclinical model of colorectal cancer to demonstrate specific uptake in spontaneous adenomas and to show feasibility for real time in vivo imaging with near-infrared fluorescence. We used this peptide in immunofluorescence studies of human proximal colon specimens to evaluate specificity for sessile serrated and sporadic adenomas. Improved visualization can be used endoscopically to guide tissue biopsy and detect premalignant lesions that would otherwise be missed. Our peptide design for specificity to HER2 is promising for clinical translation in molecular imaging methods for early cancer detection.

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Section: Resultsmentioning

confidence: 99%

Design and Synthesis of Near-Infrared Peptide for in Vivo Molecular Imaging of HER2

et al. 2015

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“…In both cell-staining and flow cytometry studies, FITC-H6F exhibited tumor cell-binding features but a lower affinity for receptors than FITC-trastuzumab. In HER2-positive SKBR3 breast cells, there is a significant decrease in FITC-H6F fluorescence signals on transfection of the recombinant plasmid pRNAi-HER2 in HER2-positive SKBR3 breast cells, confirming that the HER2 protein is the specific target of the H6F peptide (22). Furthermore, the introduction of HYNIC to the original H6F peptide did not significantly affect its binding affinity to the HER2 protein (Fig.…”

Section: Discussionmentioning

confidence: 68%

“…The H6F peptide and fluorescein isothiocyanate (FITC)-H6F were synthesized as previously described (22). The H6F peptide was then conjugated with SBz-HYNIC using a standard procedure (23).…”

Section: Preparation Of 99m Tc-hydrazinonicotinamide (Hynic)-h6fmentioning

confidence: 99%

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SPECT/CT Imaging of the Novel HER2-Targeted Peptide Probe ^99mTc-HYNIC-H6F in Breast Cancer Mouse Models

Wang

et al. 2017

J Nucl Med

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Overexpression of human epidermal growth factor receptor 2 (HER2) plays important roles in tumorigenesis and tumor progression in breast cancer. Nuclear imaging of HER2 expression in tumors might detect all HER2-positive tumors throughout the body and guide HER2-targeted therapies for patients. We therefore aimed to develop a HER2-targeted peptide probe for breast cancer imaging. A novel SPECT imaging probe, 99m Tc-HYNIC-H6F, was prepared and then evaluated in breast cancer animal models. Methods: The HER2-targeted peptide H6F (YLFFVFER) was conjugated with the bifunctional chelator hydrazinonicotinamide (HYNIC). 99m Tc-HYNIC-H6F was prepared, and the in vivo characteristics of 99m Tc-HYNIC-H6F were investigated in MDA-MB-453 (HER2-positive) and MDA-MB-231 (HER2-negative) models using small-animal SPECT/CT. Moreover, to investigate the specificity of the H6F peptide toward HER2 and the potential applications in monitoring therapies involving trastuzumab, unlabeled H6F and trastuzumab were used as blocking agents in cell competition studies and SPECT imaging. Results: A standard tricine/trisodium triphenylphosphine-3,39,3$-trisulfonate labeling procedure demonstrated that the radiochemical purity was greater than 95%. 99m Tc-HYNIC-H6F displayed excellent HER2-binding specificity both in vitro and in vivo. SPECT/ CT imaging revealed that the MDA-MB-453 tumors were clearly visualized (percentage injected dose per gram, 3.58 6 0.01 at 30 min after injection), whereas the signals in HER2-negative MDA-MB-231 tumors were much lower (0.73 6 0.22 at 30 min after injection). Tumor uptake of MDA-MB-453 was blocked by the coinjection of excess H6F but not by excess trastuzumab. Conclusion: The 99m Tc-HYNIC-H6F peptide probe specifically accumulates in HER2-positive tumors and is therefore promising for the diagnosis of HER2-positive cancers. Because 99m Tc-HYNIC-H6F and trastuzumab target different regions of the HER2 receptor, this radiotracer also has great potential for monitoring the therapeutic efficacy of trastuzumab by rechecking the expression level of HER2 without blocking effect during therapy. Br east cancer is the most frequent cancer and the second leading cause of cancer death among women worldwide. The great progress in breast cancer screening and early diagnosis in recent decades has significantly increased life expectancy and patient quality of life (1,2). The best-studied tumor-associated antigen in breast cancer is human epidermal growth factor receptor 2 (HER2), which is positive in approximately 20%-30% of all breast cancers (3-5). Moreover, overexpression of HER2 is also characterized as a major negative prognostic factor that is associated with higher mortality in early-stage disease, increased incidence of metastasis, and reduced time to relapse (6-8). Trastuzumab (Herceptin; Genentech), the first approved HER2-targeted humanized monoclonal antibody, is the standard-of-care treatment for patients with HER2-positive breast cancer. In several trials, trastuzumab has proven effective in combination with...

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“…In addition, SPNs have been developed into smart anticancer materials through the introduction of activatable linkers that can be cleaved only in the tumor microenvironment or upon light irradiation . Tamoxifen (Tam) is a non‐steroidal triphenylethylene derivative and was the first selective estrogen receptor modulator whereas Herceptin targets HER2 for the treatment of breast cancer . Vivek and co‐workers developed HER2‐targeting poly(vinylpyrrolidone) (PVP)–poly( d , l ‐lactic‐ co ‐glycolic acid) (PLGA) nanoparticular drug delivery system, with the combination of Tam (targeting agent) and Herceptin (enhances the cytoplasmic delivery of post‐endocytosed nanoparticles loaded with Tam) enhancing the therapeutic efficacy toward HER2‐positive metastatic breast cancer cells.…”

Section: Antibody‐conjugated Nanomaterialsmentioning

confidence: 99%

Bio‐Conjugated Advanced Materials for Targeted Disease Theranostics

Kwon

Yan

et al. 2020

Adv Funct Materials

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Human beings are “machines” that use endogenously produced biomolecules as “components” in signaling and for the maintenance of the body. These biomolecules consist of proteins, nucleic acids, and carbohydrates, which can either be extracted from biological substrates or synthesized by chemical/biochemical methods. These biomolecules have the ability to recognize/interact with other biomolecules that are overexpressed in disease cells. For targeted theranostics, strategies to chemically incorporate these natural biomolecules with advanced materials to treat human diseases by imaging‐guided drug delivery or photodynamic/photothermal therapy are proposed, with improved biocompatibility. Herein, recent research on construction of quantum dots, nanoparticles, and 2D material platforms decorated with antibodies, peptides, nucleic acid aptamers, carbohydrates, and folic acid for targeted diagnosis and treatment are summarized and discussed. In addition, the various strategies required to construct effective functional materials for targeted cancer therapy are highlighted. The hope is that this review can inspire and guide those that are interested in the field of biomedicine to rationally design and develop new target‐based theranostic materials.

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Microarray Based Screening of Peptide Nano Probes for HER2 Positive Tumor

Cited by 49 publications

References 52 publications

Design and Synthesis of Near-Infrared Peptide for in Vivo Molecular Imaging of HER2

Design and Synthesis of Near-Infrared Peptide for in Vivo Molecular Imaging of HER2

SPECT/CT Imaging of the Novel HER2-Targeted Peptide Probe ^99mTc-HYNIC-H6F in Breast Cancer Mouse Models

Bio‐Conjugated Advanced Materials for Targeted Disease Theranostics

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Microarray Based Screening of Peptide Nano Probes for HER2 Positive Tumor

Cited by 49 publications

References 52 publications

Design and Synthesis of Near-Infrared Peptide for in Vivo Molecular Imaging of HER2

Design and Synthesis of Near-Infrared Peptide for in Vivo Molecular Imaging of HER2

SPECT/CT Imaging of the Novel HER2-Targeted Peptide Probe 99mTc-HYNIC-H6F in Breast Cancer Mouse Models

Bio‐Conjugated Advanced Materials for Targeted Disease Theranostics

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SPECT/CT Imaging of the Novel HER2-Targeted Peptide Probe ^99mTc-HYNIC-H6F in Breast Cancer Mouse Models