Tumor-Targeting Peptides: Ligands for Molecular Imaging and Therapy

2018 ◽  
Vol 18 (1) ◽  
pp. 74-86 ◽  
Author(s):  
Ning Zhao ◽  
Yeshan Qin ◽  
Hongguang Liu ◽  
Zhen Cheng
Keyword(s):  
Clinical Trials ◽  
Tumor Cells ◽  
Tumor Targeting ◽  
Tumor Imaging ◽  
Therapeutic Agents ◽  
Cure Rate ◽  
High Affinity ◽  
Tumor Diagnostics ◽  
Tumor Tissues ◽  
Imaging Probes

The aberrant proliferation of tumor cells and abundant vasculature in tumor tissues are closely correlated with receptors that are specifically dysregulated in tumor cells. These tumor-associated targets are critical in early diagnosis and therapy selection. Ligands such as antibodies, proteins, polypeptides and polysaccharides that specifically bind to these targets can significantly improve the detection and cure rate when used as tumor imaging probes or anti-tumor agents. Compared to other targeting ligands, peptides have attracted increasingly more attention in tumor diagnostics and therapeutics because of their small sizes, high affinity, stability, ease of modification and low immunogenicity. Several peptide-based imaging probes and therapeutic agents have already been used in clinical trials. This review summarizes some of the tumor-associated targets and their corresponding peptides, as well as the potential of these peptides in cancer treatment.

scholarly journals Investigation of Specific Targeting of Triptorelin-Conjugated Dextran-Coated Magnetite Nanoparticles as a Targeted Probe in GnRH+ Cancer Cells in MRI

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Milad Yousefvand ◽  
Zahra Mohammadi ◽  
Farzaneh Ghorbani ◽  
Rasoul Irajirad ◽  
Hormoz Abedi ◽  
...  
Keyword(s):  
Contrast Agent ◽  
Cancer Cells ◽  
Cellular Uptake ◽  
Tumor Targeting ◽  
Tumor Imaging ◽  
Superparamagnetic Iron Oxide ◽  
Gnrh Receptors ◽  
Imaging Probes ◽  
Magnetic Resonance Imaging Mri ◽  
Targeted Contrast Agent

In recent years, the conjugation of superparamagnetic iron oxide nanoparticles (SPIONs), as tumor-imaging probes for magnetic resonance imaging (MRI), with tumor targeting peptides possesses promising advantages for specific delivery of MRI agents. The objective of the current study was to design a targeted contrast agent for MRI based on Fe3O4 nanoparticles conjugated triptorelin (SPION@triptorelin), which has a great affinity to the GnRH receptors. The SPIONs-coated carboxymethyl dextran (SPION@CMD) conjugated triptorelin (SPION@CMD@triptorelin) were synthesized using coprecipitation method and characterized by DLS, TEM, XRD, FTIR, Zeta, and VSM techniques. The relaxivities of synthetized formulations were then calculated using a 1.5 Tesla clinical magnetic field. MRI, quantitative cellular uptake, and cytotoxicity level of them were estimated. The characterization results confirmed that the formation of SPION@CMD@triptorelin has been conjugated with a suitable size. Our results demonstrated the lack of cellular cytotoxicity of SPION@CMD@triptorelin, and it could increase the cellular uptake of SPIONs to MDA-MB-231 cancer cells 6.50-fold greater than to SPION@CMD at the concentration of 75 μM. The relaxivity calculations for SPION@CMD@triptorelin showed a suitable r2 and r2/r1 with values of 31.75 mM−1·s−1 and 10.26, respectively. Our findings confirm that triptorelin-targeted SPIONs could provide a T2-weighted probe contrast agent that has the great potential for the diagnosis of GnRH-positive cancer in MRI.

scholarly journals Construction and Evaluation of the Tumor-Targeting, Cell-Penetrating Multifunctional Molecular Probe iCREKA

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Li-juan Wang ◽  
Hong-sheng Li ◽  
Quan-shi Wang ◽  
Hu-bing Wu ◽  
Yan-jiang Han ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Tumor Targeting ◽  
Cyclic Peptide ◽  
Tumor Imaging ◽  
Tumor Stroma ◽  
Molecular Probe ◽  
Fluorescence Signal ◽  
Glioma Tumor

A novel tumor stroma targeting and membrane-penetrating cyclic peptide, named iCREKA, was designed and labeled by fluorescein isothiocyanate (FITC) and positron emitter 18F to build the tumor-targeting tracers. The FITC-iCREKA was proved to have significantly higher cellular uptake in the glioma U87 cells in the presence of activated MMP-2 than that in absence of activated MMP-2 by cells fluorescence test in vitro. The tumor tissue fluorescence microscope imaging demonstrated that FITC-iCREKA accumulated in the walls of the blood vessels and the surrounding stroma in the glioma tumor at 1 h after intravenous injection. While at 3 h after injection, FITC-iCREKA was found to be uptaken in the tumor cells. However, the control FITC-CREKA can only be found in the tumor stroma, not in the tumor cells, no matter at 1 h or 3 h after injection. The whole-animal fluorescence imaging showed that the glioma tumor could be visualized clearly with high fluorescence signal. The microPET/CT imaging further demonstrated that 18F-iCREKA could target U87MG tumor in vivo from 30 min to 2 h after injection. The present study indicated the iCREKA had the capacity of tumor stroma targeting and the membrane-penetrating. It was potential to be developed as the fluorescent and PET tracers for tumor imaging.

Mesenchymal Stem Cells Mediated Drug Delivery in Tumor-Targeted Therapy

2020 ◽  
Vol 17 ◽  
Author(s):  
Mengying Xie ◽  
Lei Tao ◽  
Ziqi Zhang ◽  
Wei Wang
Keyword(s):  
Drug Delivery ◽  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Targeted Therapy ◽  
Cancer Therapy ◽  
Tumor Cells ◽  
Therapeutic Agents ◽  
Oncolytic Viruses ◽  
Tumor Tropism

: Mesenchymal stem cells (MSCs) possess unique properties that make them potential carriers for cancer therapy. MSCs have been documented to have low immunogenicity, positive safety in clinical trials, and the ability to selectively homing to inflammation and tumor sites. Thisreview aims to introduce tumor tropism mechanism and effects of MSCs on tumor cells, and give an overview of MSCs in delivering gene therapeutic agents, oncolytic viruses and chemotherapeutics, as well as the application of MSCs-derived exosomes in tumor-targeted therapy.

Nanoformulations can be utilized to deliver effective siRNA to tumor cells to decrease gene expression

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Gene Expression ◽  
Clinical Trials ◽  
Tumor Cells ◽  
Sirna Delivery ◽  
The Body ◽  
Passive Targeting ◽  
Delivery Vector ◽  
Tumor Tissues ◽  
Collaborative Efforts

siRNA-based gene therapy has gained interest in recent decades. Nanocarriers can be used to deliver rapid and efficient siRNA to tumor cells, suppressing gene expression. Some RNAi-based therapies are presently undergoing clinical trials. Clinical trials to preserve and distribute siRNA are increasingly focused on nanoformulations, and their safety has been promising. How nanocarriers avoid immune clearance and extend their circulation in the body is a key study topic for scientists.Most research relies on EPR-mediated passive targeting. However, as the MPS system sequesters most nanocarriers, the E PR effect can not be administered successfully in mice, which is a big human concern. Novel targeted approaches are desperately needed to accumulate siRNA in tumor tissues. In vitro and animal models, a number of TME-responsive siRNA nanocarriers were examined. Clinical nanomedicine is generally simple in structure and easy to mass-produce while preserving safety and effectiveness.It will require the collaborative efforts of materials scientists, basic medical scientists, and clinicians to develop the design of the ideal siRNA delivery vector, the authors suggest. The authors suggest that multimodal combination therapy has a stronger therapeutic impact on malignancies than a single therapy paradigm and might be "over-designed" for therapeutic usage. The study was published in Cancer Research.

scholarly journals 788 A novel T- lymphocyte binding aptamer assembled into a bispecifc compound for the treatment of solid tumors

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A823-A823
Author(s):  
Irit Carmi Levy ◽  
Erez Lavi ◽  
Neta Zilony Hanin ◽  
Zohar Pode ◽  
Karin Mizrahi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Solid Tumors ◽  
Tumor Cells ◽  
Tumor Targeting ◽  
Specific Antigen ◽  
Therapeutic Agents ◽  
List Type ◽  
Bispecific T Cell Engager

BackgroundT-cell engagers are bispecific molecules directed against the CD3 complex on one end and a tumor specific antigen on the other end, allowing a physical link of T cell to a tumor cell, resulting in tumor killing and immune activation. Bispecific molecules harnessing and redirecting T-cells towards tumor cells are a promising therapeutic agents. Aptamers are single stranded oligonucleotides with binding and recognition propensities similar to those of antibodies. Aptamers have a number of advantages over bispecific antibodies including shorter generation time and low immunogenicity. Thus, aptamers capable of targeting T cells would have great potential for use as anti-cancer therapeuticsMethodsSystematic evolution of ligands by exponential enrichment (SELEX) methodology was employed in order to identify a novel CD3e binding aptamer. CD3 binding aptamer was subsequently linked into a bispecific T cell engager structure with a tumor-targeting aptameric arm. The tumor-targeting aptamer is developed by Aummune's proprietary tailored therapeutic platform.1 based on identifying functional aptamer sequences capable of specifically killing targeted tumor cells and sparing healthy tissue .Exemplary bispecific aptamers were tested for T cell stimulation by flow cytometry. In vivo antitumor activity was investigated in syngeneic and in xenograft tumor models.ResultsWe have successfully identified a novel CD3e –targeting aptamer with a Kd of 31nM. A bispecific T cell engager comprised of this aptamer and a tumor-targeting aptamer induced a potent stimulation of T cells in vitro, resulting in CD69 upregulation and IFNg secretion.Next, the CD3e targeting aptamer was hybridized to tumoricidal aptamers identified by Aummune's platform (VS12) to target either the human colon carcinoma HCT116 cells or (VS32) the murine triple negative breast cancer 4T1 cells. Both bispecific entities (CS6-VS12 and CS6-VS32) effectively lead to inhibition of tumor growth in vivo and increased survival in the corresponding models.ConclusionsOur data above provide a proof-of-concept for Aummune's Bispecific Aptamer efficacy and provide a framework for the clinical development of this novel tailored immune therapeutic agents. Indeed, we are currently in the process of developing a first-in-human clinical study in subjects with solid tumors.ReferenceMamet N, et al, Commun Biol 2020.

scholarly journals Graphite-Coated Magnetic Nanoparticles as Multimodal Imaging Probes and Cooperative Therapeutic Agents for Tumor Cells

Small ◽  
2011 ◽  
Vol 7 (12) ◽  
pp. 1647-1652 ◽  
Author(s):  
Joung Kyu Park ◽  
Jongjin Jung ◽  
Prasad Subramaniam ◽  
Birju P. Shah ◽  
Cheoljin Kim ◽  
...  
Keyword(s):  
Magnetic Nanoparticles ◽  
Tumor Cells ◽  
Multimodal Imaging ◽  
Therapeutic Agents ◽  
Imaging Probes

scholarly journals Biological Evaluation of131I- and CF750-Labeled Dmab(scFv)-Fc Antibodies for Xenograft Imaging of CD25-Positive Tumors

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Qing Fan ◽  
Huawei Cai ◽  
Hao Yang ◽  
Lin Li ◽  
Cen Yuan ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Tumor Imaging ◽  
Recombinant Expression ◽  
Biological Evaluation ◽  
Tumor Uptake ◽  
Single Chain Variable Fragment ◽  
Single Chain ◽  
Tumor Xenografts ◽  
Tumor Tissues ◽  
Human Igg1

A Dmab(scFv)-Fc antibody containing the single chain variable fragment of a humanized daclizumab antibody and the Fc fragment of a human IgG1 antibody was produced via recombinant expression inPichia pastoris. The Dmab(scFv)-Fc antibody forms a dimer in solution, and it specifically binds CD25-positive tumor cells and tumor tissues. For tumor imaging, the Dmab(scFv)-Fc antibody was labeled with the 131I isotope and CF750 fluorescent dye, respectively. After intravenous injection of mice bearing CD25-positive tumor xenografts, tumor uptake of the131I-Dmab(scFv)-Fc antibody was visible at 1 h, and clear images were obtained at 5 h using SPECT/CT. After systemic administration of the CF750-Dmab(scFv)-Fc antibody, tumor uptake was present as early as 1 h, and tumor xenografts could be kinetically imaged within 9 h after injection. These results indicate that the Dmab(scFv)-Fc antibody rapidly and specifically targets CD25-positive tumor cells, suggesting the potential of this antibody as an imaging agent for the diagnosis of lymphomatous-type ATLL.

New fluorinated fructose analogs as selective probes of the hexose transporter protein GLUT5

2015 ◽  
Vol 13 (23) ◽  
pp. 6511-6521 ◽  
Author(s):  
Olivier-Mohamad Soueidan ◽  
Brendan J. Trayner ◽  
Tina N. Grant ◽  
Jeff R. Henderson ◽  
Frank Wuest ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Binding Site ◽  
Tumor Cells ◽  
Hexose Transporter ◽  
Transporter Protein ◽  
High Affinity ◽  
Cells In Culture ◽  
Molecular Imaging Probes ◽  
Imaging Probes

Two fluorinated fructose analogs are taken up by tumor cells in culture. Their high affinity for the transporter protein GLUT5 provides information on the structural demands of its binding site, and suggests approaches towards new molecular imaging probes.

Targeting p53-MDM2 Interaction Using Small Molecule Inhibitors and the Challenges Needed to be Addressed

2019 ◽  
Vol 20 (11) ◽  
pp. 1091-1111 ◽  
Author(s):  
Maryam Zanjirband ◽  
Soheila Rahgozar
Keyword(s):  
Clinical Trials ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Tp53 Gene ◽  
Therapeutic Agents ◽  
Negative Regulator ◽  
Mdm2 Protein ◽  
Independent Effects ◽  
Small Hydrophobic ◽  
Targeted Therapeutic

MDM2 protein is the core negative regulator of p53 that maintains the cellular levels of p53 at a low level in normal cells. Mutation of the TP53 gene accounts for 50% of all human cancers. In the remaining malignancies with wild-type TP53, p53 function is inhibited through other mechanisms. Recently, synthetic small molecule inhibitors have been developed which target a small hydrophobic pocket on MDM2 to which p53 normally binds. Given that MDM2-p53 antagonists have been undergoing clinical trials for different types of cancer, this review illustrates different aspects of these new cancer targeted therapeutic agents with the focus on the major advances in the field. It emphasizes on the p53 function, regulation of p53, targeting of the p53-MDM2 interaction for cancer therapy, and p53-dependent and -independent effects of inhibition of p53-MDM2 interaction. Then, representatives of small molecule MDM2-p53 binding antagonists are introduced with a focus on those entered into clinical trials. Furthermore, the review discusses the gene signatures in order to predict sensitivity to MDM2 antagonists, potential side effects and the reasons for the observed hematotoxicity, mechanisms of resistance to these drugs, their evaluation as monotherapy or in combination with conventional chemotherapy or with other targeted therapeutic agents. Finally, it highlights the certainly intriguing questions and challenges which would be addressed in future studies.

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