Radiation Crosslinked Smart Peptide Nanoparticles: A New Platform for Tumor Imaging

Nanoparticles have been employed to develop nanosensors and drug carriers that accumulate in tumors. Thus, it is necessary to control the particle size, surface potential, and biodegradability of these nanoparticles for effective tumor accumulation and safe medical application. In this study, to form a nanoparticle platform suitable for diagnostic and drug delivery system (DDS) applications, peptides composed of aromatic amino acid residues were designed and synthesized based on the radiation crosslinking mechanism of proteins. The peptide nanoparticles, which were produced by γ-ray irradiation, displayed a positive surface potential, maintained biodegradability, and were stable in water and phosphoric buffer solution during actual diagnosis. The surface potential of the peptide nanoparticles could be changed to negative by using a fluorescent labeling reagent, so that the fluorescent-labeled peptide nanoparticles were uptaken by HeLa cells. The radiation-crosslinked nanoparticles can be applied as a platform for tumor-targeting diagnostics and DDS therapy.

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Tumor-Targeted ZW800-1 Analog for Enhanced Tumor Imaging and Photothermal Therapy

Pharmaceutics ◽

10.3390/pharmaceutics13101648 ◽

2021 ◽

Vol 13 (10) ◽

pp. 1648

Author(s):

Min-Ho Park ◽

Gayoung Jo ◽

Eun-Jeong Kim ◽

Hoon Hyun

Keyword(s):

Tumor Targeting ◽

Near Infrared ◽

Tumor Imaging ◽

The Body ◽

Photothermal Effect ◽

Renal Elimination ◽

Surface Charges ◽

Nir Fluorescence ◽

Tumor Accumulation ◽

Targeting Ability

ZW800-1, a representative zwitterionic near-infrared (NIR) fluorophore, can minimize background tissue uptake owing to its balanced surface charges, and therefore, is widely used for improved NIR fluorescence imaging. As ZW800-1 has no tumor targetability, tumor imaging is highly dependent on the ability of the molecules conjugated to the ZW800-1. To enable tumor targeting using ZW800-1 without additional conjugation, we developed a tumor-targetable and renal-clearable ZW800-1 analog (ZW800-AM) based on the structural modification of ZW800-1. Specifically, an amine group on the center linker of the ZW800-1 indocyanine backbone was modified by replacing phenoxypropionic acid with tyramine linkage on the meso-chlorine atom. This modification improved the tumor targeting ability, which is known as the structure-inherent targeting strategy. More importantly, ZW800-AM not only showed sufficient tumor accumulation without nonspecific uptake but also produced a photothermal effect, killing tumor cells under 808 nm NIR laser irradiation. In addition, ZW800-AM exhibited rapid renal elimination from the body within 4 h of injection, similar to ZW800-1. Overall, the discovery of ZW800-AM as a bifunctional phototherapeutic agent may provide an ideal alternative for tumor-targeted imaging and phototherapy.

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280 Mechanisms of Tumor Targeting with Etirinotecan Pegol (NKTR-102): the Impact of Polymer Conjugation On Tumor Accumulation

European Journal of Cancer ◽

10.1016/s0959-8049(12)72078-6 ◽

2012 ◽

Vol 48 ◽

pp. 86

Author(s):

D. Fry ◽

J. Zhang ◽

H. Gursahani ◽

U. Hoch ◽

M. Eldon ◽

...

Keyword(s):

Tumor Targeting ◽

Etirinotecan Pegol ◽

Polymer Conjugation ◽

Tumor Accumulation ◽

The Impact

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

Contrast Media & Molecular Imaging ◽

10.1155/2021/5534848 ◽

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.

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Subtle changes in network composition impact the biodistribution and tumor accumulation of nanogels

Chemical Communications ◽

10.1039/c8cc05627g ◽

2018 ◽

Vol 54 (83) ◽

pp. 11777-11780 ◽

Cited By ~ 7

Author(s):

Ilona Zilkowski ◽

Ioanna Theodorou ◽

Krystyna Albrecht ◽

Frederic Ducongé ◽

Jürgen Groll

Keyword(s):

Breast Tumor ◽

Tumor Targeting ◽

Near Infrared ◽

Side Chain ◽

Human Breast ◽

Human Breast Tumor ◽

Tumor Xenografts ◽

Network Composition ◽

Tumor Accumulation

We studied the effect of subtle changes in side-chain chemistry and labelling with near infrared fluorophores of nanogels (NGs) prepared from thiolated poly(glycidol) on in vivo biodistribution in mice bearing human breast tumor xenografts. Side chain chemistry as well as labelling clearly influenced tumor targeting and overall biodistribution.

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Imaging, dosimetry, and radioimmunotherapy with iodine 131-labeled anti-CD37 antibody in B-cell lymphoma.

Journal of Clinical Oncology ◽

10.1200/jco.1992.10.11.1696 ◽

1992 ◽

Vol 10 (11) ◽

pp. 1696-1711 ◽

Cited By ~ 100

Author(s):

M S Kaminski ◽

L M Fig ◽

K R Zasadny ◽

K F Koral ◽

R B DelRosario ◽

...

Keyword(s):

B Cell ◽

Tumor Targeting ◽

Tumor Imaging ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Whole Body ◽

Tracer Dose ◽

Mixed Response ◽

Iodine 131 ◽

Grade 3

PURPOSE This study was undertaken to evaluate the tumor targeting, toxicity, and therapeutic potential of the anti-B-cell-reactive monoclonal antibody MB-1 (anti-CD37) labeled with iodine 131 given in a nonmarrow ablative dose range in B-cell lymphoma patients who relapsed after chemotherapy. PATIENTS AND METHODS Twelve patients with MB-1-reactive tumors were infused first with 40 mg of trace-labeled (3 to 7 mCi) MB-1. Ten patients who had no serious toxicity postinfusion and who had successful tumor imaging on serial gamma scans then received at least one 40-mg radioimmunotherapy (RIT) dose (25 to 161 mCi). Tracer estimates of delivered whole-body dose (WBD) were used in prescribing a millicurie RIT dose for seven patients. RESULTS Eleven patients had positive tumor imaging after a tracer dose, including patients with bulky tumors and/or large tumor burdens (> or = 1 kg) +/- splenomegaly. However, overall sensitivity for the detection of known tumor sites was only 39%. In six of eight patients with dose-assessable tumors, the radiation dose to at least one tumor was 1.1 to 3.1 times higher than to any normal organ, excluding the spleen for a 40-mg tracer dose. Tracer-dose toxicities included reversible glossal edema in one patient, grade 3 hepatic transaminasemia in another, and early drops in both circulating B and T cells (with decreases in B cells more pronounced) in nearly all patients. RIT toxicity was primarily myelosuppression (especially thrombocytopenia), which had a delayed onset and protracted recovery (without significant recovery until at least 2 months post-RIT). Grade 3 myelosuppression in two of two patients who were treated at a tracer-projected 50-cGy WBD level (133 and 149 mCi) precluded further planned RIT dose escalation. Less myelosuppression was generally observed in patients who were treated at < or = 40-cGy WBD levels. Antimouse antibodies developed in two patients. Six patients had tumor responses post-RIT. Four had responses that lasted more than 1 month (2 to 6 months), which included one complete response, one partial response, one minor response, and one mixed response. Responses seemed to occur more frequently in imaged tumors than in nonimaged tumors. The most durable response occurred in a patient who had the best antibody targeting to tumor. CONCLUSIONS Although 131I-MB-1 has limited diagnostic value, it can produce tumor responses at nonmarrow ablative RIT doses. Further studies that focus on improving tumor targeting with this or other B-cell-reactive radiolabeled antibodies and on ameliorating the myelosuppression associated with the RIT-dosing approach used in this trial are warranted.

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Formation and Stabilization of Gold Nanoparticles in Bovine Serum Albumin Solution

Molecules ◽

10.3390/molecules24183395 ◽

2019 ◽

Vol 24 (18) ◽

pp. 3395 ◽

Cited By ~ 8

Author(s):

Iulia Matei ◽

Cristina Maria Buta ◽

Ioana Maria Turcu ◽

Daniela Culita ◽

Cornel Munteanu ◽

...

Keyword(s):

Gold Nanoparticles ◽

Bovine Serum Albumin ◽

Serum Albumin ◽

Bovine Serum ◽

Particle Growth ◽

Protective Role ◽

Amino Acid Residues ◽

Buffer Solution ◽

Paramagnetic Resonance ◽

Tem Microscopy

The formation and growth of gold nanoparticles (AuNPs) were investigated in pH 7 buffer solution of bovine serum albumin (BSA) at room temperature. The processes were monitored by UV-Vis, circular dichroism, Raman and electron paramagnetic resonance (EPR) spectroscopies. TEM microscopy and dynamic light scattering (DLS) measurements were used to evidence changes in particle size during nanoparticle formation and growth. The formation of AuNPs at pH 7 in the absence of BSA was not observed, which proves that the albumin is involved in the first step of Au(III) reduction. Changes in the EPR spectral features of two spin probes, CAT16 and DIS3, with affinity for BSA and AuNPs, respectively, allowed us to monitor the particle growth and to demonstrate the protective role of BSA for AuNPs. The size of AuNPs formed in BSA solution increases slowly with time, resulting in nanoparticles of different morphologies, as revealed by TEM. Raman spectra of BSA indicate the interaction of albumin with AuNPs through sulfur-containing amino acid residues. This study shows that albumins act as both reducing agents and protective corona of AuNPs.

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Key-Protease Inhibition Regimens Promote Tumor Targeting of Neurotensin Radioligands

Pharmaceutics ◽

10.3390/pharmaceutics12060528 ◽

2020 ◽

Vol 12 (6) ◽

pp. 528

Author(s):

Panagiotis Kanellopoulos ◽

Aikaterini Kaloudi ◽

Marion de Jong ◽

Eric P. Krenning ◽

Berthold A. Nock ◽

...

Keyword(s):

Tumor Targeting ◽

Ace Inhibitor ◽

Tumor Imaging ◽

Colon Adenocarcinoma ◽

Ace Inhibition ◽

Tumor Uptake ◽

Protease Inhibition ◽

Structural Modifications

Neurotensin subtype 1 receptors (NTS1R) represent attractive molecular targets for directing radiolabeled neurotensin (NT) analogs to tumor lesions for diagnostic and therapeutic purposes. This approach has been largely undermined by the rapid in vivo degradation of linear NT-based radioligands. Herein, we aim to increase the tumor targeting of three 99mTc-labeled NT analogs by the in-situ inhibition of two key proteases involved in their catabolism. DT1 ([N4-Gly7]NT(7-13)), DT5 ([N4-βAla7,Dab9]NT(7-13)), and DT6 ([N4-βAla7,Dab9,Tle12]]NT(7-13)) were labeled with 99mTc. Their profiles were investigated in NTS1R-positive colon adenocarcinoma WiDr cells and mice treated or not with the neprilysin (NEP)-inhibitor phosphoramidon (PA) and/or the angiotensin converting enzyme (ACE)-inhibitor lisinopril (Lis). Structural modifications led to the partial stabilization of 99mTc-DT6 in peripheral mice blood (55.1 ± 3.9% intact), whereas 99mTc-DT1 and 99mTc-DT5 were totally degraded within 5 min. Coinjection of PA and/or Lis significantly stabilized all three analogs, leading to a remarkable enhancement of tumor uptake for 99mTc-DT1 and 99mTc-DT5, but was less effective in the case of poorly internalizing 99mTc-DT6. In conclusion, NEP and/or ACE inhibition represents a powerful tool to improve tumor targeting and the overall pharmacokinetics of NT-based radioligands, and warrants further validation in the field of NTS1R-targeted tumor imaging and therapy.

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

Contrast Media & Molecular Imaging ◽

10.1155/2018/7929617 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 2

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.

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