A novel peptide targeting gastrin releasing peptide receptor for pancreatic neoplasm detection

2020 ◽  
Vol 8 (9) ◽  
pp. 2682-2693 ◽  
Author(s):  
Yuanbiao Tu ◽  
Ji Tao ◽  
Fang Wang ◽  
Peifei Liu ◽  
Zhihao Han ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Targeting ◽  
Pancreatic Neoplasm ◽  
Metabolic Stability ◽  
Peptide Receptor ◽  
Gastrin Releasing Peptide ◽  
Cancer Models ◽  
Pharmacokinetic Properties ◽  
Targeting Ability ◽  
Peptide Targeting

The designed novel peptide GB-6 with targeted GRPR-binding possesses more favorable pharmacokinetic properties and metabolic stability, as well as superior tumor-targeting ability in pancreatic cancer models, relative to BBN7–14.

GRPR-targeted SPECT imaging using a novel bombesin-based peptide for colorectal cancer detection

2020 ◽  
Vol 8 (23) ◽  
pp. 6764-6772 ◽  
Author(s):  
Peifei Liu ◽  
Yuanbiao Tu ◽  
Ji Tao ◽  
Zicun Liu ◽  
Fang Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Detection ◽  
Tumor Targeting ◽  
Spect Imaging ◽  
Intestinal Activity ◽  
Cancer Models ◽  
Pharmacokinetic Properties ◽  
Targeting Peptide ◽  
Targeting Ability

The designed novel targeting peptide GB-6 binding to GRPR possesses more favorable pharmacokinetic properties with lower intestinal activity as well as superior tumor-targeting ability in colorectal cancer models than BBN7–14.

scholarly journals One Step Closer to Clinical Translation: Enhanced Tumor Targeting of [99mTc]Tc-DB4 and [111In]In-SG4 in Mice Treated with Entresto

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1145
Author(s):  
Panagiotis Kanellopoulos ◽  
Aikaterini Kaloudi ◽  
Maritina Rouchota ◽  
George Loudos ◽  
Marion de Jong ◽  
...  
Keyword(s):  
Tumor Targeting ◽  
Metabolic Stability ◽  
Clinical Translation ◽  
Tumor Uptake ◽  
Gastrin Releasing Peptide ◽  
Cognate Receptor ◽  
One Step ◽  
The Stability ◽  
The Impact

Background: Peptide radioligands may serve as radionuclide carriers to tumor sites overexpressing their cognate receptor for diagnostic or therapeutic purposes. Treatment of mice with the neprilysin (NEP)-inhibitor phosphoramidon was previously shown to improve the metabolic stability and tumor uptake of biodegradable radiopeptides. Aiming to clinical translation of this methodology, we herein investigated the impact of the approved pill Entresto, releasing the potent NEP-inhibitor LBQ657 in vivo, on the stability and tumor uptake of two radiopeptides. Methods: The metabolic stability of [99mTc]Tc-DB4 (DB4, N4-Pro-Gln-Arg-Tyr-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Nle-NH2) and [111In]In-SG4 (SG4, DOTA-DGlu-Ala-Tyr-Gly-Trp-Nle-Asp-Phe-NH2) was tested in LBQ657/Entresto-treated mice vs. untreated controls. The uptake in gastrin-releasing peptide receptor (GRPR)-, or cholecystokinin subtype 2 receptor (CCK2R)-positive tumors respectively, was compared between LBQ657/Entresto-treated mice and untreated controls. Results: LBQ657/Entresto treatment induced marked stabilization of [99mTc] Tc-DB4 and [111In]In-SG4 in peripheral mice blood, resulting in equally enhanced tumor uptake at 4 h post-injection. Accordingly, the [99mTc]Tc-DB4 uptake of 7.13 ± 1.76%IA/g in PC-3 tumors increased to 16.17 ± 0.71/17.50 ± 3.70%IA/g (LBQ657/Entresto) and the [111In]In-SG4 uptake of 3.07 ± 0.87%IA/g in A431-CCK2R(+) tumors to 8.11 ± 1.45/9.61 ± 1.70%IA/g. Findings were visualized by SPECT/CT. Conclusions: This study has shown the efficacy of Entresto to notably improve the profile of [99mTc]Tc-DB4 and [111In]In-SG4 in mice, paving the way for clinical translation of this approach.

iRGD Co-Administration with Paclitaxel-Loaded PLGA Nanoparticles Enhance Targeting and Antitumor Effect in Colorectal Cancer Treatment

2020 ◽  
Vol 20 ◽  
Author(s):  
Li Li ◽  
Mi Yang ◽  
Rutian Li ◽  
Jing Hu ◽  
Lixia Yu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Targeting ◽  
Antitumor Effect ◽  
Plga Nanoparticles ◽  
Specific Targeting ◽  
Cancer Models ◽  
Cell Experiment ◽  
Targeting Ability ◽  
Targeting Effect ◽  
Colorectal Cancer Treatment

Objective: To explore the targeting effect of PLGA-NP and iRGD co-administration with PTX-PLGA NP (PTX-PLGA + iRGD) on colorectal cancer. Methods: Whether PLGA-NP co-administration with iRGD peptide could show effective tumor-targeting ability in contrast to with PLGA-NP in colorectal cancer mice models was evaluated. Moreover, the chemotherapeutics paclitaxel (PTX) was loaded into the PLGA-NP to impart anti-tumor efficiency to the PTX-PLGA. Whether iRGD co-administration with PTX-PLGA NP (PTX-PLGA + iRGD) in colorectal cancer models enabled PTX to achieve better anti-tumor efficiency and biocompatibility was further assessed. Results: The targeting ability of PLGA-NP was enhanced in cell experiment and colorectal cancer mice models by coadministration of iRGD. As a result, PTX-PLGA + iRGD achieved better anti-tumor efficacy than PTX and PTX-PLGA. Conlusion: The nanocarrier based on PLGA with specific targeting ability could promote the clinical application of various chemotherapeutics similar to PTX. The combination of drug-loaded nanoparticles and iRGD could develop into a promising drug delivery system.

scholarly journals A Liposomal Gemcitabine, FF-10832, Improves Plasma Stability, Tumor Targeting, and Antitumor Efficacy of Gemcitabine in Pancreatic Cancer Xenograft Models

2021 ◽  
Author(s):  
Takeshi Matsumoto ◽  
Takashi Komori ◽  
Yuta Yoshino ◽  
Tadaaki Ioroi ◽  
Tsukasa Kitahashi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Antitumor Activity ◽  
Tumor Targeting ◽  
Laser Scanning ◽  
Laser Scanning Microscopy ◽  
Human Pancreatic Cancer ◽  
Confocal Laser ◽  
Long Term Stability ◽  
Pharmacokinetic Properties ◽  
The Stability

Abstract Purpose The clinical application of gemcitabine (GEM) is limited by its pharmacokinetic properties. The aim of this study was to characterize the stability in circulating plasma, tumor targeting, and payload release of liposome-encapsulated GEM, FF-10832. Methods Antitumor activity was assessed in xenograft mouse models of human pancreatic cancer. The pharmacokinetics of GEM and its active metabolite dFdCTP were also evaluated. Results In mice with Capan-1 tumors, the dose-normalized areas under the curve (AUCs) after FF-10832 administration in plasma and tumor were 672 and 1047 times higher, respectively, than after using unencapsulated GEM. The tumor-to-bone marrow AUC ratio of dFdCTP was approximately eight times higher after FF-10832 administration than after GEM administration. These results indicated that liposomal encapsulation produced long-term stability in circulating plasma and tumor-selective targeting of GEM. In mice with Capan-1, SUIT-2, and BxPC-3 tumors, FF-10832 had better antitumor activity and tolerability than GEM. Internalization of FF-10832 in tumor-associated macrophages (TAMs) was revealed by flow cytometry and confocal laser scanning microscopy, and GEM was efficiently released from isolated macrophages of mice treated with FF-10832. These results suggest that TAMs are one of the potential reservoirs of GEM in tumors. Conclusion This study found that FF-10832 had favorable pharmacokinetic properties. The liposomal formulation was more effective and tolerable than unencapsulated GEM in mouse xenograft tumor models. Hence, FF-10832 is a promising candidate for the treatment of pancreatic cancer.

scholarly journals The Revolutionary Roads to Study Cell–Cell Interactions in 3D In Vitro Pancreatic Cancer Models

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 930
Author(s):  
Donatella Delle Cave ◽  
Riccardo Rizzo ◽  
Bruno Sainz ◽  
Giuseppe Gigli ◽  
Loretta L. del Mercato ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Therapeutic Response ◽  
Three Dimensional ◽  
Cellular Models ◽  
Common Cancer ◽  
Cancer Models ◽  
Anti Cancer ◽  
Tumor Environment

Pancreatic cancer, the fourth most common cancer worldwide, shows a highly unsuccessful therapeutic response. In the last 10 years, neither important advancements nor new therapeutic strategies have significantly impacted patient survival, highlighting the need to pursue new avenues for drug development discovery and design. Advanced cellular models, resembling as much as possible the original in vivo tumor environment, may be more successful in predicting the efficacy of future anti-cancer candidates in clinical trials. In this review, we discuss novel bioengineered platforms for anticancer drug discovery in pancreatic cancer, from traditional two-dimensional models to innovative three-dimensional ones.

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