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 ◽  
...  

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.

Author(s):  
Li Li ◽  
Mi Yang ◽  
Rutian Li ◽  
Jing Hu ◽  
Lixia Yu ◽  
...  

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.


2020 ◽  
Vol 8 (9) ◽  
pp. 2682-2693 ◽  
Author(s):  
Yuanbiao Tu ◽  
Ji Tao ◽  
Fang Wang ◽  
Peifei Liu ◽  
Zhihao Han ◽  
...  

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.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jae Do Yoo ◽  
Sang Mun Bae ◽  
Junyoung Seo ◽  
In Seon Jeon ◽  
Sri Murugan Poongkavithai Vadevoo ◽  
...  

AbstractTRAIL is considered a promising target for cancer therapy because it mediates activation of the extrinsic apoptosis pathway in a tumor-specific manner by binding to and trimerizing its functional receptors, DR4 or DR5. Although recombinant human TRAIL has shown high potency and specificity for killing cancer cells in preclinical studies, it has failed in multiple clinical trials for several reasons, including a very short half-life mainly caused by instability of the monomeric form of TRAIL and rapid renal clearance of the off-targeted TRAIL. To overcome such obstacles, we developed a TRAIL-active trimer nanocage (TRAIL-ATNC) that presents the TRAIL ligand in its trimer-like conformation by connecting it to a triple helix sequence that links to the threefold axis of the ferritin nanocage. We also ligated the tumor-targeting peptide, IL4rP, to TRAIL-ATNC to enhance tumor targeting. The developed TRAIL-ATNCIL4rP showed enhanced agonistic activity compared with monomeric TRAIL. The in vivo serum half-life of TRAIL-ATNCIL4rP was ~ 16-times longer than that of native TRAIL. As a consequence of these properties, TRAIL-ATNCIL4rP exhibited efficacy as an anti-tumor agent in vivo against xenograft breast cancer as well as orthotopic pancreatic cancer models, highlighting the promise of this system for development as novel therapeutics against cancer.


2020 ◽  
Vol 8 (8) ◽  
pp. 2274-2282 ◽  
Author(s):  
Yue Cai ◽  
Zhuomin Xu ◽  
Qi Shuai ◽  
Fangtao Zhu ◽  
Jiao Xu ◽  
...  

PEG-PLA micelles are modified with F3 peptides, thus endowing the micelles with active-targeting ability due to the nucleolin-binding ability of the F3 peptides.


2021 ◽  
Vol 12 ◽  
Author(s):  
Guoliang Liu ◽  
Min Wang ◽  
Hongyu He ◽  
Jiannan Li

Colorectal cancer is the third most common malignant disease worldwide, and chemotherapy has been the standard treatment for colorectal cancer. However, the therapeutic effects of chemotherapy are unsatisfactory for advanced and recurrent colorectal cancers. Thus, increasing the treatment efficacy of chemotherapy in colorectal cancer is a must. In this study, doxorubicin (DOX)-loaded tumor-targeting peptide-decorated mPEG-P(Phe-co-Cys) nanoparticles were developed to treat orthotopic colon cancer in mice. The peptide VATANST (STP) can specifically bind with vimentin highly expressed on the surface of colon cancer cells, thus achieving the tumor-targeting effects. The nanoparticles are core-shell structured, which can protect the loaded DOX while passing through the blood flow and increase the circulation time. The disulfide bonds within the nanoparticles are sensitive to the glutathione-rich microenvironment of tumor tissues. Rupture of disulfide bonds of the nanoparticles leads to the continuous release of DOX, thus resulting in the apoptosis of the tumor cells. The in vivo experiments in mice with orthotopic colon cancer demonstrated that the synthesized DOX-loaded tumor-targeting peptide-decorated polypeptide nanoparticles showed properties of drug delivery systems and exhibited good antitumor properties. The synthesized nanoparticles show appropriate properties as one of the drug delivery systems and exhibit good antitumor properties after encapsulating DOX.


2021 ◽  
Author(s):  
Janice Miller ◽  
Yasuko Maeda ◽  
Stephanie Au ◽  
Frances Gunn ◽  
Lorna Porteous ◽  
...  

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C.C Van 't Klooster ◽  
P.M Ridker ◽  
N.R Cook ◽  
J.G.J.V Aerts ◽  
J Westerink ◽  
...  

Abstract Background As treatment for cardiovascular disease (CVD) has improved substantially over the last decades, more patients survive acute CVD manifestations and are at risk for developing cancer as well as recurrent CVD. Due to similar risk factors, including smoking and obesity, patients with established CVD are at higher risk for cancer. Objectives The aim of this study was to develop and externally validate prediction models for the estimation of 10-year and lifetime risk for total, colorectal, and lung cancer in patients with established CVD. Methods Data from patients with established CVD from the UCC-SMART prospective cohort study (N=7,280) were used for model development, and data from the CANTOS trial (N=9,322) were used for model validation. Predictors were selected based on previously published cancer risk prediction models or cancer risk factors, easy clinical availability, and availability in the derivation dataset (UCC-SMART cohort). A Fine and Gray competing risk-adjusted lifetime model was developed for total, colorectal, and lung cancer. Results Selected predictors were age, sex, smoking status, weight, height, alcohol use, antiplatelet use, diabetes mellitus, and C-reactive protein. External calibration for 4-year risks of the total cancer, colorectal cancer, and lung cancer models was good (Figure 1), and C-statistics were 0.63–0.74 in the CANTOS trial population. Median predicted lifetime risks in CANTOS were 26% (range 1%-52%) for total cancer, 4% (range 0%-13%) for colorectal cancer, and 5% (range 0%-37%) for lung cancer. Conclusions Lifetime and 10-year risk of cancer can be estimated with easy to measure variables in patients with established CVD, showing a wide distribution of predicted lifetime risks for total cancer and lung cancer. Using these lifetime models in clinical practice could increase understanding of cancer risk and aid in emphasizing healthy lifestyle changes. Figure 1. Calibration plots of cancer models Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): University Medical Center; Additional funding: CANTOS trial was funded by Novartis Pharmaceuticals.


BioMetals ◽  
2021 ◽  
Author(s):  
Alessio Menconi ◽  
Tiziano Marzo ◽  
Lara Massai ◽  
Alessandro Pratesi ◽  
Mirko Severi ◽  
...  

AbstractChloro(triethylphosphine)gold(I), (Et3PAuCl hereafter), is an Auranofin (AF)-related compound showing very similar biological and pharmacological properties. Like AF, Et3PAuCl exhibits potent antiproliferative properties in vitro toward a variety of cancer cell lines and is a promising anticancer drug candidate. We wondered whether Et3PAuCl encapsulation might lead to an improved pharmacological profile also considering the likely reduction of unwanted side-reactions that are responsible for adverse effects and for drug inactivation. Et3PAuCl was encapsulated in biocompatible PLGA–PEG nanoparticles (NPs) and the new formulation evaluated in colorectal HCT-116 cancer cells in comparison to the free gold complex. Notably, encapsulated Et3PAuCl (nano-Et3PAuCl hereafter) mostly retains the cellular properties of the free gold complex and elicits even greater cytotoxic effects in colorectal cancer (CRC) cells, mediated by apoptosis and autophagy. Moreover, a remarkable inhibition of two crucial signaling pathways, i.e. ERK and AKT, by nano-Et3PAuCl, was clearly documented. The implications of these findings are discussed.


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