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

Tu, Yuanbiao; Ji, Tao; Wang, Fang; Liu, Peifei; Han, Zhihao; Li, Zhaolun; Ma, Yi; Gu, Yueqing

doi:10.1039/d0bm00162g

Cited by 19 publications

(18 citation statements)

References 34 publications

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“…For example, the peptide BBN 7-14 (Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH 2 ) composed of natural amino acids has a higher binding affinity with the CFPAC-1 cell line compared with the modified peptide GB-6 (Gln-5-Htp-β-Ala-Nva-Gln-His-NH 2 ) that consists of unnatural amino acids ( in vitro ). However, in vivo , BBN 7-14 has a reduced tumor-targeting ability compared with GB-6, which is stable against protease-mediate degradation and has a slightly lower uptake and slow metabolism ( 207 ). Currently, ACPs have been modified to improve specific cancer cell targets and enhance cancer cell elimination.…”

Section: Future Directionmentioning

confidence: 99%

Anticancer peptide: Physicochemical property, functional aspect and trend in clinical application (Review)

2020

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Cancer is currently ineffectively treated using therapeutic drugs, and is also able to resist drug action, resulting in increased side effects following drug treatment. A novel therapeutic strategy against cancer cells is the use of anticancer peptides (ACPs). The physicochemical properties, amino acid composition and the addition of chemical groups on the ACP sequence influences their conformation, net charge and orientation of the secondary structure, leading to an effect on targeting specificity and ACP-cell interaction, as well as peptide penetrating capability, stability and efficacy. ACPs have been developed from both naturally occurring and modified peptides by substituting neutral or anionic amino acid residues with cationic amino acid residues, or by adding a chemical group. The modified peptides lead to an increase in the effectiveness of cancer therapy. Due to this effectiveness, ACPs have recently been improved to form drugs and vaccines, which have sequentially been evaluated in various phases of clinical trials. The development of the ACPs remains focused on generating newly modified ACPs for clinical application in order to decrease the incidence of new cancer cases and decrease the mortality rate. The present review could further facilitate the design of ACPs and increase efficacious ACP therapy in the near future.

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Section: Future Directionmentioning

confidence: 99%

Anticancer peptide: Physicochemical property, functional aspect and trend in clinical application (Review)

2020

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“…To validate the results from the in vivo fluorescence imaging, we evaluated the capacity of radioactive conjugates for in vivo-targeted detection of HepG2 tumor using small animal SPECT-CT imaging. First, [ 99m Tc]Tc-HYNIC-PEG 4 -Ang II was radiolabeled with [ 99m Tc ]NaTcO 4 as previously described. , Details of [ 99m Tc]Tc-HYNIC-PEG 4 -Ang II are shown in Supporting Information. Radiochemical purity was >99%, with immediate specific activities >1.67 mCi/nmol after radiolabeling and a 18.7-min retention time for [ 99m Tc]Tc-HYNIC-PEG 4 -Ang II (Figure S21).…”

Section: Resultsmentioning

confidence: 99%

“…IHC and IF staining were performed as previously described . All snap-frozen biopsies were embedded by the OCT compound before sliced into 5 μm thickness and processed for further pathological analysis.…”

Section: Methodsmentioning

confidence: 99%

AT1R-Specific Ligand Angiotensin II as a Novel SPECT Agent for Hepatocellular Carcinoma Diagnosis

Liu

Wang

et al. 2020

ACS Sens.

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Hepatocellular carcinoma (HCC) is characterized by a high mortality and early diagnosis and treatment are critically needed. Ang II type 1 receptor (AT1R) has recently emerged as a potential molecular target for cancer diagnosis and intervention. Here, we labeled angiotensin II (Ang II), an AT1R ligand that is overexpressed in various solid cancers, with the near-infrared fluorescent dye, MPA, and radionuclide technetium-99m, and evaluated its capacity for HCC detection. These analyses were done in vitro using HepG2 (AT1R-positive) and BxPC3 (AT1R-negative) cell lines, and in vivo using a subcutaneous and orthotopic xenograft mouse model by fluorescence and SPECT imaging. Both Ang II-PEG4-MPA- and [99mTc]Tc-HYNIC-PEG4-Ang II-bound AT1R exhibited a high affinity in vitro and [99mTc]Tc-HYNIC-PEG4-Ang II displayed an acceptable level of in vitro stability in rat plasma and whole blood. In vivo imaging revealed excellent specific tumor-targeting in HepG2 mouse xenografts models. In vitro and in vivo competition experiments revealed specific Ang II-PEG4-MPA and [99mTc]Tc-HYNIC-PEG4-Ang II uptake by HepG2 cells and tumors. Altogether, AT1R-positive tumors were successfully detected via fluorescence and SPECT imaging using Ang II-PEG4-MPA and [99mTc]Tc-HYNIC-PEG4-Ang II, respectively. Given their superior targeting capacity, Ang II-PEG4-MPA and [99mTc]Tc-HYNIC-PEG4-Ang II are promising tools for HCC detection and warrant clinical translation.

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“…BBN could bind specifically to GRPR, which is overexpressed in a variety of tumor tissues and is associated with tumor infiltration and growth. 33 Flores et al found that GRPR was detected in 100% of the glioma samples analyzed, especially in the 24 cases of GBM. Highly expressed GRPR was also observed in tumor endothelial cells.…”

Section: Sensitivity and Specificitymentioning

confidence: 99%

“…growth 33. Flores et al found that GRPR was detected in 100% of the glioma samples analyzed, especially in the 24 cases of GBM.…”

mentioning

confidence: 99%

Resection and survival data from a clinical trial of glioblastoma multiforme‐specific IRDye800‐BBN fluorescence‐guided surgery

Chi

et al. 2020

Bioengineering & Transla Med

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Supra-maximum surgical tumor resection without neurological damage is highly valuable for treatment and prognosis of patients with glioblastoma multiforme (GBM). We developed a GBM-specific fluorescence probe using IRDye800CW (peak absorption/ emission, 778/795 nm) and bombesin (BBN), which (IRDye800-BBN) targets the gastrin-releasing peptide receptor, and evaluated the image-guided resection efficiency, sensitivity, specificity, and survivability. Twenty-nine patients with newly diagnosed GBM were enrolled. Sixteen hours preoperatively, IRDye800-BBN (1 mg in 20 ml sterile water) was intravenously administered. A customized fluorescence surgical navigation system was used intraoperatively. Postoperatively, enhanced magnetic resonance images were used to assess the residual tumor volume, calculate the resection extent, and confirm whether complete resection was achieved. Tumor tissues and nonfluorescent brain tissue in adjacent noneloquent boundary areas were harvested and assessed for diagnostic accuracy. Complete resection was achieved in 82.76% of patients. The median extent of resection was 100% (range, 90.6-100%). Eighty-nine samples were harvested, including 70 fluorescence-positive and 19 fluorescencenegative samples. The sensitivity and specificity of IRDye800-BBN were 94.44% (95% CI, 85.65-98.21%) and 88.24% (95% CI, 62.25-97.94%), respectively. Twenty-five Kunshan He, Chongwei Chi, Deling Li, and Jingjing Zhang authors contributed equally to this work.

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

Abstract: 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.

Cited by 19 publications

References 34 publications

Anticancer peptide: Physicochemical property, functional aspect and trend in clinical application (Review)

Anticancer peptide: Physicochemical property, functional aspect and trend in clinical application (Review)

AT1R-Specific Ligand Angiotensin II as a Novel SPECT Agent for Hepatocellular Carcinoma Diagnosis

Resection and survival data from a clinical trial of glioblastoma multiforme‐specific IRDye800‐BBN fluorescence‐guided surgery

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