Identification of an Integrin α6‐Targeted Peptide for Nasopharyngeal Carcinoma‐Specific Nanotherapeutics

Feng, Guokai; Zhang, Mengqing; Wang, Hongxia; Cai, Jing; Chen, Shupeng; Wang, Qian; Gong, Jing; Leong, Kam W.; Wang, Jun; Zhang, Xing; Zeng, Mu‐Sheng

doi:10.1002/adtp.201900018

Cited by 20 publications

(26 citation statements)

References 43 publications

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“…Here, we confirmed that integrin α6 was overexpressed in human PDAC (Figure 1A,B) and increased integrin α6 had poorer prognosis for PDAC patients (Figure 1C). Recently, a peptide CRWYDENAC (dubbed RWY) targeting integrin α6 has been identified 8 and employed for nanotherapeutics of nasopharyngeal carcinoma 8 and for PET imaging of hepatocellular carcinoma by our team 9 . Here, we used the Ala scanning mutagenesis to modify the RWY peptide.…”

Section: Figurementioning

confidence: 99%

An optimized integrin α6‐targeted peptide for positron emission tomography/magnetic resonance imaging of pancreatic cancer and its precancerous lesion

Yan

Xiaochun

et al. 2020

Clinical & Translational Med

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An optimized integrin α6-targeted peptide for positron emission tomography/magnetic resonance imaging of pancreatic cancer and its precancerous lesion Dear Editor, Recently, we successfully developed a radiolabeled probe targeting integrin α6 for the positron emission tomography (PET)/magnetic resonance (MR) imaging of pancreatic ductal adenocarcinoma (PDAC) and its precancerous lesion, pancreatic intraepithelial neoplasia (PanIN). Most pancreatic cancers are PDAC. 1 Standard approaches for detecting PDAC at early stage are lacking with most diagnosed patients at advanced stage. 2 Tumortargeted molecular imaging significantly improved the tumor-detection rate, 3 which may also enhance the early diagnosis of PDAC. Considering the genetic complexity of PDAC, a PDAC-specific target with highly adaptability, sensitivity, and specificity is required. We selected integrin α6 as the target of PDAC as it was overexpressed in pancreatic cancer cells 4,5 and cancerous tissue of patients with PDAC 4,6,7 with an overexpression rate up to 92%. 4 Increased integrin α6 levels were associated with stronger PDAC cell invasiveness 5 and poorer prognosis for patients. 6,7 Furthermore, the integrin α6β4 dimer was overexpressed in PanIN even at a stage as early as PanIN 1A. 4 Here, we confirmed that integrin α6 was overexpressed in human PDAC (Figure 1A,B) and increased integrin α6 had poorer prognosis for PDAC patients (Figure 1C). Recently, a peptide CRWYDENAC (dubbed RWY) targeting integrin α6 has been identified 8 and employed for nanotherapeutics of nasopharyngeal carcinoma 8 and for PET imaging of hepatocellular carcinoma by our team. 9 Here, we used the Ala scanning mutagenesis to modify the RWY peptide. R, W, and Y were the three key amino acids within the RWY peptide, since their replacement by an alanine reduced the cellular binding ability of this peptide, both in vitro and in vivo. Interestingly, the alanine substitution of E resulted in the CRWYDANAC (dubbed S5) peptide with an approximately 1.5-fold enhanced tumor binding ability (Figure 1D,E). The This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Section: Figurementioning

confidence: 99%

An optimized integrin α6‐targeted peptide for positron emission tomography/magnetic resonance imaging of pancreatic cancer and its precancerous lesion

Yan

Xiaochun

et al. 2020

Clinical & Translational Med

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“…In our previous study, we screened out a peptide CRWYDDENAC (RWY) by phage display technology specific for nasopharyngeal carcinoma, and further identified that RWY was binding to integrin α6 which was highly expressed in multiple tumors. 25 Integrins, heterodimeric cell-face receptors composed of α and β subunits, are closely related to malignant biological behaviors in tumors including migration, invasion, metastasis and angiogenesis via mediating cell adhesion and signal transduction. [26][27][28][29] Integrin α6 subunit, encoded by ITGA6 gene in mammals, can be heterodimerized with either integrin β1 subunit or β4 subunit to form integrin α6β1 and α6β4, binding mostly and specifically to the extracellular matrix laminins.…”

Section: Introductionmentioning

confidence: 99%

An Optimized Integrin α6-Targeted Magnetic Resonance Probe for Molecular Imaging of Hepatocellular Carcinoma in Mice

Lin¹,

Zhang²,

Zhao³

et al. 2021

JHC

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Introduction: Integrin α6 is an attractive diagnostic biomarker for molecular imaging of hepatocellular carcinoma (HCC) as it has an extremely high positive rate (approximately 94%) in clinical early-stage HCC. In this study, based on our previously identified integrin α6-targeted peptide, we developed an optimized integrin α6-targeted magnetic resonance (MR) probe dubbed DOTA(Gd)-ANADYWR for MR imaging of HCC in mice. Materials and Methods: The longitudinal (R 1 ) relaxivity of DOTA(Gd)-ANADYWR was measured on a 3.0 T MR system . The specific tumor enhancement of the agent was investigated in four distinct mouse models, including subcutaneous, orthotopic, genetically engineered and chemically induced HCC mice. Results: The R 1 relaxivity value of DOTA(Gd)-ANADYWR is 5.11 mM −1 s −1 at 3.0 T, which is similar to that of the nonspecific clinical agent Gadoteridol. DOTA(Gd)-ANADYWR generated superior enhanced MR signal in HCC lesions and provided complementary enhancement MR signals to the clinically available hepatobiliary MR contrast agent gadoxetate disodium (Gd-EOB-DTPA). Importantly, DOTA(Gd)-ANADYWR could efficiently visualize small HCC lesion (approximately 1 mm) which was hardly detected by the clinical Gd-EOB-DTPA. Conclusion:These findings suggest the potential application of this integrin α6-targeted MR probe for the detection of HCC, particularly for small HCC.

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“…The treatment regime includes radiotherapy followed by cisplatin-loaded chemotherapy in case of advanced metastasis [12]. Surgery is generally avoided because of its sensitive area of occurrence [10,13]. However, the poor survival rate of nasopharyngeal carcinoma is an indication that there is a need to develop novel treatment therapies.…”

Section: Introductionmentioning

confidence: 99%

Investigating folate-conjugated combinatorial drug loaded ZnO nanoparticles for improved efficacy on nasopharyngeal carcinoma cell lines

Guo

Sun

2020

Journal of Experimental Nanoscience

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Zinc oxide (ZnO) nanoparticles, due to their well-defined physicochemical and antimicrobial attributes have been presented lately as favourable theranostic nanoplatforms for drug delivery. We hypothesized that surface modification of ZnO nanoparticle with activated polyethylene glycol and folic acid might be of great importance in targeted drug delivery in nasopharyngeal carcinoma since carcinoma cells possess folate receptors absent in normal cells. Therefore in this study, we have prepared and characterized activated PEG and folate conjugated dual drug loaded ZnO nanoparticles for increased cellular uptake efficiency in nasopharyngeal cancer cell lines. We synthesized the ZnO nanoparticles using sol-gel technique, conjugated them with activated PEG and folate and loaded them with two conventional anti-cancer drugs, namely cisplatin and docetaxel. The nanoparticle formulations were characterized by electron microscopy, stability studies, in-vitro release studies(acidic and normal pH), encapsulation & loading efficiency studies, FTIR and cytotoxicity studies. Additionally, cellline studies were done to assess cellular uptake efficiency using HNE-1 and CNE-2 cells. The dual drug loaded, folate & PEG activated ZnO nanoparticle were found to be extremely small size with high zeta potential & polydispersity index and high entrapment efficiency (82%) too. The nanoparticle formulations had stability and did not aggregate when kept in dispersed form for a long time. Moreover, they were found to be cytocompatible with negligible side-effects when incubated with normal cells. They also exhibited higher cellular uptake efficiencies when compared with free form. Therefore, it may safely concluded that combinatorial drug loaded, folate & PEG activated ZnO nanoparticle may result in better uptake of chemotherapeutic drugs with lower toxicity to normal cells.

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Identification of an Integrin α6‐Targeted Peptide for Nasopharyngeal Carcinoma‐Specific Nanotherapeutics

Cited by 20 publications

References 43 publications

An optimized integrin α6‐targeted peptide for positron emission tomography/magnetic resonance imaging of pancreatic cancer and its precancerous lesion

An optimized integrin α6‐targeted peptide for positron emission tomography/magnetic resonance imaging of pancreatic cancer and its precancerous lesion

An Optimized Integrin α6-Targeted Magnetic Resonance Probe for Molecular Imaging of Hepatocellular Carcinoma in Mice

Investigating folate-conjugated combinatorial drug loaded ZnO nanoparticles for improved efficacy on nasopharyngeal carcinoma cell lines

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