MS1-type bioengineered spider silk nanoparticles do not exhibit toxicity in an in vivo mouse model

Nanomedicine ◽  
2021 ◽  
Author(s):  
Tomasz Deptuch ◽  
Anna Florczak ◽  
Anna Lewandowska ◽  
Ewa Leporowska ◽  
Karolina Penderecka ◽  
...  
Keyword(s):  
Spider Silk ◽  
Complete Blood Count ◽  
Growth Factor Receptor ◽  
Histopathological Analysis ◽  
Internal Organs ◽  
Toxicological Evaluation ◽  
Epidermal Growth ◽  
And Behavior ◽  
And Control

Background: Due to factors such as silk sequence, purification, degradation, morphology and functionalization, each silk variant should be individually tested for potential toxicity. Aim:   In vivo toxicological evaluation of the previously characterized bioengineered H2.1MS1 spider silk particles that can deliver chemotherapeutics to human epidermal growth factor receptor 2-positive breast cancer. Materials & methods: Silk nanoparticles (H2.1MS1 and control MS1) were administered intravenously to mice, and then the organismal response was assessed. Several parameters of acute and subchronic toxicity were analyzed, including animal mortality and behavior, nanosphere biodistribution, and histopathological analysis of internal organs. Also, the complete blood count, as well as the concentration of biochemical parameters and cytokines in the serum, were examined. Results & conclusion: No toxicity of the systemically administrated silk nanosphere was observed, indicating their potential application in biomedicine.

Toxicity and efficacy evaluation of multiple targeted polymalic acid conjugates for triple-negative breast cancer treatment

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Triple Negative ◽  
Growth Factor Receptor ◽  
Engineered Nanoparticles ◽  
Efficacy Evaluation ◽  
Dual Action ◽  
Epidermal Growth ◽  
Laminin 411 ◽  
Immunologic Analysis

Engineered nanoparticles are widely used for delivery of drugs but frequently lack proof of safetyfor cancer patient's treatment. All-in-one covalent nanodrugs of the third generation have beensynthesized based on a poly(β-L-malic acid) (PMLA) platform, targeting human triple-negativebreast cancer (TNBC). They significantly inhibited tumor growth in nude mice by blockingsynthesis of epidermal growth factor receptor, and α4 and β1 chains of laminin-411, the tumorvascular wall protein and angiogenesis marker. PMLA and nanodrug biocompatibility and toxicityat low and high dosages were evaluated in vitro and in vivo. The dual-action nanodrug and singleactionprecursor nanoconjugates were assessed under in vitro conditions and in vivo with multipletreatment regimens (6 and 12 treatments). The monitoring of TNBC treatment in vivo withdifferent drugs included blood hematologic and immunologic analysis after multiple intravenousadministrations. The present study demonstrates that the dual-action nanoconju-gate is highlyeffective in preclinical TNBC treatment without side effects, supported by hematologic andimmunologic assays data. PMLA-based nanodrugs of the Polycefin™ family passed multipletoxicity and efficacy tests in vitro and in vivo on preclinical level and may prove to be optimizedand efficacious for the treatment of cancer patients in the future.

scholarly journals Imaging-Guided Therapy Simultaneously Targeting HER2 and EpCAM with Trastuzumab and EpCAM-Directed Toxin Provides Additive Effect in Ovarian Cancer Model

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3939
Author(s):  
Tianqi Xu ◽  
Anzhelika Vorobyeva ◽  
Alexey Schulga ◽  
Elena Konovalova ◽  
Olga Vorontsova ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Growth Factor Receptor ◽  
Repeated Administration ◽  
Ovarian Cancer Cells ◽  
Her2 Positive ◽  
Efficient Treatment ◽  
Pseudomonas Exotoxin A ◽  
Epidermal Growth

Efficient treatment of disseminated ovarian cancer (OC) is challenging due to its heterogeneity and chemoresistance. Overexpression of human epidermal growth factor receptor 2 (HER2) and epithelial cell adhesion molecule (EpCAM) in approx. 30% and 70% of ovarian cancers, respectively, allows for co-targeted treatment. The clinical efficacy of the monoclonal antibody trastuzumab in patients with HER2-positive breast, gastric and gastroesophageal cancers makes it readily available as the HER2-targeting component. As the EpCAM-targeting component, we investigated the designed ankyrin repeat protein (DARPin) Ec1 fused to a truncated variant of Pseudomonas exotoxin A with reduced immunogenicity and low general toxicity (LoPE). Ec1-LoPE was radiolabeled, evaluated in ovarian cancer cells in vitro and its biodistribution and tumor-targeting properties were studied in vivo. The therapeutic efficacy of Ec1-LoPE alone and in combination with trastuzumab was studied in mice bearing EpCAM- and HER2-expressing SKOV3 xenografts. SPECT/CT imaging enabled visualization of EpCAM and HER2 expression in the tumors. Co-treatment using Ec1-LoPE and trastuzumab was more effective at reducing tumor growth and prolonged the median survival of mice compared with mice in the control and monotherapy groups. Repeated administration of Ec1-LoPE was well tolerated without signs of hepatic or kidney toxicity. Co-treatment with trastuzumab and Ec1-LoPE might be a potential therapeutic strategy for HER2- and EpCAM-positive OC.

scholarly journals Epidermal growth factor receptor kinase translocation and activation in vivo.

1986 ◽  
Vol 261 (18) ◽  
pp. 8473-8480
Author(s):  
D G Kay ◽  
W H Lai ◽  
M Uchihashi ◽  
M N Khan ◽  
B I Posner ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Receptor Kinase ◽  
Epidermal Growth

scholarly journals Biodistribution and Tumor Uptake of 67Ga-Nimotuzumab in a Malignant Pleural Mesothelioma Xenograft

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3138 ◽  
Author(s):  
Vanessa Izquierdo-Sánchez ◽  
Saé Muñiz-Hernández ◽  
Héctor Vázquez-Becerra ◽  
Judith Pacheco-Yepez ◽  
Mario Romero-Piña ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Malignant Pleural Mesothelioma ◽  
Growth Factor Receptor ◽  
In Vivo Studies ◽  
Pleural Mesothelioma ◽  
Tumor Uptake ◽  
Epidermal Growth ◽  
Significant Uptake

Malignant pleural mesothelioma (MPM) is the most common tumor of the pulmonary pleura. It is a rare and aggressive malignancy, generally associated with continuous occupational exposure to asbestos. Only a multimodal-approach to treatment, based on surgical resection, chemotherapy and/or radiation, has shown some benefits. However, the survival rate remains low. Nimotuzumab (h-R3), an anti-EGFR (epidermal growth factor receptor) humanized antibody, is proposed as a promising agent for the treatment of MPM. The aim of this research was to implement a procedure for nimotuzumab radiolabeling to evaluate its biodistribution and affinity for EGF (epidermal growth factor) receptors present in a mesothelioma xenograft. Nimotuzumab was radiolabeled with 67Ga; radiolabel efficiency, radiochemical purity, serum stability, and biodistribution were evaluated. Biodistribution and tumor uptake imaging studies by microSPECT/CT in mesothelioma xenografts revealed constant nimotuzumab uptake at the tumor site during the first 48 h after drug administration. In vivo studies using MPM xenografts showed a significant uptake of this radioimmunoconjugate, which illustrates its potential as a biomarker that could promote its theranostic use in patients with MPM.

scholarly journals Tc-99m direct radiolabeling of monoclonal antibody ior egf/r3: quality control and image studies in mice

2005 ◽  
Vol 48 (spe2) ◽  
pp. 29-35 ◽  
Author(s):  
Carla Roberta Dias ◽  
Barbara Marczewski ◽  
Vanessa Moraes ◽  
Marycel Figols de Barboza ◽  
João Alberto Osso Junior
Keyword(s):  
Monoclonal Antibody ◽  
Nuclear Medicine ◽  
Growth Factor Receptor ◽  
Lyophilized Formulation ◽  
Epithelial Origin ◽  
Epidermal Growth ◽  
High Yields ◽  
Efficiency Effects

Monoclonal antibodies (Mabs) have been useful for immunoscintigraphic applications in clinical diagnosis since they were introduced in the practice of nuclear medicine. The ior egf/r3 (Centis, Cuba) is a murine monoclonal antibody against epidermal growth factor receptor (EGF-R) and has been widely used in the radioimmunodiagnosis of tumors of epithelial origin. Labeled with 99mTc, its main application in Nuclear Medicine is the follow up, detection and evaluation of tumor recurrences. The objective of this work is to describe the preparation of a lyophilized formulation (kit) for radiolabeling the Mab ior egf/r3 with 99mTc for immunoscintigraphic applications. Radiolabeling efficiency, effects on immunoreactivity, image studies and stability of the formulation are reported. The study demonstrated that the kit formulation can be labeled with 99mTc at high yields and can be used to visualize in vivo human tumors of epithelial origin by immunoscintigraphy studies.

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