Single chain variable fragment fused to maltose binding protein: a modular nanocarrier platform for the targeted delivery of antitumorals

Reche-Perez, Francisco J; Plesselova, Simona; Reyes-Berbel, Eduardo De Los; Ortega‐Muñoz, Mariano; Lopéz-Jaramillo, Javier; Hernández-Matéo, Fernando; Santoyo‐González, Francisco; Salto, Rafael; Girón, María D.

doi:10.1039/d0bm01903h

Cited by 4 publications

(3 citation statements)

References 57 publications

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“…A co-expression system was used to produce a soluble fusion MBP-D16F7 scFv in E. coli. The scFv fragment was developed as a fusion protein MBP-scFv, which not only provides a more soluble and functional protein, but also can bind the scFv to the maltose on the surface of BioMOFs (Ca-Gly-Maltose) ( Reche-Perez et al, 2021 ). Our results showed that the synthesized BioMOFs were safe and nontoxic as empty carriers and that the unloaded Ca-Gly-D16F7 BioMOF had a stronger effect on cancer cells than on normal cells by inhibiting the proliferation of eukaryotic cells especially at a concentration greater than 100 μg/ml ( Supplementary Figure S2 ).…”

Section: Discussionmentioning

confidence: 99%

Targeted Codelivery of Prodigiosin and Simvastatin Using Smart BioMOF: Functionalization by Recombinant Anti-VEGFR1 scFv

Mirzaeinia

Zeinali

Budiša

et al. 2022

Front. Bioeng. Biotechnol.

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Biological metal-organic frameworks (BioMOFs) are hybrid compounds in which metal nodes are linked to biocompatible organic ligands and have potential for medical application. Herein, we developed a novel BioMOF modified with an anti-VEGFR1 scFv antibody (D16F7 scFv). Our BioMOF is co-loaded with a combination of an anticancer compound and a lipid-lowering drug to simultaneously suppress the proliferation, growth rate and metastases of cancer cells in cell culture model system. In particular, Prodigiosin (PG) and Simvastatin (SIM) were co-loaded into the newly synthesized Ca-Gly BioMOF nanoparticles coated with maltose and functionalized with a recombinant maltose binding protein-scFv fragment of anti-VEGFR1 (Ca-Gly-Maltose-D16F7). The nanoformulation, termed PG + SIM-NP-D16F7, has been shown to have strong active targeting behavior towards VEGFR1-overexpresing cancer cells. Moreover, the co-delivery of PG and SIM not only effectively inhibits the proliferation of cancer cells, but also prevents their invasion and metastasis. The PG + SIM-NP-D16F7 nanocarrier exhibited stronger cytotoxic and anti-metastatic effects compared to mono-treatment of free drugs and drug-loaded nanoparticles. Smart co-delivery of PG and SIM on BioMOF nanoparticles had synergistic effects on growth inhibition and prevented cancer cell metastasis. The present nanoplatform can be introduced as a promising tool for chemotherapy compared with mono-treatment and/or non-targeted formulations.

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Section: Discussionmentioning

confidence: 99%

Targeted Codelivery of Prodigiosin and Simvastatin Using Smart BioMOF: Functionalization by Recombinant Anti-VEGFR1 scFv

Mirzaeinia

Zeinali

Budiša

et al. 2022

Front. Bioeng. Biotechnol.

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“…Among existing expression systems, those based on E. coli have become popular for use in scFvs preparation, although use of an E. coli -based system to generate the two intrachain disulfide bonds necessary for antibody folding and antigen-binding activity can be challenging [ 20 ]. To address this problem, researchers have designed various strategies to produce functional scFvs by promoting their accumulation within the periplasm, where the oxidising environment supports disulfide bond formation and corrects scFv folding [ 20 , 37 , 42 – 45 ]. In this work, AK2 was expressed in soluble form in E. coli HB2151 cells after it was isolated from the scFv phage library.…”

Section: Discussionmentioning

confidence: 99%

Expression, purification and characterisation of a human anti-CDK4 single-chain variable fragment antibody

Zhao

Yang

et al. 2021

BMC Biotechnol

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Background Cyclin-dependent kinase 4 (CDK4) when hyperactivated drives development and maintenance of most tumour types, thus prompting its use as an essential cancer treatment target and a diagnostic tool. Target-binding molecules, such as single-chain variable fragment (scFv) antibodies, hold tremendous potential for use in a wide range of cancer diagnostic and therapeutic applications. Results A human anti-CDK4 scFv antibody (AK2) derived from a human phage display library was expressed in soluble form in Escherichia coli and shown to be secreted into the culture supernatant. Next, soluble AK2 within culture supernatant was successfully purified using affinity chromatography then was shown, using enzyme-linked immunosorbent assays, to bind to recombinant human CDK4 with high affinity and specificity. Further analyses of AK2 interactions with intracellular components demonstrated that AK2 recognised and interacted specifically with endogenous CDK4 and thus could be useful for detection of CDK4 within tumour cells. Conclusions A novel anti-CDK4 scFv antibody that can recognise and interact specifically with recombinant human CDK4 and endogenous CDK4 in tumour cells was expressed and purified successfully. These results suggest that the anti-CDK4 scFv antibody may serve as a new and promising tool for achieving CDK4-targeted diagnosis, prognosis and treatment of numerous types of cancers.

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“…Despite having several advantages (e.g., high affinity and specificity toward their pertinent antigens), full-length antibodies are relatively large molecules (ranging 140-150 kDa). This drawback may limit their application when dealing with solid tumors [28, 29]. Long half-life and limited penetration of full-length antibodies can lead to high background levels, resulting in a low tumor-to-background ratio [3, 30].…”

Section: Introductionmentioning

confidence: 99%

Near-Infrared Fluorescence Imaging of EGFR-Overexpressing Tumors in the Mouse Xenograft Model Using scFv-IRDye800CW and Cetuximab-IRDye800CW

2022

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EGFR (epidermal growth factor receptor) is overexpressed in a variety of human cancers (including squamous cell carcinoma of head and neck, colon cancer, and some breast cancers) and therefore is regarded as an ideal target for cancer therapy or imaging purposes. In the current study, we produced a scFv-based near-infrared probe (called cet.Hum.scFv-IRDye-800CW) and evaluated its ability in recognizing and imaging of EGFR-overexpressing tumors in a mouse model. Like the molecular probe consisting of its parental antibody (cetuximab, an FDA-approved monoclonal antibody) and IRD800CW, cet.Hum.scFv-IRDye-800CW was able to recognize EGFR-overexpressing tumors in mice. cet.Hum.scFv-IRDye-800CW was found to be superior to the cetuximab-based probe in imaging of mouse tumors. The tumor-to-background ratio and blood clearance rate were higher when cet.Hum.scFv-IRDye-800CW was used as an imaging probe.

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Single chain variable fragment fused to maltose binding protein: a modular nanocarrier platform for the targeted delivery of antitumorals

Abstract: A modular platform for targeted delivery was based on a single chain variable (ScFv) fragment fused to maltose-binding protein (MBP). Using different maltosylated ligands it is likely to target, transport drugs, or deliver genes to specific cells.

Cited by 4 publications

References 57 publications

Targeted Codelivery of Prodigiosin and Simvastatin Using Smart BioMOF: Functionalization by Recombinant Anti-VEGFR1 scFv

Targeted Codelivery of Prodigiosin and Simvastatin Using Smart BioMOF: Functionalization by Recombinant Anti-VEGFR1 scFv

Expression, purification and characterisation of a human anti-CDK4 single-chain variable fragment antibody

Near-Infrared Fluorescence Imaging of EGFR-Overexpressing Tumors in the Mouse Xenograft Model Using scFv-IRDye800CW and Cetuximab-IRDye800CW

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