Alireza Khabiri, Banafsheh Rastegari, Gholamreza Rafiei Dehbidi, Amir Savardashtaki, Mohammad Ali Takhshid
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引用次数: 0
Abstract
Aims: This study aimed to develop a targeted drug delivery system based on anti-CD22 single-chain variable fragment (ScFv) conjugated to β-cyclodextrin (β-CD) Bio-MOFs for the selective delivery of daunorubicin (DNR) to CD22-positive B-cell tumor cells.
Materials and methods: The anti-CD22-ScFv gene was designed using the variable heavy (VH) and light (VL) chain regions of the human RFB4 antibody and cloned into the pET28a vector, followed by expression in E.coli BL21 (DE3). The recombinant protein was purified by affinity chromatography and confirmed by SDS-PAGE. Anti-CD22-ScFv-β-CD Bio-MOFs were synthesized using glutaraldehyde and L-lysine as crosslinkers and subsequently loaded with DNR. The formation of the nanostructure was verified by ATR-FTIR spectroscopy and zeta potential analysis. Drug uptake and cytotoxic effects were evaluated in CD22-positive Raji cells and CD22-negative Jurkat cells using fluorescence microscopy, flow cytometry, and the MTT assay.
Results: Successful expression and purification of anti-CD22-ScFv were confirmed by SDS-PAGE. Characterization analyses verified the formation of anti-CD22-ScFv-β-CD-DNR Bio-MOFs. The targeted system facilitated efficient uptake of DNR in CD22-positive Raji cells and induced significant dose-dependent cytotoxicity. In contrast, minimal effects were observed in CD22-negative Jurkat cells.
Conclusions: Anti-CD22-ScFv-β-CD-DNR Bio-MOFs demonstrate effective and selective delivery of DNR to CD22-expressing cells and may represent a promising targeted therapeutic approach for B-cell malignancies.
期刊介绍：
Delivering therapeutics in a way that is right for the patient - safe, painless, reliable, targeted, efficient and cost effective - is the fundamental aim of scientists working in this area. Correspondingly, this evolving field has already yielded a diversity of delivery methods, including injectors, controlled release formulations, drug eluting implants and transdermal patches. Rapid technological advances and the desire to improve the efficacy and safety profile of existing medications by specific targeting to the site of action, combined with the drive to improve patient compliance, continue to fuel rapid research progress. Furthermore, the emergence of cell-based therapeutics and biopharmaceuticals such as proteins, peptides and nucleotides presents scientists with new and exciting challenges for the application of therapeutic delivery science and technology. Successful delivery strategies increasingly rely upon collaboration across a diversity of fields, including biology, chemistry, pharmacology, nanotechnology, physiology, materials science and engineering. Therapeutic Delivery recognizes the importance of this diverse research platform and encourages the publication of articles that reflect the highly interdisciplinary nature of the field. In a highly competitive industry, Therapeutic Delivery provides the busy researcher with a forum for the rapid publication of original research and critical reviews of all the latest relevant and significant developments, and focuses on how the technological, pharmacological, clinical and physiological aspects come together to successfully deliver modern therapeutics to patients. The journal delivers this essential information in concise, at-a-glance article formats that are readily accessible to the full spectrum of therapeutic delivery researchers.
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