Targeted cancer therapy through antibody fragments-decorated nanomedicines

Alibakhshi, Abbas; Kahaki, Fatemeh Abarghooi; Ahangarzadeh, Shahrzad; Yaghoobi, Hajar; Yarian, Fatemeh; Arezumand, Roghaye; Ranjbari, Javad; Mokhtarzadeh, Ahad; Guárdia, Miguel de la

doi:10.1016/j.jconrel.2017.10.036

Cited by 144 publications

(84 citation statements)

References 132 publications

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“…An important benefit of these approaches is that nanocarriers can be internalized by MDR cells via non-specific endocytosis, resulting in higher intracellular accumulation of the drug. To enhance tumor targeting, the nanovector surface is usually modified with a ligand [9] or antibody [10]. Aptamers identified by an in vitro selection procedure known as systematic evolution of ligands by exponential enrichment (SELEX) have broad medical applications as drug delivery ligands due to their low immunogenicity and toxicity, high binding affinity, specificity, and wide range of targets [11,12].…”

Section: Introductionmentioning

confidence: 99%

Overcoming Drug Resistance in Colon Cancer by Aptamer-Mediated Targeted Co-Delivery of Drug and siRNA Using Grapefruit-Derived Nanovectors

Yan

Tao

Jiang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Multidrug resistance (MDR) is the most common cause of chemotherapy failure. Upregulation of P-glycoprotein (P-gp) is one of the main mechanisms underlying MDR. Methods: In this study, we developed a targeted drug and small interfering (si)RNA co-delivery system based on specific aptamer-conjugated grapefruit-derived nanovectors (GNVs) that we tested in MDR LoVo colon cancer cells. The internalization of nanovectors in cancer cells was tested by fluorescence microscopy and flow cytometry. The anti-cancer activity in vitro was determined by colony formation and cell apoptosis assays. The biodistribution of nanovectors was analyzed by live imaging and the anti-cancer activity in vivo was observed. Results: GNVs loaded with aptamer increased doxorubicin (Dox) accumulation in MDR LoVo cells, an effect that was abolished by pretreatment with DNase. The LA1 aptamer effectively promoted nanovector internalization into cells at 4°C and increased the targeted delivery of Dox to tumors. Constructs harboring Dox, LA1, and P-gp siRNA more effectively inhibited proliferation and enhanced apoptosis in cultured MDR LoVo cells while exhibiting more potent anti-tumor activity in vivo than free Dox or GNVs loaded with Dox alone or in conjunction with LA1, an effect that was associated with downregulation of P-gp expression. Conclusion: This GNV-based system may be an effective strategy for overcoming MDR in clinical settings.

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Section: Introductionmentioning

confidence: 99%

Overcoming Drug Resistance in Colon Cancer by Aptamer-Mediated Targeted Co-Delivery of Drug and siRNA Using Grapefruit-Derived Nanovectors

Yan

Tao

Jiang

et al. 2018

Cell Physiol Biochem

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“…Fab' fragments have better tissue penetration, are not susceptible to Fc-mediated uptake and do not exert immune effector functions. Therefore, Fab' fragments have been used for treatment of certain autoimmune diseases (15), targeting of different payloads (16,17), and generation of bispecific antibodies (18). The conventional method to obtain Fab' fragments is papain cleavage of the parental mAb followed by purification of the Fab' fragment.…”

Section: Generation Of Recombinant Hybridomas Producing Sortagable Famentioning

confidence: 99%

Functional diversification of hybridoma produced antibodies by CRISPR/HDR genomic engineering

Schoot

Fennemann

Valente

et al. 2019

Preprint

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These authors jointly supervised this work and are corresponding authors. Email: Martijn.Verdoes@radboudumc.nl (M.V.); f.a.scheeren@lumc.nl (F.A.S.). One Sentence Summary:We demonstrate a universal CRISPR/HDR based platform for rapid genetic engineering of hybridomas to obtain functionally diverse antibody isotype panels in the species and format of choice. Abstract:Hybridoma technology is instrumental for the development of novel antibody therapeutics and diagnostics. Recent preclinical and clinical studies highlight the importance of antibody isotype for therapeutic efficacy. However, since the sequence encoding the constant domains is fixed, tuning antibody function in hybridomas has been restricted. Here, we demonstrate a versatile CRISPR/HDR platform to rapidly engineer the constant immunoglobulin domains to obtain recombinant hybridomas which secrete antibodies in the preferred format, species and isotype. Using this platform, we obtained recombinant hybridomas secreting Fab' fragments, isotype switched chimeric antibodies, and Fc-silent mutants. These antibody products are stable, retain their antigen specificity, and display their intrinsic Fc-effector functions in vitro and in vivo. Furthermore, we can site-specifically attach cargo to these antibody products via chemo-enzymatic modification. We believe this versatile platform facilitates antibody engineering for the entire scientific community, empowering preclinical antibody research.

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“…For instance, the combination of nanoparticles with antibodies introduces maximum advantages with higher safety and selectivity than each carrier alone ( fig. 5) [47][48][49][50]. This combination depends on the capability of nanoparticles to carry a large number of toxic drugs and the ability of antibodies to provide these drugs specifically into the site of action through the endocytosis mechanism [47].…”

Section: Fig 5: a Combination Of Nanoparticle With Antibodies And Otmentioning

confidence: 99%

The Impact of New Targeting Methods in the Cancer Therapy

2019

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Rapid development has achieved in treating tumor to stop malignant cell growth and metastasis in the past decade. Numerous researches have emerged to increase potency and efficacy with novel methods for drug delivery. The main objective of this literature review was to illustrate the impact of current new targeting methods to other previous delivering systems to select the most appropriate method in cancer therapy. This review first gave a brief summary of cancer structure and highlighted the main roles of targeting systems. Different types of delivering systems have been addressed in this literature review with focusing on the latest carrier derived from malarial protein. The remarkable advantages and main limitations of the later have been also discussed. PubMed and Science Direct were the main search engines that have been used as information sources to prepare this review. Articles related to cancer targeting system, active and passive processes, current nanoparticles, antibody carriers, and current novel cancer carriers were used as sources in this review. Important points from many references published in the last decade (2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017)(2018) were selected and included. Several targeting methods were introduced to enhance the efficacy and tolerability of the toxic drug by active and passive processes, but there is still no conclusive carrier without certain drawbacks. A combination of targeting methods probably shows the most appropriate choice for increasing selectivity and safety of anticancer drugs via reducing the concentration of carriers used. I In nt te er rn na at ti io on na al l J Jo ou ur rn na al l o of f A Ap pp pl li ie ed d P Ph ha ar rm ma ac ce eu ut ti ic cs s

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Targeted cancer therapy through antibody fragments-decorated nanomedicines

Cited by 144 publications

References 132 publications

Overcoming Drug Resistance in Colon Cancer by Aptamer-Mediated Targeted Co-Delivery of Drug and siRNA Using Grapefruit-Derived Nanovectors

Overcoming Drug Resistance in Colon Cancer by Aptamer-Mediated Targeted Co-Delivery of Drug and siRNA Using Grapefruit-Derived Nanovectors

Functional diversification of hybridoma produced antibodies by CRISPR/HDR genomic engineering

The Impact of New Targeting Methods in the Cancer Therapy

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