Efficient and High-Speed Transduction of an Antibody into Living Cells Using a Multifunctional Nanocarrier System to Control Intracellular Trafficking

Yamada, Yuma; Perez, Sandra Milena Vergara; Tabata, Mai; Abe, Jiro; Yasuzaki, Yukari; Harashima, Hideyoshi

doi:10.1002/jps.24310

Cited by 20 publications

(16 citation statements)

References 41 publications

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“…4). The surfactant (DOC) molecules released from DOC-LS into the cell membrane perturb the normal liquid crystal state of the bilayer membrane, leading to unsteadiness of the cytomembrane, and an increase in its permeability, which consequently favoured the cellular entry and endosomal escape of the prepared nanovesicles, allowing them to deliver drugs to the cytoplasm [23]. The smaller particle size may also play any role in the better internalisation of DOC-LS than that of the conventional LS.…”

Section: Resultsmentioning

confidence: 99%

DOC‐LS, a new liposome for dermal delivery, and its endocytosis by HaCaT and CCC‐ESF‐1 cells

Zhang

et al. 2018

IET nanobiotechnol.

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The main objective of this work was to investigate the uptake channels of skin cells through which coumarin 6, transported by deoxycholate-mediated liposomes (DOC-LS), was internalised; this was also compared against the action of conventional LS. Coumarin 6-loaded DOC-LS and LS were characterised for size distribution, zeta potential, and shape, and analysed in vitro in human epidermal immortal keratinocyte (HaCaT) (epidermal) and human embryonic skin fibroblast (CCC-ESF-1) (dermal) cell lines. Various endocytosis inhibitors were incubated with cells treated with the nanocarriers. Flow cytometry results indicated that HaCaT and CCC-ESF-1 cells internalise the tested preparations through pinocytotic vesicles, macropinocytosis, clathrin-mediated endocytic pathways, and via lysosomes, which consume a considerable amount of energy. The endocytosis pathways of DOC-LS and LS showed no difference. This study provides a basis for the application of LS being combined with a microneedle system for efficient intracellular drug delivery, targeting cutaneous histocyte disorders.

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Section: Resultsmentioning

confidence: 99%

DOC‐LS, a new liposome for dermal delivery, and its endocytosis by HaCaT and CCC‐ESF‐1 cells

Zhang

et al. 2018

IET nanobiotechnol.

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“…In addition, the results of the immunofluorescence assay determined that the hMTH1 mAb purified from ascites had specific binding capacity to the natural hMTH1 expressed on the human breast cell line MCF-7. Though hMTH1 is a cytoplasmic protein, various methods have been reported to transduce antibodies into cells (24)(25)(26)(27). MTH1 is a non-essential enzyme in normal cells that is overexpressed in tumours, so its antibodies could play a role in targeted therapy for the broad-spectrum treatment of cancers.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, generating therapeutic mAbs that recognise intracellular tumour antigens will facilitate possible cancer target selection and enhance therapeutic potency. Various efficient and safe methods of delivering an antibody into a living cell have been introduced, such as cell-penetrating peptides (CPPs), micelles, liposomes and even pH-sensitive antibodies (24)(25)(26)(27).…”

Section: Biological Characterisation and Application Of Human Mth1mentioning

confidence: 99%

Biological characterisation and application of human MTH1 and monoclonal antibody preparation

Chen

Li²,

et al. 2018

Oncol Rep

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Human MutT homolog 1 (MTH1) hydrolyses oxidised nucleotide triphosphates, thereby preventing them from being incorporated into DNA; MTH1 has been found to be elevated in many types of cancers, including lung, stomach cancer, melanoma and breast cancer. Thus, tumour-targeted hMTH1 may be valuable for developing novel anticancer therapies. In the present study, we prepared human MTH1 protein and its monoclonal antibody (mAb). The hMTH1 gene was cloned into the prokaryotic expression vector pET28a and optimally expressed in the E. coli Transetta (DE3) strain. Using an Ni-NTA column and a G-50 gel filtration column, 20.1 mg of active hMTH1 was obtained from 1,000 ml of bacterial culture, and the purity was over 98%, as detected by high-performance liquid chromatography (HPLC). The half maximal inhibitory concentration (IC 50 ) of TH287 (hMTH1 inhibitor) was determined to be 3.53±0.47 nM using the recombinant hMTH1 protein (rhMTH1). The enzyme activity assay showed the Michaelis constant (K m ) and the catalytic constant (k cat ) of the protein were 106.13±48.83 µM and 3.64±0.58 sec -1 , respectively. The anti-hMTH1 mAb was obtained via the hybridoma technique and validated by western blot analysis. In addition, an immunofluorescence assay (IFA) and ELISA determined that the mAb could efficiently bind to natural hMTH1 expressed on the human breast cancer cell line MCF-7. Taken together, the results showed the rhMTH1 is an active protein and has practical applications for inhibitor selection, and our prepared hMTH1 mAb will provide a valuable tool for the further characterisation of hMTH1 and antitumour medicinal development in future.

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“…In a third study, Harashima www.advancedsciencenews.com www.advtherap.com . [82] Cationic R8 moiety was utilized to promote the interaction and internalization of nanoparticles. [83] In an earlier study, the authors demonstrated that lipid nanoparticles modified with low and high R8 density were internalized by cells through clathrin-mediated endocytosis and macropinocytosis, respectively.…”

Section: Peptide Lipidsmentioning

confidence: 99%

Intracellular Antibody Delivery Mediated by Lipids, Polymers, and Inorganic Nanomaterials for Therapeutic Applications

et al. 2020

Advanced Therapeutics

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Therapeutic antibodies, due to their high affinity and specificity toward their biological targets, may demonstrate reduced harmful side effects compared with traditional drug moieties. While most of the as-yet clinically approved antibody therapeutics have targeted extracellular or membrane-bound domains, the ability to target intracellular antigens with antibodies opens up tremendous opportunities for imaging, diagnosis, and therapeutic applications. Generally, delivery concerns have limited the ability to target intracellular antigens, as many antibodies cannot easily cross the cell membrane due to their size and surface chemistry. Delivery platforms have been explored to address this issue, including physical methods, fusion protein/peptide techniques, and synthetic carrier-based systems. This review summarizes the progress of carrier-based intracellular antibody delivery systems employing synthetic lipids, polymers, and inorganic nanomaterials. Antibodies targeting various epitopes have been loaded through adsorption, conjugation, or physical encapsulation strategies. Successful intracellular deliveries have been demonstrated largely through fluorescence imaging using dye-labeled antibody cargos. Specific synthetic delivery platforms have great potential for ex vivo and in vivo therapeutic applications. Challenges and opportunities are further discussed for material scientists to explore in this research area.

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Efficient and High-Speed Transduction of an Antibody into Living Cells Using a Multifunctional Nanocarrier System to Control Intracellular Trafficking

Cited by 20 publications

References 41 publications

DOC‐LS, a new liposome for dermal delivery, and its endocytosis by HaCaT and CCC‐ESF‐1 cells

DOC‐LS, a new liposome for dermal delivery, and its endocytosis by HaCaT and CCC‐ESF‐1 cells

Biological characterisation and application of human MTH1 and monoclonal antibody preparation

Intracellular Antibody Delivery Mediated by Lipids, Polymers, and Inorganic Nanomaterials for Therapeutic Applications

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