Antibody Delivery for Intracellular Targets: Emergent Therapeutic Potential

Singh, Khushboo; Ejaz, Wardah; Dutta, Kingshuk; Thayumanavan, S.

doi:10.1021/acs.bioconjchem.9b00025

Cited by 69 publications

(69 citation statements)

References 162 publications

(273 reference statements)

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“…Monoclonal Ab‐based therapies had shown a great potential owing to their target specificity and low immunogenicity; however, main drawbacks such as low circulating times and intracellular delivery have urged the development of numerous Ab intracellular delivery strategies (such as virus‐like carriers, cell‐penetrating peptides, organic or inorganic NPs, lipid‐based particles, etc.) 15,16b . Biomimetic‐derived nMBs may provide a suitable alternative for efficient Ab intracellular delivery 36.…”

Section: Resultsmentioning

confidence: 99%

“…Although Abs can be engineered to target a wide range of antigens, Ab‐based therapeutics are typically restricted to permeabilized cells or targeting of extracellular antigens; thus, Ab‐targeting of intracellular biomarkers remains a challenge 15. The development of novel approaches for cytosolic delivery of Abs is crucial to target intracellular proteins that, for instance, act as immune checkpoints or to target cancer‐causing molecules.…”

Section: Introductionmentioning

confidence: 99%

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Plasmonic Cell‐Derived Nanocomposites for Light‐Controlled Cargo Release inside Living Cells

et al. 2020

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Translating the potential of thermoplasmonics to cell‐derived nanomaterials offers exciting opportunities to fabricate beyond state‐of‐art artificial biomimetic nanocomposites that upon illumination perform active tasks such as delivery of cargo in complex, dynamic media such as the cytosol of cells. Cell‐derived nanoparticles have shown stunning potential to implement cell‐specific functions, such as long blood circulation or targeting capabilities, into advanced drug delivery nanosystems. The biomimicry nanotechnology has now advanced to offer new and exciting opportunities to improve the commonly poor in vivo performance of most current nanomedicines, including evading the immune system and targeting specific tissues such as tumors, the latest remaining among the most wanted breakthroughs in nanomedicine. However, the use of cell‐derived nanocomposites as stimulus‐controlled drug delivery agents remains virtually unexplored. This study reports the fabrication of a plasmonic cell‐derived nanocomposite by integrating near‐infrared active gold nanorods in its structure. As a proof of concept, the plasmonic nanomembranes are loaded with cell non‐permeant antibodies, which upon near‐infrared stimulation can be released from the plasmonic nanomembranes into the cytosol of living cells, without impairing cell viability or the antibodies' function. These results set the stage for the development of photoactive cell‐derived nanocarriers, which in addition to cell‐specific functions promise straightforward access to spatiotemporal‐controlled intracellular delivery of antibodies.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Plasmonic Cell‐Derived Nanocomposites for Light‐Controlled Cargo Release inside Living Cells

et al. 2020

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“…Intrabodies are internally expressed antibodies. Gene transport mechanisms are used to deliver the DNA encoding the therapeutic antibody or antibody fragment inside the cell where it can be transcribed ( Figure 8 A) [ 31 , 32 , 141 ]. Another method of internalizing Abs is to pair them with a membrane-penetrating peptide (MPP).…”

Section: T3ss Components Targeted By Antibodiesmentioning

confidence: 99%

Antibodies Inhibiting the Type III Secretion System of Gram-Negative Pathogenic Bacteria

Hotinger

May

2020

Antibodies

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Pathogenic bacteria are a global health threat, with over 2 million infections caused by Gram-negative bacteria every year in the United States. This problem is exacerbated by the increase in resistance to common antibiotics that are routinely used to treat these infections, creating an urgent need for innovative ways to treat and prevent virulence caused by these pathogens. Many Gram-negative pathogenic bacteria use a type III secretion system (T3SS) to inject toxins and other effector proteins directly into host cells. The T3SS has become a popular anti-virulence target because it is required for pathogenesis and knockouts have attenuated virulence. It is also not required for survival, which should result in less selective pressure for resistance formation against T3SS inhibitors. In this review, we will highlight selected examples of direct antibody immunizations and the use of antibodies in immunotherapy treatments that target the bacterial T3SS. These examples include antibodies targeting the T3SS of Pseudomonas aeruginosa, Yersinia pestis, Escherichia coli, Salmonella enterica, Shigella spp., and Chlamydia trachomatis.

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“…Along these lines, liposomes were recently proposed to constitute a promising carrier for intracellular trafficking of therapeutic antibodies against molecules located within the cell [ 107 ]. On the contrary, cell targeting by liposomes and other synthetic nanoparticles can be conferred by functionalizing their surface with specific antibodies [ 108 ].…”

Section: Perspectives In Manipulating Evs For Therapeutic Applicatmentioning

confidence: 99%

Perspectives in Manipulating EVs for Therapeutic Applications: Focus on Cancer Treatment

Nazimek

Bryniarski

2020

IJMS

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Extracellular vesicles (EVs) receive special attention from oncologists due to their assumed usefulness as prognostic markers, vaccines to induce anti-cancer immune response, and physiological delivery tools. The latter application, which supports the reduction of side effects of treatment, is still fraught with many challenges, including established methods for loading EVs with selected cargo and directing them towards target cells. EVs could be loaded with selected cargo either in vitro using several physicochemical techniques, or in vivo by modification of parental cell, which may have an advantage over in vitro procedures, since some of them significantly influence EVs’ properties. Otherwise, our research findings suggest that EVs could be passively supplemented with micro RNAs (miRNAs) or miRNA antagonists to induce expected biological effect. Furthermore, our observations imply that antigen-specific antibody light chains could coat the surface of EVs to increase the specificity of cell targeting. Finally, the route of EVs’ administration also determines their bioavailability and eventually induced therapeutic effect. Besides, EV membrane lipids may possibly possess immune adjuvant activity. The review summarizes the current knowledge on the possibilities to manipulate EVs to use them as a delivery tool, with the special emphasis on anti-cancer therapy.

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Antibody Delivery for Intracellular Targets: Emergent Therapeutic Potential

Cited by 69 publications

References 162 publications

Plasmonic Cell‐Derived Nanocomposites for Light‐Controlled Cargo Release inside Living Cells

Plasmonic Cell‐Derived Nanocomposites for Light‐Controlled Cargo Release inside Living Cells

Antibodies Inhibiting the Type III Secretion System of Gram-Negative Pathogenic Bacteria

Perspectives in Manipulating EVs for Therapeutic Applications: Focus on Cancer Treatment

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