Tuned Density of Anti-Tissue Factor Antibody Fragment onto siRNA-Loaded Polyion Complex Micelles for Optimizing Targetability into Pancreatic Cancer Cells

Min, Hyun Su; Kim, Hyun Jin; Ahn, Jooyeon; Naito, Mitsuru; Hayashi, Kotaro; Toh, Kazuko; Kim, Beob Soo; Matsumura, Yasuhiro; Kwon, Ick Chan; Miyata, Kanjiro; Kataoka, Kazunori

doi:10.1021/acs.biomac.8b00507

Cited by 40 publications

(29 citation statements)

References 45 publications

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“…Similarly to macrophase separated droplets, PEC micelles can protect proteins from degrading agents to maintain protein activity [142] and secondary structure, and deliver proteins intracellularly via endocytosis [27,29,30,31,123]. The most widely studied application of microphase separated protein PECs involves the use of PEC micelles as nanocarriers for intracellular delivery of protein therapeutics.…”

Section: Recent Development Of Applications and Characterization Tmentioning

confidence: 99%

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Macro- and Microphase Separated Protein-Polyelectrolyte Complexes: Design Parameters and Current Progress

2019

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Protein-containing polyelectrolyte complexes (PECs) are a diverse class of materials, composed of two or more oppositely charged polyelectrolytes that condense and phase separate near overall charge neutrality. Such phase-separation can take on a variety of morphologies from macrophase separated liquid condensates, to solid precipitates, to monodispersed spherical micelles. In this review, we present an overview of recent advances in protein-containing PECs, with an overall goal of defining relevant design parameters for macro- and microphase separated PECs. For both classes of PECs, the influence of protein characteristics, such as surface charge and patchiness, co-polyelectrolyte characteristics, such as charge density and structure, and overall solution characteristics, such as salt concentration and pH, are considered. After overall design features are established, potential applications in food processing, biosensing, drug delivery, and protein purification are discussed and recent characterization techniques for protein-containing PECs are highlighted.

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Section: Recent Development Of Applications and Characterization Tmentioning

confidence: 99%

“…This original microphase separated protein PEC incorporated lysozyme as a model protein. Since then, such systems have shown potential as vehicles for intracellular delivery of proteins and polypeptide therapeutics and as nanostorage devices for the long-term protection and storage of proteins [26,27,28,29,30,31,32,33].…”

Section: Introductionmentioning

confidence: 99%

Macro- and Microphase Separated Protein-Polyelectrolyte Complexes: Design Parameters and Current Progress

2019

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“…The key characteristics required for the development of a BBB‐crossing nanocarrier for ASO delivery are the following: 1) longevity in the blood circulation after systemic injection, 2) feasible density tuning of the glucose ligands exposed on the nanocarrier surface to optimize GLUT1‐mediated transport across the BCEC layer, and 3) smooth cargo ASO release in the appropriate site of action in the brain parenchyma. Thus, we chose a polyion complex micelle (PIC/M) self‐assembled from poly(ethylene glycol)‐ b ‐poly( l ‐lysine) modified with 3‐mercaptopropyl amidine and 2‐thiolaneimine (PEG‐PLL(MPA/IM)) block copolymer and ASO through electrostatic interaction as the platform structure for the BBB‐crossing nanocarrier . The ASO in PIC/M is captured in the core, surrounded by the shell of densely associated PEG strands to ensure longevity in blood circulation.…”

Section: Introductionmentioning

confidence: 99%

“…The ASO in PIC/M is captured in the core, surrounded by the shell of densely associated PEG strands to ensure longevity in blood circulation. Furthermore, disulfide crosslinking is introduced in the PIC/M core by partially derivatizing the side chain of the poly( l ‐lysine) segment in the PEG‐PLL with sulfhydryl groups (Figure ) . In this way, while the PIC/M becomes more robust in the nonreductive blood compartment due to the formation of disulfide crosslinking in the core, it undergoes destabilization in the reductive condition of the brain through the cleavage of disulfide bonds to release the cargo ASO.…”

Section: Introductionmentioning

confidence: 99%

Systemic Brain Delivery of Antisense Oligonucleotides across the Blood–Brain Barrier with a Glucose‐Coated Polymeric Nanocarrier

et al. 2020

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Current antisense oligonucleotide (ASO) therapies for the treatment of central nervous system (CNS) disorders are performed through invasive administration, thereby placing a major burden on patients. To alleviate this burden, we herein report systemic ASO delivery to the brain by crossing the blood–brain barrier using glycemic control as an external trigger. Glucose‐coated polymeric nanocarriers, which can be bound by glucose transporter‐1 expressed on the brain capillary endothelial cells, are designed for stable encapsulation of ASOs, with a particle size of about 45 nm and an adequate glucose‐ligand density. The optimized nanocarrier efficiently accumulates in the brain tissue 1 h after intravenous administration and exhibits significant knockdown of a target long non‐coding RNA in various brain regions, including the cerebral cortex and hippocampus. These results demonstrate that the glucose‐modified polymeric nanocarriers enable noninvasive ASO administration to the brain for the treatment of CNS disorders.

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“…For another, with the development of antibody engineering technology, multiple of antibody fragments that meet the performance requirements can be convenient constructed [21][22][23]. Due to the excellent physicochemical properties of antibody fragments and the diversity of targeted cancer treatment and diagnostic methods, more and more researchers and research institutions are actively exploring the application of antibody fragments in tumour therapy and imaging.…”

Section: Introductionmentioning

confidence: 99%

A promising cancer diagnosis and treatment strategy: targeted cancer therapy and imaging based on antibody fragment

Zhao

Ning

Zhang

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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With the arrival of the precision medicine and personalized treatment era, targeted therapy that improves efficacy and reduces side effects has become the mainstream approach of cancer treatment. Antibody fragments that further enhance penetration and retain the most critical antigen-specific binding functions are considered the focus of research targeting cancer imaging and therapy. Thanks to the superior penetration and rapid blood clearance of antibody fragments, antibody fragment-based imaging agents enable efficient and sensitive imaging of tumour sites. In tumour-targeted therapy, antibody fragments can directly inhibit tumour proliferation and growth, serve as an ideal carrier for delivery of anti-tumour drugs, or manipulate the immune system to eliminate tumour cells. In this review, the excellent physicochemical properties and the basic structure of antibody fragments are expressly depicted depicted, the progress of antibody fragments in cancer therapy and imaging are thoroughly summarized, and the future development of antibody fragments is predicted.

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Tuned Density of Anti-Tissue Factor Antibody Fragment onto siRNA-Loaded Polyion Complex Micelles for Optimizing Targetability into Pancreatic Cancer Cells

Cited by 40 publications

References 45 publications

Macro- and Microphase Separated Protein-Polyelectrolyte Complexes: Design Parameters and Current Progress

Macro- and Microphase Separated Protein-Polyelectrolyte Complexes: Design Parameters and Current Progress

Systemic Brain Delivery of Antisense Oligonucleotides across the Blood–Brain Barrier with a Glucose‐Coated Polymeric Nanocarrier

A promising cancer diagnosis and treatment strategy: targeted cancer therapy and imaging based on antibody fragment

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