Functional Virus-Based Polymer–Protein Nanoparticles by Atom Transfer Radical Polymerization

Pokorski, Jonathan K.; Breitenkamp, Kurt; Liepold, Lars; Qazi, Shefah; Finn, M. G.

doi:10.1021/ja203286n

Cited by 173 publications

(176 citation statements)

References 44 publications

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“…It was found that the overall structure was maintained even until 100 °C. Using the same approach for surface functionalization only with a radical initiator attached to the azide instead of a linear polymer, various polymers were grown from the surface via ATRP as described above [74]. The interesting thing is that there are several aspects, which can be combined in a viral-polymer system.…”

Section: Virus-polymer Conjugatesmentioning

confidence: 99%

Polymer Directed Protein Assemblies

Rijn

2013

Polymers

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Protein aggregation and protein self-assembly is an important occurrence in natural systems, and is in some form or other dictated by biopolymers. Very obvious influences of biopolymers on protein assemblies are, e.g., virus particles. Viruses are a multi-protein assembly of which the morphology is dictated by poly-nucleotides namely RNA or DNA. This "biopolymer" directs the proteins and imposes limitations on the structure like the length or diameter of the particle. Not only do these bionanoparticles use polymer-directed self-assembly, also processes like amyloid formation are in a way a result of directed protein assembly by partial unfolded/misfolded biopolymers namely, polypeptides. The combination of proteins and synthetic polymers, inspired by the natural processes, are therefore regarded as a highly promising area of research. Directed protein assembly is versatile with respect to the possible interactions which brings together the protein and polymer, e.g., electrostatic, v.d. Waals forces or covalent conjugation, and possible combinations are numerous due to the large amounts of different polymers and proteins available. The protein-polymer interacting behavior and overall morphology is envisioned to aid in clarifying protein-protein interactions and are thought to entail some interesting new functions and properties which will ultimately lead to novel bio-hybrid materials.

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Section: Virus-polymer Conjugatesmentioning

confidence: 99%

Polymer Directed Protein Assemblies

Rijn

2013

Polymers

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“…Among these technologies, platforms based on polymeric materials, especially biodegradable nanoparticles, are of particular interest due to the flexibility offered by macromolecular synthesis methods, high drug loading capacities, improved drug solubility, and their ease of multifunctionalization. [23][24][25] In this review, the developments in fluorescence imaging with the three polymer based platforms: cross-linked micelles, polymersomes and polymercore nanoparticles (cf. Figure 2), when coupled with the commonly used fluorophores, will be explored.…”

Section: Introductionmentioning

confidence: 99%

Mini-review: fluorescence imaging in cancer cells using dye-doped nanoparticles

2016

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Fluorescence imaging has gained increased attention over the past two decades as a viable means to detect a variety of cancers. Fluorescence imaging has the potential to provide physicians with high resolution images with enhanced contrast, which will allow them to be able to better diagnose and treat patients with cancer. Early detection and treatment are key to erradicating cancer in a patient, and fluorescence imaging has the ability to identify non-advanced, even pre-cancerous, tumors where imaging based on white light or radiation overlooked them. Several fluorescent dyes have been identified as possible fluorophores for enhanced fluorescence imaging, such as cyanine, squaraine, porphyrin, phthalocyanine, and borondipyrromethane dyes. These dyes have high fluorescence quantum yields, which provides a high target to background ratio; however, these dyes are often plagued by low water solubility. This low solubility can be ameliorated by conjugating or covalently attaching these dyes to polymeric crosslinked micelles, polymersomes, or polymer-core nanoparticles. These particle & dye systems then can become platforms on which secondary components can be attached to enhance the systems functionality. For example, dyes attached to these nanocarriers can target tumors through passive targeting; however, active targeting can be achieved by further modifying these nanocarriers with ligands that have a binding affinity for receptors overexpressed in tumor cells, cell surface receptors located on the tumor cell membrane, or endothelium. Fluorescence activation of the probes is another promising technology for the early detection of cancer. Activation requires that there be a change in fluorescence, whether it be an emission wavelength change or a fluorescence "on/off" signal when in the presence of some external stimuli. Activation increase the target to background ratio and enhances the contrast of the obtained image. This review serves to highlight the recent developments of (1) improved fluorescent dyes for the detection of cancer, with a specific focus on dyes that are being coupled to nanocarriers; (2) dye & nanocarrier systems that target, both actively and passively, tumors, and (3) fluorescence activation of these fluorophore systems for better image quality.

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“…3,24−29 The versatility of RDRP techniques has also been further demonstrated in a rapidly growing area of bioconjugations using a "grafting-from" strategy, which uses a protein as a macroinitiator or macrochain transfer agent to grow polymers directly from the protein. 2,7,14,30,31,32 The grafting-from method provides some advantages compared to the grafting-to method such as purification (e.g., separation of unreacted monomers vs separation of unreacted polymers) and control over the number of polymers per protein.…”

Section: ■ Introductionmentioning

confidence: 99%

Role of Polymer Architecture on the Activity of Polymer–Protein Conjugates for the Treatment of Accelerated Bone Loss Disorders

et al. 2015

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Polymers of similar molecular weights and chemical constitution but varying in their macromolecular architectures were conjugated to osteoprotegerin (OPG) to determine the effect of polymer topology on protein activity in vitro and in vivo. OPG is a protein that inhibits bone resorption by preventing the formation of mature osteoclasts from the osteoclast precursor cell. Accelerated bone loss disorders, such as osteoporosis, rheumatoid arthritis, and metastatic bone disease, occur as a result of increased osteoclastogenesis, leading to the severe weakening of the bone. OPG has shown promise as a treatment in bone disorders; however, it is rapidly cleared from circulation through rapid liver uptake, and frequent, high doses of the protein are necessary to achieve a therapeutic benefit. We aimed to improve the effectiveness of OPG by creating OPG-polymer bioconjugates, employing reversible addition-fragmentation chain transfer polymerization to create well-defined polymers with branching densities varying from linear, loosely branched to densely branched. Polymers with each of these architectures were conjugated to OPG using a "grafting-to" approach, and the bioconjugates were characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The OPG-polymer bioconjugates showed retention of activity in vitro against osteoclasts, and each bioconjugate was shown to be nontoxic. Preliminary in vivo studies further supported the nontoxic characteristics of the bioconjugates, and measurement of the bone mineral density in rats 7 days post-treatment via peripheral quantitative computed tomography suggested a slight increase in bone mineral density after administration of the loosely branched OPG-polymer bioconjugate.

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Functional Virus-Based Polymer–Protein Nanoparticles by Atom Transfer Radical Polymerization

Cited by 173 publications

References 44 publications

Polymer Directed Protein Assemblies

Polymer Directed Protein Assemblies

Mini-review: fluorescence imaging in cancer cells using dye-doped nanoparticles

Role of Polymer Architecture on the Activity of Polymer–Protein Conjugates for the Treatment of Accelerated Bone Loss Disorders

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