Molecularly Imprinted Polymer Hydrogel Nanoparticles: Synthetic Antibodies for Cancer Diagnosis and Therapy

Bui, Bernadette Tse Sum; Haupt, Karsten

doi:10.1002/cbic.202100598

Cited by 18 publications

(9 citation statements)

References 84 publications

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“…[15] Due to their small size and the possibility of surface modification with biological ligands or molecular imprinting, nanocarriers can easily cross biological barriers, which have limited pore sizes (fenestrations) under 1 micron in most cases, then target and enter the tissues or cells of interest. [16,17] Due to these aspects and the possibility of controlling drug distribution and release through particle engineering, nanocarriers can thus reduce systemic side effects and enhance the therapeutic efficacy of drugs. [15] Nanosystems can also offer unique advantages for biomedical imaging with their ability of sensing, image enhancement, and incorporating concomitantly therapeutic agents for theranostics, that is, simultaneous therapeutic and diagnostic applications.…”

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confidence: 99%

Colloidal Polyelectrolyte Complexes from Hyaluronic Acid: Preparation and Biomedical Applications

Cerf

2022

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nanocomplexes, [8,9] nanocomposites, [10,11] nanoassemblies [12] and coacervates. [13,14] Such colloidal systems, especially when prepared from biopolymers, have been extensively investigated due to their promising properties for numerous applications in biomedical fields. [1] Their merits come from the combination of three aspects: nanomedicine, biomaterials, and green chemistry. With the emergence of nanomedicine, the use of nanocarriers can offer tremendous advantages in drug encapsulation and delivery, namely enhancing the chemical stability of drugs and improving drug solubility and bioavailability. [15] Due to their small size and the possibility of surface modification with biological ligands or molecular imprinting, nanocarriers can easily cross biological barriers, which have limited pore sizes (fenestrations) under 1 micron in most cases, then target and enter the tissues or cells of interest. [16,17] Due to these aspects and the possibility of controlling drug distribution and release through particle engineering, nanocarriers can thus reduce systemic side effects and enhance the therapeutic efficacy of drugs. [15] Nanosystems can also offer unique advantages for biomedical imaging with their ability of sensing, image enhancement, and incorporating concomitantly therapeutic agents for theranostics, that is, simultaneous therapeutic and diagnostic applications. [18][19][20] When constructed from biomaterials, especially naturally occurring polysaccharides or proteins, PECs can become significantly biocompatible and biodegradable with much less immunogenicity and toxicity. [21] Besides such biorelevant aspects, the elaboration of biopolymerbased PECs is also in accordance with green chemistry principles since their preparation process usually requires only gentle mixing of polyelectrolyte solutions at room temperature, which is a simple and rapid procedure without the need for chemical agents, surfactants, organic solvents or high mechanical or thermal energy. [15] Beyond the above-mentioned basic advantages, the potential of colloidal PEC systems is increased by the inherent biological and chemical properties of individual constituent polymers. Hyaluronic acid (HA), also called hyaluronan to generally mention both its acid and salt forms, has been one of the most common polyanions among several biopolymers reported so far for the elaboration of colloidal PECs. The significant attention dedicated to HA in biomedical fields is associated with its unique advantages, stemming from not only its outstanding biocompatibility but also interesting biological activities. [22] Hyaluronic acid (HA) is a naturally occurring polysaccharide which has been extensively exploited in biomedical fields owing to its outstanding biocompatibility. Self-assembly of HA and polycations through electrostatic interactions can generate colloidal polyelectrolyte complexes (PECs), which can offer a wide range of applications while being relatively simple to prepare with rapid and "green" processes. The advantages of colloidal HA-base...

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confidence: 99%

Colloidal Polyelectrolyte Complexes from Hyaluronic Acid: Preparation and Biomedical Applications

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2022

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“…It is very likely that this is a sine qua non condition to bring MIPs to future in vivo applications. Concerning the fate of the MIP‐NGs after injection into the bloodstream, it has been reported that they will be eventually cleared by the liver [14b,c] …”

Section: Discussionmentioning

confidence: 99%

Synthetic Peptide Antibodies as TNF‐α Inhibitors: Molecularly Imprinted Polymer Nanogels Neutralize the Inflammatory Activity of TNF‐α in THP‐1 Derived Macrophages

et al. 2023

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Tumor Necrosis Factor‐α (TNF‐α) is a cytokine that is normally produced by immune cells when fighting an infection. But, when too much TNF‐α is produced as in autoimmune diseases, this leads to unwanted and persistent inflammation. Anti‐TNF‐α monoclonal antibodies have revolutionized the therapy of these disorders by blocking TNF‐α and preventing its binding to TNF‐α receptors, thus suppressing the inflammation. Herein, we propose an alternative in the form of molecularly imprinted polymer nanogels (MIP‐NGs). MIP‐NGs are synthetic antibodies obtained by nanomoulding the 3‐dimensional shape and chemical functionalities of a desired target in a synthetic polymer. Using an in‐house developed in silico rational approach, epitope peptides of TNF‐α were generated and ‘synthetic peptide antibodies’ were prepared. The resultant MIP‐NGs bind the template peptide and recombinant TNF‐α with high affinity and selectivity, and can block the binding of TNF‐α to its receptor. Consequently they were applied to neutralize pro‐inflammatory TNF‐α in the supernatant of human THP‐1 macrophages, leading to a downregulation of the secretion of pro‐inflammatory cytokines. Our results suggest that MIP‐NGs, which are thermally and biochemically more stable and easier to manufacture than antibodies, and cost‐effective, are very promising as next generation TNF‐α inhibitors for the treatment of inflammatory diseases.

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“…Many chemical methods exist already for immobilizing the epitope in an oriented configuration on a solid‐phase support. [ 24 ] When the subsequent polymerization is conducted with hydrophilic monomers in a dilute aqueous solution, this strategy gives rise to biocompatible water soluble MIP nanogels (MIP‐NGs) with homogeneous binding sites, comparable to monoclonal‐type antibodies. [ 4d ] These can advantageously be used in applications such as medical diagnostics (immunoassays, immunosensors, immunohistochemistry, flow cytometry) and therapy.…”

Section: Mips For Proteins: Where Do We Stand?mentioning

confidence: 99%

“…[62] Molecules other than amino acids are often added to the peptide template to act as linkers for the immobilization on a solid support. Some of the reported linkers used for template immobilization are fructose, [45] His-tag, [63] Flag-tag, [64] and azide or alkyne groups [24,40,58] for click chemistry reactions. In addition, the immobilization of the templates can take place through the existing carboxylic or amino groups of the peptide by a carbodiimide crosslinking reaction (EDC/NHS) [21] or residues like cysteine can be added for immobilization on iodoacetate-functionalized surfaces.…”

Section: Structural Design Of Epitopesmentioning

confidence: 99%

Molecularly Imprinted Polymers as Synthetic Antibodies for Protein Recognition: The Next Generation

Bui

Mier

Haupt

2023

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Molecularly imprinted polymers (MIPs) are chemical antibody mimics obtained by nanomoulding the 3D shape and chemical functionalities of a desired target in a synthetic polymer. Consequently, they possess exquisite molecular recognition cavities for binding the target molecule, often with specificity and affinity similar to those of antigen‐antibody interactions. Research on MIPs targeting proteins began in the mid‐90s, and this review will evaluate the progress made till now, starting from their synthesis in a monolith bulk format through surface imprinting to biocompatible soluble nanogels prepared by solid‐phase synthesis. MIPs in the latter format will be discussed more in detail because of their tremendous potential of replacing antibodies in the biomedical domain like in diagnostics and therapeutics, where the workforce of antibodies is concentrated. Emphasis is also put on the development of epitope imprinting, which consists of imprinting a short surface‐exposed fragment of a protein, resulting in MIPs capable of selectively recognizing the whole macromolecule, amidst others in complex biological media, on cells or tissues. Thus selecting the ‘best’ peptide antigen is crucial and in this context a rational approach, inspired from that used to predict peptide immunogens for peptide antibodies, is described for its unambiguous identification.

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Molecularly Imprinted Polymer Hydrogel Nanoparticles: Synthetic Antibodies for Cancer Diagnosis and Therapy

Cited by 18 publications

References 84 publications

Colloidal Polyelectrolyte Complexes from Hyaluronic Acid: Preparation and Biomedical Applications

Colloidal Polyelectrolyte Complexes from Hyaluronic Acid: Preparation and Biomedical Applications

Synthetic Peptide Antibodies as TNF‐α Inhibitors: Molecularly Imprinted Polymer Nanogels Neutralize the Inflammatory Activity of TNF‐α in THP‐1 Derived Macrophages

Molecularly Imprinted Polymers as Synthetic Antibodies for Protein Recognition: The Next Generation

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