iBodies: Modular Synthetic Antibody Mimetics Based on Hydrophilic Polymers Decorated with Functional Moieties

Abstract

Antibodies are indispensable tools for biomedicine and anticancer therapy. Nevertheless,their use is compromised by high production costs,l imited stability,a nd difficulty of chemical modification. The design and preparation of synthetic polymer conjugates capable of replacing antibodies in biomedical applications such as ELISA, flow cytometry,i mmunocytochemistry,a nd immunoprecipitation is reported. The conjugates,named "iBodies", consist of an HPMA copolymer decorated with low-molecular-weight compounds that function as targeting ligands,a ffinity anchors,a nd imaging probes.W e prepared specific conjugates targeting several proteins with knownl igands and used these iBodies for enzyme inhibition, protein isolation, immobilization, quantification, and live-cell imaging.O ur data indicate that this highly modular and versatile polymer system can be used to produce inexpensive and stable antibody substitutes directed towardv irtually any protein of interest with aknown ligand.

A tumor-targeted polymer theranostics platform for positron emission tomography and fluorescence imaging

“…The polymerization conditions were adapted from our previous works. 19, 21 The content of the hydrazide or TT groups in the polymer precursors was sufficient for further attachment of fluorescent dyes, drug or chelator, respectively.…”

“…The random copolymers poly(HPMA- co -MA-APr-TT) with narrow distribution of molecular weight (LD-P(TT)-30 and LD-P(TT)-45) were prepared by the RAFT polymerization of HPMA with MA-APr-TT, followed by dithiobenzoate end group removal. Polymerizations were adapted from previous works 19, 21 using 2-cyanopropan-2-yl benzodithioate as chain transfer agent (CTA) and AIBN as initiator at 70 °C for 16 h in the mixture of 85 % of tert -butyl alcohol and 15 % of DMSO. The molar ratio of monomers: CTA: initiator were 400: 2: 1 for LD-P(hyd)-30, 600: 2: 1 for LD-P(hyd)-45, 550: 2: 1 for LD-P(TT)-30 and 700: 2: 1 for LD-P(TT)-45.…”

Polymer-tethered quenched fluorescent probes for enhanced imaging of tumor associated proteases

“…Furthermore, the macromolecular scaffold can be used to attach additional affinity-based targeting elements and to control the overall location and stoichiometry of quencher-fluorophore pairs. A recently developed class of macromolecular antibody mimetics, called iBodies, employs a plat-form based on N-(2-hydroxypropyl)methacrylamide copolymer (pHPMA) 17. The concept of iBodies is based on facile derivatization in the polymer side chain with high-affinity ligands or inhibitors, fluorescent dyes and/or appropriate affinity tags, such as biotin, all on the same pHPMA carrier.…”

Polymer-Tethered Quenched Fluorescent Probes for Enhanced Imaging of Tumor-Associated Proteases

“…A recently developed class of macromolecular antibody mimetics, called iBodies, employs a platform based on N-(2-hydroxypropyl)methacrylamide copolymer (pHPMA). 17 The concept of iBodies is based on facile derivatization in the polymer side chains with high-affinity ligands or inhibitors, fluorescent dyes, and/or appropriate affinity tags, such as biotin, all on the same pHPMA carrier. Modular iBodies are similar to antibodies with high affinity but with increased overall functionality and design flexibility, similar to synthetic small molecules.…”