Molecularly Imprinted Polymers for Cell Recognition

Since their conception 50 years ago, molecularly imprinted polymers (MIPs) have seen extensive development both in terms of synthetic routes and applications. Cells are perhaps the most challenging target for molecular imprinting. Although early work was based almost entirely around microprinting methods, recent developments have shifted towards epitope imprinting to generate MIP nanoparticles (NPs). Simultaneously, the development of techniques such as solid phase MIP synthesis has solved many historic issues of MIP production. This review briefly describes various approaches used in cell imprinting with a focus on applications of the created materials in imaging, drug delivery, diagnostics, and tissue engineering

In Vivo Recognition of Human Vascular Endothelial Growth Factor by Molecularly Imprinted Polymers

One of the mechanisms responsible for cancer-induced increased blood supply in malignant neoplasms is the overexpression of vascular endothelial growth factor (VEGF). Several antibodies for VEGF targeting have been produced for both imaging and therapy. Molecularly imprinted polymer nanoparticles, nanoMIPs, however, offer significant advantages over antibodies, in particular in relation to improved stability, speed of design, cost and control over functionalization. In the present study, the successful production of nanoMIPs against human VEGF is reported for the first time. NanoMIPs were coupled with quantum dots (QDs) for cancer imaging. The composite nanoparticles exhibited specific homing toward human melanoma cell xenografts, overexpressing hVEGF, in zebrafish embryos. No evidence of this accumulation was observed in control organisms. These results indicate that nanoMIPs are promising materials which can be considered for advancing molecular oncological research, in particular when antibodies are less desirable due to their immunogenicity or long production time

Carboxyl-fentanyl detection using optical fibre grating-based sensors functionalised with molecularly imprinted nanoparticles

Butyrylfentanyl is a new designer drug reported with growing use and related deaths. Routine toxicological analyses of this novel synthetic opioid drug have not been established yet. This work reports a fibre optic sensor that measures carboxyl-fentanyl which is the major metabolite of butyrylfentanyl presented in blood, providing a promising tool for detecting butyrylfentanyl intoxication. A long period fibre grating (LPG) sensor array operating at phase-matching condition is deployed in combination with a state-of-the-art molecular imprinting technique. Nano-sized molecularly imprinted polymers (nanoMIPs) are synthesised via a solid-phase approach and coated on the surface of an LPG array. An LPG array consists of two parts: a detection and a reference LPG. The former is functionalised with nanoMIPs prior to the measurements, whilst the latter is used to take into account the temperature response of the detection LPG. The developed sensor exhibits a gradual response over increasing concentrations of carboxyl-fentanyl from 0 to 1000 ng/mL with a minimal detected concentration of 50 ng/mL, that corresponds to a wavelength shift of 1.20 ± 0.2 nm. The Langmuir adsorption isotherm is applied to fit the analytical data which reveal a binding constant of 2.03 μM-1. The developed sensor shows high selectivity in detecting carboxyl-fentanyl among other drugs and potential interferents including morphine, cocaine, glucose and albumin. It shows a certain degree of cross-response to fentanyl which shares the same binding sites as carboxyl-fentanyl and therefore can be potentially used to detect fentanyl

Molecularly Imprinted Nanoparticles for Diagnostic Applications

Molecularly imprinted polymers (MIP) are gaining increasing interest thanks to their low cost of manufacturing, robustness and stability compared to their bio-analogues such as antibodies. The molecular imprinting process can be defined as the generation of molecular recognition sites in a synthetic polymer. The template-derived sites thus created within the polymeric matrix allow MIPs (often referred as plastic antibodies, due to their synthetic nature) to selectively recognise and bind the target molecule. In light of these properties, MIPs have been successfully applied in sensors, assays and separation applications. Due to their small size, MIP nanoparticles (NPs or nanoMIPs) can be used in biomedicine, since the nanoscale format is potentially suitable for cellular or in vivo applications. The aim of this work is to demonstrate the suitability of the nanoMIPs as tools for imaging in cells. For this purpose, the choice of appropriate fluorescent moieties to be included in the nanoMIPs is crucial and depends on the intended application. Several fluorescent monomers were characterised and chosen as imaging functionalities to be employed in the synthesis of MIP NPs (Chapter 2). The innovative solid-phase approach used in this work enables the synthesis of nanoMIPs both in organics (for small templates) and in water (for peptides and proteins), with the possibility to tailor the particle’s surface chemistry according to the intended use. (Chapter 3 and 4). Only few examples of MIP NPs for cellular imaging have been reported so far. Such nanosystems should be biocompatible and physiochemically stable under physiological conditions, as demonstrated in Chapter 5 and 6. Thanks to their good biocompatibility and recognition properties, MIP NPs were successfully applied as membrane-targeted diagnostic tools (Chapter 7) in both cancer and senescent cells, thus paving the way for their in vivo use as diagnostic and imaging tools

Generation of High-Affinity Molecularly Imprinted Nanoparticles for Protein Recognition via a Solid-Phase Synthesis Protocol

Molecularly imprinted polymers are leading technology in the development of protein biomimetics. This chapter describes the protocol for the synthesis of protein imprinted nanoparticles. These materials exhibit exceptional affinity (into the nM/pM range) and selectivity for their target template. The nanoparticles can be developed for a wide range of targets, while exhibiting excellent robustness, solubility, and flexibility in use. They are finding use in the creation of drug delivery vectors and sensing and recognition assays

Polymeric nanoparticles for optical sensing

Nanotechnology is a powerful tool for use in diagnostic applications. For these purposes a variety of functional nanoparticles containing fluorescent labels, gold and quantum dots at their cores have been produced, with the aim of enhanced sensitivity and multiplexing capabilities. This work will review progress in the application of polymeric nanoparticles in optical diagnostics, both for in vitro and in vivo detection, together with a discussion of their biodistribution and biocompatibility

Correction: An impedimetric sensor based on molecularly imprinted nanoparticles for the determination of trypsin in artificial matrices – towards point-of-care diagnostics

: Correction for 'An impedimetric sensor based on molecularly imprinted nanoparticles for the determination of trypsin in artificial matrices - towards point-of-care diagnostics' by Sabrina Di Masi et al., Anal. Methods, 2024, 16, 742-750, https://doi.org/10.1039/D3AY01762A