92
biocompatible and stable. The use of the solid-phase approach in the synthesis
allowed to protect the binding sites of MIN during grafting, without affecting their
recognition properties (Moczko et al. 2013). Xu et al. (2017a) also developed synthetic antibodies based on a fluorescent core-shell MIP to bind trypsin. Here, the
core was made of MIN prepared by multistep solid-phase synthesis. The shell was
grafted in situ on the core-MIP, while the binding cavities were still bound to trypsin. The composition of the shell allowed conjugation with a fluorophore to obtain
a fluorescent core-shell with possibility of mimicking antibodies in an immunoassay. Canfarotta et al. (2016b) proposed the surface modification of MIN by synthesizing the solid-phase approach using poly(ethylene glycol) polymers with different
Mws: 1100 and 4000 Da. These authors reported the effects of surface modification
on the cytotoxicity, internalization and stability of MIN. These results represented
an advance in the knowledge of the biocompatibility of MIN, paving the way for in
vivo applications (Canfarotta et al. 2016b).
More recently, Sayour et al. (2019) developed a core-shell material based on the
modification of yttrium oxide NPs with a functional polymer layer. The polymer
layer decreased the surface energy of the NPs, increasing its polarity and, as a result,
improved its colloidal stability. In addition, the polymer improved the biocompatibility of NPs, which were toxic in themselves, which allowed their use for therapeutic applications (Sayour et al. 2019).
5.3.3 MIP Membranes
The preparation of molecularly imprinted membranes (MIM) can be done through
in situ polymerization or by ‘post implanting’ methods. Keeping this in view, the
membrane can be composed of a MIP or can contain a MIP. MIMs have outstanding
advantages, such as large specific surfaces and fine porous structures, which favor
the template accessibility to imprinted sites (Scorrano et al. 2015).
The control of the density and affinity of imprinted sites and the adequate morphology of the membrane pores are critical factors that contribute to the good performance of MIMs. In membranes having meso- or micropores binding sites can
even change the network of pores, thereby modifying membrane permeability,
which is known as ‘gate effect’. In order to improve MIM selectivity, morphology
and even permeability, it is necessary to control the polymer density, flexibility,
density the amount of specific binding sites and its swelling/shrinking capability in
the presence of the template. The degree of polymerization and the polymer structure can be controlled using controlled living radical polymerization methods.
Three different strategies have been proposed for the development and the preparation of MIM from previously synthesized MIP particles, the preparation of MIPs
on or in support membranes with adequate morphology and the simultaneous formation of imprinted sites and the membrane itself. In the latter approach, imprinted
sites and the membrane structure are prepared by in situ radical polymerization
using solutions of acrylate/vinyl monomers and the template (Sergeyeva et al. 2003;
Lin et al. 2008). An alternative to this crosslinking in situ may be polymer solution
A. Gómez-Caballero et al.
biocompatible and stable. The use of the solid-phase approach in the synthesis
allowed to protect the binding sites of MIN during grafting, without affecting their
recognition properties (Moczko et al. 2013). Xu et al. (2017a) also developed synthetic antibodies based on a fluorescent core-shell MIP to bind trypsin. Here, the
core was made of MIN prepared by multistep solid-phase synthesis. The shell was
grafted in situ on the core-MIP, while the binding cavities were still bound to trypsin. The composition of the shell allowed conjugation with a fluorophore to obtain
a fluorescent core-shell with possibility of mimicking antibodies in an immunoassay. Canfarotta et al. (2016b) proposed the surface modification of MIN by synthesizing the solid-phase approach using poly(ethylene glycol) polymers with different
Mws: 1100 and 4000 Da. These authors reported the effects of surface modification
on the cytotoxicity, internalization and stability of MIN. These results represented
an advance in the knowledge of the biocompatibility of MIN, paving the way for in
vivo applications (Canfarotta et al. 2016b).
More recently, Sayour et al. (2019) developed a core-shell material based on the
modification of yttrium oxide NPs with a functional polymer layer. The polymer
layer decreased the surface energy of the NPs, increasing its polarity and, as a result,
improved its colloidal stability. In addition, the polymer improved the biocompatibility of NPs, which were toxic in themselves, which allowed their use for therapeutic applications (Sayour et al. 2019).
5.3.3 MIP Membranes
The preparation of molecularly imprinted membranes (MIM) can be done through
in situ polymerization or by ‘post implanting’ methods. Keeping this in view, the
membrane can be composed of a MIP or can contain a MIP. MIMs have outstanding
advantages, such as large specific surfaces and fine porous structures, which favor
the template accessibility to imprinted sites (Scorrano et al. 2015).
The control of the density and affinity of imprinted sites and the adequate morphology of the membrane pores are critical factors that contribute to the good performance of MIMs. In membranes having meso- or micropores binding sites can
even change the network of pores, thereby modifying membrane permeability,
which is known as ‘gate effect’. In order to improve MIM selectivity, morphology
and even permeability, it is necessary to control the polymer density, flexibility,
density the amount of specific binding sites and its swelling/shrinking capability in
the presence of the template. The degree of polymerization and the polymer structure can be controlled using controlled living radical polymerization methods.
Three different strategies have been proposed for the development and the preparation of MIM from previously synthesized MIP particles, the preparation of MIPs
on or in support membranes with adequate morphology and the simultaneous formation of imprinted sites and the membrane itself. In the latter approach, imprinted
sites and the membrane structure are prepared by in situ radical polymerization
using solutions of acrylate/vinyl monomers and the template (Sergeyeva et al. 2003;
Lin et al. 2008). An alternative to this crosslinking in situ may be polymer solution
A. Gómez-Caballero et al.