Design and Development of Plastic Antibodies against SARS-CoV-2 RBD based on Molecularly Imprinted Polymers that Inhibit In Vitro Virus Infection

Nanoscale ◽  
2021 ◽  
Author(s):  
Ortensia Ilaria Parisi ◽  
Marco Dattilo ◽  
Francesco Patitucci ◽  
Rocco Malivindi ◽  
Serena Delbue ◽  
...  

The present research study reports the development of plastic antibodies based on Molecularly Imprinted Polymers (MIPs) able to selectively bind a portion of the novel coronavirus SARS-CoV-2 spike protein. Indeed,...

Author(s):  
Ortensia Ilaria Parisi ◽  
Marco Dattilo ◽  
Francesco Patitucci ◽  
Rocco Malivindi ◽  
Vincenzo Pezzi ◽  
...  

Summary of the ideaOur idea is focused on the development of “monoclonal-type” plastic antibodies based on Molecularly Imprinted Polymers (MIPs) able to selectively bind a portion of the novel coronavirus SARS-CoV-2 spike protein to block its function and, thus, the infection process. Molecular Imprinting, indeed, represents a very promising and attractive technology for the synthesis of MIPs characterized by specific recognition abilities for a target molecule. Given these characteristics, MIPs can be considered tailor-made synthetic antibodies obtained by a templating process.In the present study, the developed imprinted polymeric nanoparticles were characterized in terms of particles size and distribution by Dynamic Light Scattering (DLS) and the imprinting effect and selectivity were investigated by performing binding experiments using the receptor-binding domain (RBD) of the novel coronavirus and the RBD of SARS-CoV spike protein, respectively. Finally, the hemocompatibility of the prepared MIP-based plastic antibodies was also evaluated.


Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1923
Author(s):  
Cheng-Chih Lin ◽  
Hung-Yin Lin ◽  
James L. Thomas ◽  
Jia-Xin Yu ◽  
Chien-Yu Lin ◽  
...  

Programmed death-ligand 1 protein (PD-L1) is often expressed in various malignant tumors; thus, it is an appropriate marker for targeted cancer therapies. Photodynamic therapy (PDT) uses light and photosensitizers to create singlet oxygen to kill cells. An important approach to PDT is the use of upconversion nanoparticles (UCNPs) to convert near-infrared (NIR) light, which penetrates tissues well, into visible light, allowing PDT to be effective at greater tissue depths. In this work, high-temperature pyrolysis was used to prepare both the core and shell of lanthanide-doped UCNPs with lithium yttrium tetrafluoride (LiYF4) to enhance the green luminescence. The photosensitizer Merocyanine 540 (MC540) was grafted onto the magnetic nanoparticles, and then one peptide sequence from PD-L1 was used as the template and imprinted onto poly(ethylene-co-vinyl alcohol) particles formed by precipitation in a non-solvent. UCNPs in the non-solvent bath were thus entrapped in the imprinted particles to generate composite nanoparticles for the targeting and photodynamic therapy of PD-L1 in tumor cells. Finally, the in vitro cytotoxicity of the nanoparticles in HepG2 human liver cancer cells was evaluated with the continuous administration of MC540/MNPs@MIPs/UCNPs under irradiation by an NIR laser. To understand the delivery of the UCNP-embedded molecularly imprinted polymers, the intrinsic and extrinsic pathways were also investigated.


2015 ◽  
Vol 1101 ◽  
pp. 256-260 ◽  
Author(s):  
Feng Feng ◽  
Zhi Min Liu ◽  
Zhi Gang Xu

β-Cyclodextrin shows good molecular recognition ability for its unique physical and chemical properties and suitable cavity structure. The selective recognition can be further improved if β-cyclodextrin combines with molecularly imprinted technique. In this paper, the novel β-cyclodextrin functional monomers were introduced. And the preparation and application of molecularly imprinted polymers based on β-cyclodextrin functional monomers were reviewed. The development trend of β-cyclodextrin molecularly imprinted polymers were also prospected.


Talanta ◽  
2020 ◽  
Vol 219 ◽  
pp. 121283
Author(s):  
Jia-Wei Zhang ◽  
Jia-Yuan He ◽  
Chong-Zhi Wang ◽  
Feng-Qing Yang ◽  
Lian-Di Zhou ◽  
...  

Polymers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 130 ◽  
Author(s):  
Yahui He ◽  
Shaomei Zeng ◽  
A. M. Abd El-Aty ◽  
Ahmet Hacımüftüoğlu ◽  
Woldemariam Kalekristos Yohannes ◽  
...  

Herein, a novel method for molecularly imprinted polymers (MIPs) using methacrylic acid functionalized beta-cyclodextrin (MAA-β-CD) monomer is presented, which was designed as a potential water-compatible composite for the controlled release of atropine (ATP). The molecularly imprinted microspheres with pH-sensitive characteristics were fabricated using thermally-initiated precipitation polymerization, employing ATP as a template molecule. The effects of different compounds and concentrations of cross-linking agents were systematically investigated. Uniform microspheres were obtained when the ratio between ATP, MAA-β-CD, and trimethylolpropane trimethacrylate (TRIM) was 1:4:20 (mol/mol/mol) in polymerization system. The ATP loading equilibrium data was best suited to the Freundlich and Langmuir isotherm models. The in vitro drug release study was assessed under simulated oral administration conditions (pH 1.5 and 7.4). The potential usefulness of MIPs as drug delivery devices are much better than non-molecularly imprinted polymers (NIPs). The study shows that the prepared polymers are a pH stimuli-responsive system, which controlled the release of ATP, indicating the potential applications in the field of drug delivery.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Mihkel Örd ◽  
Ilona Faustova ◽  
Mart Loog

Abstract The Spike protein of the novel coronavirus SARS-CoV2 contains an insertion 680SPRRAR↓SV687 forming a cleavage motif RxxR for furin-like enzymes at the boundary of S1/S2 subunits. Cleavage at S1/S2 is important for efficient viral entry into target cells. The insertion is absent in other CoV-s of the same clade, including SARS-CoV1 that caused the 2003 outbreak. However, an analogous cleavage motif was present at S1/S2 of the Spike protein of the more distant Middle East Respiratory Syndrome coronavirus MERS-CoV. We show that a crucial third arginine at the left middle position, comprising a motif RRxR is required for furin recognition in vitro, while the general motif RxxR in common with MERS-CoV is not sufficient for cleavage. Further, we describe a surprising finding that the two serines at the edges of the insert SPRRAR↓SV can be efficiently phosphorylated by proline-directed and basophilic protein kinases. Both phosphorylations switch off furin’s ability to cleave the site. Although phospho-regulation of secreted proteins is still poorly understood, further studies, supported by a recent report of ten in vivo phosphorylated sites in the Spike protein of SARS-CoV2, could potentially uncover important novel regulatory mechanisms for SARS-CoV2.


The Analyst ◽  
2018 ◽  
Vol 143 (9) ◽  
pp. 2002-2007 ◽  
Author(s):  
J. W. Lowdon ◽  
S. M. O. Alkirkit ◽  
R. E. Mewis ◽  
D. Fulton ◽  
C. E. Banks ◽  
...  

The first developed Molecularly Imprinted Polymers (MIPs) for the specific detection of methoxphenidine (MXP) and its regioisomers.


Pharmaceutics ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 41 ◽  
Author(s):  
Ortensia Ilaria Parisi ◽  
Mariarosa Ruffo ◽  
Rocco Malivindi ◽  
Anna Francesca Vattimo ◽  
Vincenzo Pezzi ◽  
...  

Cytotoxic agents that are used conventionally in cancer therapy present limitations that affect their efficacy and safety profile, leading to serious adverse effects. In the aim to overcome these drawbacks, different approaches have been investigated and, among them, theranostics is attracting interest. This new field of medicine combines diagnosis with targeted therapy; therefore, the aim of this study was the preparation and characterization of Molecularly Imprinted Polymers (MIPs) selective for the anticancer drug Sunitinib (SUT) for the development of a novel theranostic system that is able to integrate the drug controlled release ability of MIPs with Rhodamine 6G as a fluorescent marker. MIPs were synthesized by precipitation polymerization and then functionalized with Rhodamine 6G by radical grafting. The obtained polymeric particles were characterized in terms of particles size and distribution, ξ-potential and fluorescent, and hydrophilic properties. Moreover, adsorption isotherms and kinetics and in vitro release properties were also investigated. The obtained binding data confirmed the selective recognition properties of MIP, revealing that SUT adsorption better fitted the Langmuir model, while the adsorption process followed the pseudo-first order kinetic model. Finally, the in vitro release studies highlighted the SUT controlled release behavior of MIP, which was well fitted with the Ritger-Peppas kinetic model. Therefore, the synthesized fluorescent MIP represents a promising material for the development of a theranostic platform for Sunitinib controlled release and self-monitoring in cancer therapy.


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