Protein-derived biomaterials are currently underrated as building blocks in molecular imprinting, even though they offer several benefits, such as biocompatibility and safe biodegradability. Gelatin is a biopolymer that can be easily modified with pendant double bonds for polymerization, making it suitable for tissue engineering and biofabrication. In this study, we used gelatin methacryloyl (GelMA) as a building block combined with molecular imprinting technology to create an original class of bioinspired nanotraps specifically capable of sequestering the proinflammatory cytokine interleukin-6 (IL-6). The stability in solution, biocompatibility, and biodegradability of the nanotraps were assessed. The nanotraps were selective and specific for IL-6, showing nanomolar affinity and, when tested in vitro on an inflammation cell model, sequestered IL-6 with a dose-response relationship. Overall, our study shows that protein chemistry-driven molecular imprinting could become more widely used to devise biocompatible functional nanomaterials.

Currently, optical sensors based on molecularly imprinted polymers (MIPs) have been attracting significant interest. MIP sensing relies on the combination of the MIP’s selective capability, which is conveyed to the polymeric material by a template-assisted synthesis, with optical techniques that offer exquisite sensitivity. In this work, we devised an MIP nanoparticle optical sensor for the ultralow detection of serum albumin through time-resolved fluorescence spectroscopy. The Fluo-nanoMIPs (∅~120 nm) were synthetized using fluorescein-O-methacrylate (0.1×, 1×, 10× mol:mol versus template) as an organic fluorescent reporter. The ability of 0.1× and 1×Fluo-nanoMIPs to bind albumin (15 fM–150 nM) was confirmed by fluorescence intensity analyses and isothermal titration calorimetry. The apparent dissociation constant (K_app) was 30 pM. Conversely, the 10× fluorophore content did not enable monitoring binding. Then, the time-resolved fluorescence spectroscopy of the nanosensors was studied. The 1×Fluo-nanoMIPs showed a decrease in fluorescence lifetime upon binding to albumin (100 fM–150 nM), K_app = 28 pM, linear dynamic range 3.0–83.5 pM, limit of detection (LOD) 1.26 pM. Selectivity was confirmed testing 1×Fluo-nanoMIPs against competitor proteins. Finally, as a proof of concept, the nanosensors demonstrated detection of the albumin (1.5 nM) spiked in wine samples, suggesting a possible scaling up of the method in monitoring allergens in wines.

In this work, we report the development of a highly sensitive optical sensor for the detection of cardiac troponin I (cTnI), a key biomarker for early-stage myocardial infarction diagnosis. The sensor combines castor oil-derived biomimetic receptors, called GreenNanoMIPs and prepared via the molecular imprinting technology using as a template an epitope of cTnI (i.e., the NR10 peptide), with a portable multimode plastic optical fiber surface plasmon resonance (POF-SPR) transducer. For sensing, gold SPR chips were functionalized with GreenNanoMIPs as proven by refractive index changes and confirmed by means of XPS. Binding experiments demonstrated the cTnI_nanoMIP-SPR sensor’s ability to detect both the NR10 peptide epitope and the full-length cTnI protein within minutes (t = 10 min), with high sensitivity and selectivity in buffer and serum matrices. The cTnI_nanoMIP-SPR showed an LOD of 3.53 × 10⁻¹⁵ M, with a linearity range of 1 pM–100 pM, outperforming previously reported sensor platforms and making it a promising tool for early-stage myocardial infarction detection.

The rapid and accurate detection of SARS-CoV-2 biomarkers remains a critical requirement for effective outbreak control and decentralized diagnostics. Although RT-PCR is the current gold standard, its reliance on centralized laboratories and long processing times limits its applicability in point-of-care settings. In this context, optical biosensing platforms based on surface plasmon resonance (SPR) offer attractive features, including label-free, real-time, and quantitative detection. This study explores the use of synthetic receptors for the highly sensitive detection of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Specifically, soft molecularly imprinted polymer nanoparticles (nanoMIPs) were employed as synthetic receptors and integrated into a high-sensitivity, portable plasmonic platform based on a D-shaped plastic optical fiber (POF) SPR sensor. The nanoMIPs were selectively imprinted against the RBD, characterized by Dynamic Light Scattering (DLS), Isothermal Titration Calorimetry (ITC), and Scanning Electron Microscopy (SEM) to confirm nanoMIPs size, binding properties, and surface morphology. Next, the nanoMIPs were immobilized onto a gold-coated sensing surface, enabling enhanced specificity, affinity, and signal amplification compared to conventional biological recognition elements. The resulting RBD-SPR-nanoMIPs sensor demonstrated promising analytical performance, exhibiting high selectivity against potentially interfering proteins and an anticipated sensitivity suitable for RBD detection at femtomolar concentrations. The inherent stability of nanoMIPs suggests the potential for reusable SPR sensing platforms, paving the way for next-generation synthetic receptor-based plasmonic biosensors.