Introduction

The molecular imprinting method is widely used in polymer science for the synthesis of Molecularly Imprinted Polymers (MIPs) [1,2,3,4,5]. The pre-organizational structure is formed with a target molecule and a functional monomer for the preparation of MIPs. The polymerization then continues with a crosslinking monomer and a suitable solvent. The polymerization could be performed through different methods such as electricity, thermal polymerization, and UV light polymerization. Sometimes, a chemical such as initiator can be required for different situations. When the polymerization steps are finished, the imprinted target molecules are removed from the polymer structure via desorption solutions. Thus, the polymer is obtained as three dimensional polymer specific target molecule. This polymer structure has the recognition cavities completely in chemical functionality, shape and size as the target molecule. Generally, non-covalent and covalent bonding process direct the molecular recognition event between the target molecules and functional monomer. The non-covalent bonding interaction event is mostly opted because of appropriate binding-rebinding case [6,7,8,9,10,11] (Fig. 1).

Fig. 1
figure 1

Schematization of MIP formation

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Due to the 3D recognition with high sensitivity and selectivity [12] features of MIPs, significant research has been conducted in different fields for the advancement of MIPs and have displayed perfect potential in different areas. MIPs have been applied in implementations such as drug delivery (DD) [13, 14], separation and purification [15], sensors/biosensors [16], catalytic applications [17, 18], detection of some important proteins and biomolecules [19,20,21].

The pharmaceutical and biomedical sectors have been faced with recent challenges that necessitate the creation of novel analytical techniques [22]. Simultaneous diagnostic techniques combined with targeted therapy offer a theranostic strategy, which serves as a valuable tool in the realm of personalized medicine. This approach is considered to be one of the most promising trends in contemporary medical practice. In addition to selecting the correct medication for treatment, significant emphasis is placed on the advancement of efficient drug delivery systems (DDS). Within the realm of drug carrier production, MIPs stand out as a promising option with immense potential for application in theranostics [23].

Bio-applied MIPs are synthetic materials designed to mimic the recognition sites found in biological systems. These materials are specifically engineered to exhibit high sensitivity and selectivity in detecting analytes. MIPs, which are specifically engineered for the purpose of biomarker analysis in biofluids, possess the capability to greatly assist in patient diagnostics at the point-of-care, facilitating self-health monitoring and management. Recent studies in this field have made significant progress by combining materials science and biology, resulting in the emergence of various polymerization synthesis techniques specifically designed for the bio-application of MIPs [24].

There has been a significant increase in the application of MIPs with biomacromolecules in recent years. MIPs produced by using biomolecules as template molecules are called "plastic antibodies" or "artificial receptors". It is cheaper and easier to produce and has emerged as an alternative to antibodies [25].

In this review, we examined important developments for MIP applications in the following sections. The main aim here is to address MIP issues that address in fields of biochemistry, biomedical and biotechnology such as DD, cell recognition, enzyme applications, in vivo applications, applications for some important biomolecules. Some template molecules used for MIPs in 3B areas were shown in Fig. 2.

Fig. 2
figure 2

Some template molecules used for MIPs in 3B areas

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Drug delivery

The conventional pharmaceutical formulations by a majority have not compensated the desires of modern pharmacotherapy. Therefore, numerous studies have been conducted to improve new drug delivery systems convenient for such a aim. These attempts were accelerated by great progress in both technology and material science [26].

Polymeric DDS is extensively employed in DD. Even if these systems are useful agents for efficient drug delivery, these systems occasionally display burst release of drug owing to inconvenient severe circumstances of around and human body. However, the usage of drug delivery systems based on MIPs has shown better efficiency for DD and thus, its applications in drug delivery systems are too much.

The improved affinity of the template molecule to the functional monomer, thus enhancing the staying period of the drug, superior drug loading performance of an MIP structure, their excellent stability and endurance against heavy circumstances, simple arrangement of the crosslinking talent of the polymer, the usage of non-covalent/covalent interactions are some beneficial properties of MIPs [1].

The loading performance of various DDSs may substantially impact treatment performance and/or dosing in different techniques, mainly an alter in pharmacokinetic and pharmacodynamic property [27, 28]. For polymer-originated DDSs, drug molecules are usually spreaded inside a polymer matrix structures/behind a polymer membrane, intended at releasing drugs at a controlled ratio or with specific physiological circumstances. In this instance, different side/disadvantageouses of the drug may be decreased or even obviously overcome these problems [29]. However, a burst releasing of drug is usually happened in traditional polymeric tools and thus resulting in possible heavy outcomes for the patients such as toxicity troubles and unwanted side influences gave rise to by momentarily high-drug dosage [30].

MIPs are extremely important tools in drug delivery due to their application versatility, high loading capacities, desired target (stereo) selectivity. Excellent drug loadings with conventional nonimprinted polymeric systems result in lower dosages and thus improved safety profiles with reduced susceptibility to adverse reactions [31]. Despite their low immunogenic characteristics, the biocompatibility of MIPs remains a controversial issue. Although it is generally approved that MIPs have excellent biocompatibility, their long-term impacts in living organisms have not yet been fully examined [32, 33] (Fig. 3).

Fig. 3
figure 3

Polymerization and template removal steps of MIP structure

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Up to now, despite of improving polymeric tools have been advanced, various fundamental knowledge gaps in the context of toxicity, unstability of physicochemical properties and lack of responsiveness to stimuli agents have been handled in a very limited rate, thus restring also practical implementation [34,35,36]. Averagely, only one of the 5000 polymer-originated DDSs that subjects pre-clinical studies becomes an confirmed dosage form after more or less 10 years (from the first opinion to the marketing endorsement) [29, 37]. MIPs are up-and-coming materials in the forming of developed drug delivery tools since they could ensure advanced delivery profiles, longer release durations and extended stay of the drug (Table 1).

Table 1 Some DDS studies related to MIPs
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For the ultimate drug delivery system design or carrier, advanced drug loading performance and controlled drug releasing, as well as biocompatibility and biodegradability are extremely important. MIP has the advantage because of its biocompatibility and biodegradable main components (functional monomer and crosslinker) [48].

In a very different example, amphiphilic lipopolysaccharides derived from P. aeruginosa were utilized as a template material for the arranging of nanoMIPs using the reverse emulsion technique for theranostic purposes [49]. Fluorescent nanoMIP constructs labeled with IR-783 proved selective recognition of bacteria targeted for keratitis and meningitis. P. aeruginosa-targeted nanoMIPs encapsulated with a photosensitive structure (methylene blue) have been utilized in in vitro photodynamic therapy. It was revealed that nanoMIPs showed higher activity against bacteria after interaction with the laser. In addition, this nanoMIP formulation was found to be very stable and performed similarly even after 6 months of storage.

MIP is emerging as a very promising method for controlled release and targeted delivery system with certain advantages. Because it is in its infancy, extensive and deeper research is required to improve a both safe and operative MIP-DDS. Migrations from the bench to clinical applications and large-scale fabrication are key points for successful clinical implementation of MIP. Despite this, there is good practice expectation in the scientific community in drug delivery (especially the targeted diagnosis and treatment of tumors). In short, with a comprehensive study of MIPs in carrier systems, MIP-DDS will act a significant role for the therapy of diseases [50].

MIP has gained significant attention as a potential drug carrier due to its unique benefits, particularly in the areas of sustained release, controlled release, and targeted release system. However, despite being in its nascent phase, there is a lack of extensive and thorough research to establish a secure and efficient MIP-DDS. To begin with, it is imperative to conduct further research on the stability, biocompatibility, and toxicity of MIP, particularly in the context of long-term toxicity, when utilized in intravenous drug delivery systems. Additionally, the majority of molecularly imprinted polymers (MIPs) are produced in organic solvents, necessitating strict regulation of any remaining organic solvents. Furthermore, there is a deficiency in MIP synthesis for biological macromolecules like water-soluble drugs and polypeptides. Moreover, there is a requirement for the advancement of superior components, such as functional monomers, in the creation of molecularly imprinted polymers to cater to clinical uses. Computerized high-throughput screening methods can be demanded. Ultimately, the transition from laboratory experimentation to practical use in medical settings and the achievement of large-scale manufacturing pose significant challenges that must be addressed to effectively incorporate MIP in clinical practice. Despite the aforementioned limitations of MIP, its ability to control release and target specific areas still offers notable benefits in drug delivery and holds great potential for application, particularly in the targeted diagnosis and treatment of tumors. In summary, as molecular imprinting technology continues to advance and further research is conducted on MIP in drug delivery systems, MIP-DDS is poised to assume a crucial role in disease treatment as a promising drug delivery system [50].

MIPs for cell recognition

Cells are one of the toughest target molecules in molecular imprinting processes [51]. Among the most successful examples where cell-imprinted MIP systems are utilized for cell separation is the capture and separation of bacteria. The potential to separate different bacterial species by electrophoresis was demonstrated in 2006 [52].

The microcontact stamping approach is the most common discovered method for creating MIPs utilizing whole cells as templates [53]. Target cells are deposited on a planar solid support. It covers coating it with monomers or a soft polymer such as pre-polymerized polyurethane. Next, the polymer cures, and the cells are sandwiched between the support layer and the polymer formed. It has been reported in the literature that whole cell MIPs exhibit shapes, sizes and functional selectivities for cell templates [54, 55]. A wide variety of target molecules and materials (bacteria, yeast, mammalian cells) have been imprinted by utilizing with this way [51].

The whole-cell imprinting way generate a shape recognition substance which may not be optimum if the aim is to recognize a specific kind of human cell. Because of the high plasticity of mammalian cells, shape recognition alone may not always provide the discrimination necessary for success. On the other hand, MIPs designed for cell recognition for in vivo purposes might have nanometer dimensions for diffusion within the vessels and lymphatic system and intracellular space, while imprint of a whole cell unavoidably is result in micrometer sizes [51].

The capacity of synthetic receptors for cell recognition remained unexplored for an extended period. However, the past ten years have seen significant advancements in MIPs for precise cell recognition. Presently, the effectiveness of MIPs in facilitating cell recognition has been effectively showcased across various fields such as environmental monitoring, food safety, and public health. To facilitate MIP-mediated cell recognition, it is imperative to engineer MIPs that possess a discerning affinity for either particular cell membrane molecules or the collective composition of the cell membrane. Clearly, the difficulties encountered in the development and creation of MIPs for cell recognition are significantly greater compared to conventional applications. Thankfully, in recent times, there has been a consistent advancement in MIP-mediated cell recognition. In addition to investigating novel cell membrane molecules for imprinting, it would be highly beneficial to enhance the effectiveness of MIP-mediated cell recognition in vivo, as this is an important aspect for bio-related applications. On the whole, MIP-mediated cell recognition has demonstrated its significance. These chemically engineered receptors are now nearing the level of functionality exhibited by their natural counterparts. It is widely believed that MIP-based synthetic receptors will progressively contribute to bridging the divide between biological science and chemical science [12].

Applications

Cell concentration/separation

Imprinted gel granules were synthesized on the gel synthesized from acrylamide and N,N'-methylenebisacrylamide with E. coli (template molecule), and a distinction was observed between E. coli MRE-600 and E. coli BL21 due to the presence of template molecule by electrophoretic migration. Specific capture of Deinococcus radiodurans, E. coli, Sphaerotilus natans and Bacillus subtilis using imprinted films was performed by Cohen et al. [56].

Tissue engineering

Understanding of microenvironmental models for cell differentiation is limited. Therefore, it can also be difficult to envision and design tissue scaffolds. In this regard, the molecular imprinting process has the possibility to provide a solution to this issue. An important aspect of molecular imprinting in the case of cell differentiation is that it has a relatively easy technique for generating topographic cell fingerprints in directed tissue growth. It should also be noted that there is the possibility of using clinical MIPs to amplify cell populations [51].

Imaging applications

Drug delivery and imaging become highly interconnected when it comes to safety issues and targeted delivery to a particular cell/organ. Especially in imaging applications, fluorescent, magnetic or positron emission of nanoMIPs is expected [51]. For the imaging field, nanostructures have molecularly imprinted shell are preferably used [57].

Asadi et al. improved a MIP originated material both imaging and therapy hybrid material. It is produced by a fructose-based biodegradable crosslinking agent. It was presented to the literature as brain-targeted MIP production. This study also has the feature of being one of the first studies in this field [58].

Thurston et al. magnetic Fe3O4 shell structure completed the polymerization with template molecule olanzapine (an antipsychotic drug), monomer and crosslinker (double-acting fructose). As a result of the observations, it was reported that the magnetic field facilitated the accumulation of the carrier near the target tissue. The degradation of the MIP structure may be utilized for an energy source for brain cells when there is a high fructose concentration compared to glucose. The imaging feature was created with fluorescein isothiocyanate loaded on the silica structure with pores in the surface regions of Fe3O4 nanostructures [59].

In another study, a therapeutic study on MIP photothermal treatment was applied for the first time. Here, gold nanorods were utilized as the core plasmonic nanomaterial. The template material was sialic acid, and boronate affinity-based surface printing was applied. Notably, sialic acid-specific gold nanorods deposited in the tumor region. NIR based laser beam was applied to the tumor area for a while. Gold nanorods imprinted with sialic acid attached to the tumor absorbed the energy of light and converted it into heat. This heat then causes tumor ablation within several photothermal therapies. Thus, it leaves healthy tissues undamaged. For future implementations, NIR797 dye-doped sialic acid-imprinted gold nanorods hold an extremely important potential for targeted photothermal therapy-based treatments in cancer imaging [60].

Unlike multi-step immunostaining methods, MIP-based molecular recognition and imaging generally have a one-step process. MIP structures also have the possibility to be produced for different kinds of target molecules, from small molecules such as single amino acid/sugar to protein structures and even whole cell [57].

We are hopeful that MIP structures as plastic antibody structures have significant potential as bioimaging materials and have many still unexplored applications.

Applications enzyme imprinting

Molecular imprinting process is an efficient technique to form multifunctional binding spaces for molecules of plenty of various sizes. Due to their inherent advantages in molecular terms (inexpensive, high selectivity, good thermo-chemical stability, and especially no need for some biological protocols), they have become a viable method to mimic natural enzymes [61].

The selectivities of nanozymes may be increased considerably (up to 100 times) by coating them with a MIP layer. MIP forms specific binding cavities for the imprinted substrate so that other substrates are blocked from reaching the nanozyme surface and the imprinted molecules are able to be enriched. In this case, it can selectively access the catalytic core [62].

In order to create a catalytic system that is extremely efficient, it is crucial to carefully select appropriate functional monomers and accurately position them to enhance the binding of transition states. MIP-based biomimetic catalysts have demonstrated promising outcomes in various significant reactions. Despite the fact that the catalytic efficiency of current imprinted polymers remains relatively low in aqueous environments when compared to their natural biological counterparts, notable advancements have been achieved in downsizing imprinted particles, enhancing their solubility, and ensuring monodispersity to enhance mass transfer. Furthermore, some catalysts have proven effective even under harsh conditions, such as in the removal of contaminants from polluted water or soil samples. Subsequent advancements in this domain could potentially broaden the spectrum of natural enzymes that can be mimicked and may even extend the capabilities of imprinted catalysts to reactions that are not typically catalyzed by natural enzymes. An essential aspect that requires further exploration is gaining a deeper understanding and defining the mechanisms of reactions to more accurately replicate natural processes. It will be crucial to dedicate additional research efforts towards comprehending the factors that impact catalytic activity, especially the alterations in the properties of polymeric matrices in response to external stimuli. Anticipated future research in this area is poised to yield artificial catalytic systems that can be applied across a diverse array of practical applications [63].

The first catalytic MIP applications were directed toward stereo-controlled chemical reactions and enantioselective synthesis [63]. Although the artificial enzymes based on MIP made ready by such a technique may show excellent catalytic activity, there are still some barriers that restrict the higher activity, containing challenges in template elimination, slow transportation of substances inside and outside of polymer. The most important point is heterogeneity of binding sites giving rise to extensive binding affinity [64].

It is extremely important to prepare the artificial enzymes based on MIP both high catalytic activity and specific selectivity. Nanozymes are gaining increasing attention due to their superior features. The MIP/nanozyme binary association is an important threshold for developing artificial enzyme constructs. MIPs are used as selective adsorbents and specific recognition materials in important disciplines such as medicine, chemistry, biology, environment and food sciences. Besides being used as plastic antibodies, they can also be used as artificial enzymes called plastic enzymes. This route includes imprinting substrates, substrate analogs or structurally similar transition state molecules into the polymer structure to obtain cavities that are artificial active fields in catalytic reactions [61].

Wu et al. performed surface molecular imprinting on g-C3N4 (graphite carbon nitride) nanozymes for enhanced biosensing to demonstrate the photooxidase activity of graphite carbon nitride. It showed superior enzymatic activity upon irradiation of blue LEDs on g-C3N4. It has been shown that surface molecular imprinting on g-C3N4 may give rise to a very good enzymatic activity during colorimetric detection compared to bare g-C3N4, as well as improved substrate specificity [65] (Fig. 4)

Fig. 4
figure 4

Molecular imprinting on graphite carbon nitride nanozymes for enhanced biosensing [65]

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Tetracycline, one of the most well-known antibiotics, is extensively utilized in animal husbandry, aquaculture and in the therapy of human diseases. Since more than 60% of tetracycline cannot be absorbed, it is excreted directly in the form of urine and feces. This event poses a serious threat to the environment and living beings. For these reasons, monitoring of tetracycline is essential to ensure food safety and ecosystem health. Liu et al. developed molecularly imprinted areas on the Fe3O4 nanozyme surface and thus improved a colorimetric assay for the highly specific determination of tetracycline. The Fe3O4@MIP structure was specifically captured by the MIP shell in the presence of tetracycline. The Fe3O4@MIP construct, designed to exhibit a peroxidase-mimetic activity, was specifically captured by the MIP shell in the presence of tetracycline and partially blocked the spaces for substrate access, such that it did not cause the catalyzed chromogenic reaction of 3,3′,5,5′-tetramethylbenzidine. Thus, tetracycline was detected highly selective colorimetrically [66].

In another literature study, a boric acid functionalized pyrite nanozyme was presented and was utilized together with glycoprotein molecular controllable-oriented surface imprinted magnetic nanoparticles to compose a set of sandwich detection ways independent of biological macromolecules for the detection of glycoproteins in serum. Lastly, the sandwich detection technique is utilized to investigate transferrin and alkaline phosphatase in serum of liver cancer patients. Owing to the utilizing of this new nanozyme probe, which was easier to preserve than HRP, the detection time of this method had been highly shortened and the detection sensitivity also improved [67].

In vivo applications of MIPs

Although MIPs are widely used in in vitro and in vivo implementations remain challenging as not much is known about their long-term toxicity, biodegradability, biocompatibility, and distribution in liquids, MIPs are small and stable structures with well-defined features, and thus, they can be taken into account for therapeutic implementations. According to their imprinting process, MIPs are versatile, meaning that they can be quenched against different in vivo targets such as protein, glycan structures, or other moieties found in living organisms. MIP targeting is also increasing rapidly in drug delivery [68].

In one study, glycan-imprinted MIP structures were utilized as a therapy for breast cancer. A mouse model was used in this study. It has been observed that MIP structures inhibit cell proliferation and cause a decrease in tumor volume. The results obtained here showed that MIP constructs can be utilized as a new and effective cancer treatment [69].

The most important point in applications to be made in living systems is the low toxicity of nanostructures. In a nanoparticle, the core element determines properties that are extremely important for toxicity. The charge, size, and shape of the particle's surface directly affect cellular uptake and provide insight into how particles interact with organelles and biomolecules. Another point to note is that the toxicity of nanoparticles may differ for in vitro and in vivo applications [68, 70, 71]. While some studies in the literature have reported that fluorescent MIPs have no toxic effect [72], other studies have reported low toxicity [73, 74]. In another study, low toxicity was found in different model organisms such as mice or zebrafish [75, 76].

Applications of MIP structures, especially in living organisms, offer extremely important possibilities. The great usable potential of MIPs represents their use in imaging due to their high specificity and easy coupling with other probes.

MIPs possessing exceptional specificity and affinity are highly favored in the field of biomedical applications, particularly when there is a lack of reliable detection tools for specific cellular targets. A promising avenue for future exploration lies in the development of MIPs with dual functionalities, wherein cellular targeting is coupled with either drug delivery or the ability to modify cellular function. This innovative approach holds great potential for advancing targeted therapies and enhancing biomedical interventions [68].

MIP applications for some important biomolecules

The field of molecular imprinting has experienced significant growth in the past twenty years, particularly in its applications within biochemistry, biology, and medicine. Numerous publications within this field have highlighted the advancements made. Currently, there is a strong focus on researching and developing the applications of MIPs in biology and medicine at a small-scale level. MIPs offer synthetic recognition sites that can be customized for use in analytical, diagnostic, and drug delivery systems, thereby propelling the field of personalized medicine forward. The versatility of MIPs has contributed to their increasing popularity, as they can be utilized in various formats depending on the specific application. The synthesis of MIPs and their components offers a wide range of possibilities. Various MIP formats are available, ranging from simple polymeric films to more complex systems that include nanoparticles and core–shell molecularly imprinted nanoparticles. This flexibility allows for the customization of MIPs to suit a wide range of objectives. The MIP technique enables the creation of materials that mimic natural antibodies, with the added benefit of comparable or superior analytical performance in comparison with antibody-based assays. While antibodies are currently preferred in some applications, MIPs have shown excellent performance and have the potential to replace antibodies in certain scenarios. Natural antibodies often struggle to effectively target small or simple antigens due to limitations in specificity and sensitivity, whereas MIPs can be further refined and enhanced to emerge as the optimal choice for biosensing applications [77].

MIPs have become an alternative to biological recognition materials with their robust construction and ability to work in harsh environments [78].MIPs are designed materials that can mimic biological ligands and detect target molecule(s) both selectively and sensitively. In particular, given the challenges faced by researchers working with biomolecules, the MIP technique will prove to be extremely important materials for creating highly hopeful stable artificial receptors that will replace or accelerate biological matrices. The ease of synthesis, low cost, adaptability to the target molecule, and stability in harsh conditions make MIPs promising candidates as recognition vehicles for biological molecules [79].

Odabaşı et al., made ready cholesterol imprinted poly(2-hydroxyethyl methacrylate-methacryloyamidotryptophan) particles embedded composite membranes. Stigmasterol and estradiol were utilized as competitor molecules in selectivity experiments. Prepared membranes were 1.96 and 2.13 times more selective for cholesterol, respectively, as per to the competing molecules stigmasterol and estradiol [21] (Fig. 5).

Fig. 5
figure 5

Mechanism of formation of cholesterol imprinted membranes [21]

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N-acyl-homoserine-lactones (AHL), one of the main signaling molecules of gram-negative bacteria, can express pathogenic factors, and also the Quorum Sensing (QS) system can act a key role in being virus identification. AHLs are generated at very low concentrations and are hard to detect given general methods. Acet et al. N-hexanoyl-l-homoserine lactone (C6-HSL)-specific MIP membranes made ready on QCM chips and molecularly imprinted QCM chips were used for detection C6-HSL from aqueous medium with high sensitivity. The results were monitored with the aid of a QCM sensor. The highest C6-HSL adsorption on the printed QCM chip surface occurred at a concentration of 1000 ng/mL, pH 7.0. When the results obtained from the sensor were compared with the GC–MS results, the results were found to be correlated. At the same time, the synthesized polymers confirmed their sensitivity to C6-HSL in solution including competitor molecules [80].

Low limit of detection and specific affinity and high selectivity in protein rebinding is the most important parameters that show the performance of MIPs. [81]. Wang et al. [82] developed a MIP/SPR sensor chip for BSA detection. For this purpose, it was used the electropolymerization of (3-aminophenyl) boronic acid (3-APBA). The surface morphology of the printed and unprinted films was brightened with the help of SEM analysis. It has been observed that the MIP film has homogeneous nano dimensions. In addition, optimization and selectivity experiments were carried out for MIP/SPR sensors. LOD value was determined as 0.02 mg/mL.

Saylan et al. [83] improved a MIP/SPR sensor for detection hemoglobin. Here, hemoglobin (template molecule) was printed on an acrylamide nanofilm by utilizing the photopolymerization method. The synthesized MIP nanofilm surface was characterized with the aid of AFM and an ellipsometer. The SPR sensor demonstrated linear concentration range (between 0.5 μg/mL and 1.0 mg/mL for hemoglobin detection with an LOD value of 0.35 μg/mL.)

l-asparagine (l-Asn) is a non-essential amino acid type that is needed for the synthesis of some important cellular protein for normal human cells and is found in the metabolic control of cell functions in nerve and brain tissue. Acet et al. were fabricated l-Asn imprinted membranes (l-Asn-MIPs) by molecular imprinting technique with the aim of selective and efficient removal of l-Asn. The surface of the imprinted and the nonimprinted membranes were characterized by using the SEM device (Fig. 6). The surface of the imprinted membrane was found to have rougher surfaces (Fig. 6A) than the surface of the nonimprinted membrane (Fig. 6B). The highest l-Asn adsorption performance was made decision as 408.2 mg/g at pH: 7.2, 24 °C. The effect of pH, selectivity and reusability of the l-Asn-MIPs toward l-Asn were determined via l-asparaginase enzyme activity measurement. The selectivity tests were tested by utilizing two different ternary mixtures. The results demonstrated that the l-Asn-MIP membranes have a high selectivity to l-Asn [84].

Fig. 6
figure 6

SEM photos of A l-Asn-MIP and B nonimprinted membranes [84]

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Biomarkers are indicators for biological processes that can precisely indicate and appraise the pathogenesis or pharmacological response to therapeutic interventions. Examples of biomarkers utilized for various aims are lipids, proteins, imaging models, genomic, metabolomic/proteomic models [85]. Biomarkers help to indicate a specific physical trait or a measurable biological change in the body associated with a disease/health condition [86]. Delays in some outcomes can result in significant morbidity and mortality. Therefore, there is an extremely important need for fast, inexpensive and at the same time sensitive analytical techniques. MIPs could play a role in solving these problems, as they are synthetic materials that can mimic biorecognition well enough to be termed "plastic antibodies" [68, 87].

Lately, there have been an rise in the number of studies on the usage of MIPs as a biomarker, as it has the capacity to be a diagnostic tool, which is extremely sensitive, harmless, fast and low cost [88].

A sensor imprinted for carcinogenic embryonic antigen, a colorectal cancer biomarker, was presented in one study. In this study, a hybrid system consisting of a voltaic cell consisting of a MIP-based sensing system and a dye-sensitized solar cell was established. The selectivity of sensor was assessed in a 3-electrode step by electrochemical impedance spectroscopy and square-wave voltammetry. The analytical performance in carcinogenic embryonic antigen detection turned out to be similar to the results of a normal biosensor. Thus, using the MIP structure on the electrode is important for detectability and reproducibility [89].

An interesting and very practical feature of some sensors prepared with MIP is the possibility of distinguishing between a pair of enantiomer molecules [3]. Enantiomer molecules can have similar, different or even opposite biological behavior in chiral mediums because of different channels of interaction with receptors/enzymes [90]. As an example, for the radiopharmaceutical field, [11C] l-methionine is an accepted tracer for brain tumor diagnostics. However, [11C] d-methionine does not have this property. The enantioseparation of these two compounds is a very important issue [91]. Much of the recent literature has turned to the use of chirality-based molecularly imprinted polymers as the separation method for HPLC analysis [3]. In a study in the literature, an enantioselective sensor was made ready on the surface of a quartz crystal microbalance (QCM). MIPs have been used to identified thalidomide and its (R)-enantiomers together with infrared spectroscopy and atomic force microscopy [92]. After the MIPs were prepared and the template molecule was extracted, the electrode was utilized for recognition. The outcomes show that the analyte of interest, the template molecule, and its enantiomers have a different binding energy when interacting with chiral MIP vacancies. This method has also provided significant information about the mechanism of stereochemistry for biological systems to the literature.

Gutiérrez-Climente et al. prepared chiral MIP nanoparticle structures by precipitation polymerization technique. These constructs were used to prepare an enantioselective sensor on a polyvinyl chloride (PVC) membrane [93]. Prepared membranes were produced by dissolving PVC in tetrahydrofuran (THF). After these processes, plasticizer was added to the solution together with chiral MIP nanoparticle particles. Then, a certain amount of this prepared membrane was united with the ion selective electrode and utilized in the next experimental stages. This prepared selective potentiometric sensor was utilized to recognize the S enantiomer of citalopram as an antidepressant drug in urine samples. This study also revealed some notable factors that require to be optimized for sensor performance such as the number of nanoparticles, the kind and amount of plasticizer, and the concentration of the internal reference solution. It has emerged as a fast, inexpensive and easy-to-use technique. Fourier transform infrared spectroscopy test was used to prove the porous structures in the membrane network compared to the unprinted membrane and pure S-citalopram. This technique has been shown to have high selectivity and reliable outcomes in complex urine matrices.

Conclusion and future perspectives

Many years have passed since the synthesis of MIPs. Compared to the past, imprinting techniques were different and not suitable for cellular applications. Developments and studies in recent years have shown serious advances in promising imprinting techniques. MIPs are molecules with high stability even under extreme conditions, making them a special class of polymers. The fact that MIPs can be functionalized and produced in a short time makes them unique. Generation of MIP constructs also relies upon template selection, which may be any biological construct small enough to form a specific and selective template utilized for different implementations. Recognition of cells and molecules is extremely important for the biomedical field. There is also the possibility that if important approaches such as the suppression of cells, cell membranes and microorganisms are successful, MIPs could be extended for applications in diagnostics and personalized medicine and even certain diseases such as cancer. For the future, dual/multifunctional MIPs for DDSs are likely to be seen in DDSs.

It is one of the most important components of the material produced and its environmental friendliness. The utilization of MIP sorbents as readily applicable final products in analytical processes is undeniably an exemplification of green analytical chemistry. The consideration of potential adverse effects on the environment, the series of procedures required to acquire an appropriate absorbent material with exceptional selectivity holds significant importance [94].

The issue of pharmaceuticals being found in post-treatment wastewater effluents is a major concern in the realm of wastewater management and public health. Both governments and the scientific communities are actively striving to address this pressing issue by seeking effective solutions. Nevertheless, the continuous requirement for the development of pharmaceutical monitoring techniques that are capable of providing rapid, timely, and sensitive responses remains a crucial necessity [95].

Molecular imprinting technology is a promising field that has gained traction in various industries due to its specificity in target recognition, high efficiency, stability, and eco-friendliness. MIPs, also referred to as 'artificial receptors,' exhibit properties akin to natural receptors as a biomimetic material. By incorporating MIPs into sensors, the selectivity of target recognition can be significantly enhanced. MIPs are particularly suitable for the pretreatment and analysis of trace substances in complex matrix samples. Currently, a range of sensors have been developed in conjunction with MIPs to detect and identify trace compounds, biological macromolecules, or other substances using optical, electrochemical, and piezoelectric sensors. Smartphones, equipped with built-in sensors and advanced digital imaging capabilities, offer a unique platform for on-the-go and real-time sensing requirements. The development of MIP sensors integrated with smartphones is anticipated to pave the way for a new research avenue in the future [96].