LDL is a soluble complex formed by noncovalent interactions between lipids and proteins. Triglycerides and cholesterol comprise the central portion of the LDL, and the LDL is encased in an outer layer of phospholipids [1,2]. The perhydrocyclopentanophenanthrene structure of cholesterol limits its efficient degradation in human cells, making dietary cholesterol is considered to have an increased cardiovascular disease (CVD) risk [3]. Meanwhile, unregulated cholesterol levels could associate with LDL [4]. The amount of intact cholesterol in LDL is measured by Low-density lipoprotein cholesterol (LDLC). As a risk indicator and therapeutic target for hyperlipidemia, LDLC has now been the main lipid marker for determining cardiovascular diseases such as atherosclerosis. Furthermore, the majority of current guidelines also state that LDLC has emerged as a prominent candidate for initiating and tailoring modifying lipid-lowering therapies. Various methods of lowering LDLC have been well studied, such as lifestyle changes, medication therapy, intestinal bypass surgery, and lipid separation [5,6]. Nevertheless, order to overcome the inadequacies of the conventional approaches, for instance their high expense, laborious process, poor selectivity, and so forth, researchers are still in high demand to investigate a green, straightforward, and effective approach for the identification and extraction of LDL and its cholesterol.

Surface molecularly imprinted technology (SMIT) is biomimetic approach to selectively extraction and separation analytes of interest, eliminating the limitations via the straightforward creation of tailored imprinted sites on the substrate surface, thereby establishing precise cavities complementary to the goal molecule in phrases of form, size, three-dimensional structure and chemical capability [7,8]. The imprinting process is typically based on the attachment of suitable monomers containing functional groups to a template molecule via certain interactions [9]. Correspondingly, surface molecularly imprinted polymer (SMIPs) have specific spatial structures and chemical groups in the imprinted layer which are templated to match the target molecule [10]. SMIPs feature the merits of excellent selectivity, satisfactory loading capacity, fast transfer rate, low template leakage and promising stability, which enable them to selectively recognize and enrich target molecules [11], [12], [13], such as environmental pollutants [14,15], drugs [16,17] and proteins [18,19]. Numerous studies have applied SMIPs within the context of solid-phase extraction. And SMIPs show the most potential application in the field of sample analysis. Studies have consistently demonstrated the effectiveness of SMIPs in reducing complex matrix effects [8]. Currently, nanomaterials with various structures, consisting of consisting of silica nanospheres, graphene oxide, iron oxide, and so on, are used as carriers for surface imprinting [20]. Nevertheless, with the rapid development and extensive utilization, SMIPs face the additional challenge of satisfying the requirements toward green sustainability. With the recognition of the environmental challenges associated with unsustainable SMIPs, a new aspect of SMIPs termed “green SMIPs” has developed emerged and evolved.

Polydopamine (PDA) is a melanin-like material obtained by self-polymerization and self-oxidation of dopamine (DA) which acts as a "bioglue", and DA can form PDA on the surface of practically any material [21,22]. The satisfactory colloidal stability and biodegradability of PDA, as well as the lack of long-term toxicity, have made PDA exhibit substantial potential as an emerging material for SMIPs in the food field [23]. Recently, diverse proteins including hemoglobin, lysozyme, and horseradish peroxidase have been used as templates to fabricate SMIPs using PDA as a functional polymer monomer [24].

On the basis of these investigations, a unique sandwich-structured molecularly imprinted porous polydopamine nanosphere (PPDA-MIPs) for LDL separation is developed, which also improves the adsorption selectivity for “bad cholesterol” comprehensively. After determining the chemical composition and morphological characteristics of the prepared imprinted polymers, the isothermal adsorption behavior, selectivity as well as recyclability of PPDA-MIPs are evaluated and optimized by static equilibrium experiments in detail. Additionally, the applicability of PPDA-MIPs is assessed by successful separation of LDLC from the goat serum sample, which confirms the immense capability and potential promise of their use in bioanalysis.