State Key Laboratory of Organic-Inorganic Composites, International Joint Bioenergy Laboratory of Ministry of Education, National Energy Research and Development Center for Biorefinery, Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, 100029, China.
Clinical Laboratory, China-Japan Friendship Hospital, Beijing, 100029, China.
Adv Healthc Mater. 2024 Oct;13(27):e2400290. doi: 10.1002/adhm.202400290. Epub 2024 Jul 17.
Molecularly imprinted polymers (MIPs) show significant promise as effective alternatives to antibodies in disease diagnosis and therapy. However, the challenging process of screening extensive libraries of monomer combinations and synthesis conditions to identify formulations with enhanced selectivity and affinity presents a notable time constraint. The need for expedient methods becomes clear in accelerating the strategic development of MIPs tailored for precise molecular recognition purposes. In this study, an innovative high-throughput screening methodology designed to identify the optimal MIP formulation for targeting tumors is presented. Employing a microtiter plate format, over 100 polymer syntheses are conducted, incorporating diverse combinations of functional monomers. Evaluation of binding performance utilizes fluorescence-based assays, focusing on an epitope of the epidermal growth factor receptor (EGFR). Through this meticulously structured screening process, synthesis conditions that produced MIP nanoparticles exhibiting substantial specificity for EGFR targeting (K = 10 m) are identified. These "bionic antibodies" demonstrate selective recognition of cancer cells in whole blood samples, even at concentrations as low as 5 cells mL. Further validation through fluorescent imaging confirms the tumor-specific localization of the MIPs in vivo. This highly efficient screening approach facilitates the strategic synthesis of imprinted polymers functioning as precision bioprobes.
分子印迹聚合物（MIPs）作为抗体在疾病诊断和治疗中的有效替代品具有重要意义。然而，筛选大量单体组合和合成条件库以确定具有增强选择性和亲和力的配方是一个具有挑战性的过程，这对时间提出了明显的限制。在加速针对精确分子识别目的的 MIP 定制的战略开发中，需要快速方法变得很明显。在这项研究中，提出了一种用于鉴定针对肿瘤的最佳 MIP 配方的创新高通量筛选方法。采用微孔板格式，进行了超过 100 次聚合物合成，其中包含各种功能单体的组合。使用基于荧光的测定法评估结合性能，重点是表皮生长因子受体（EGFR）的表位。通过这种精心设计的筛选过程，确定了合成条件，这些条件产生了对 EGFR 靶向具有显著特异性的 MIP 纳米颗粒（K = 10 m）。这些“仿生抗体”在全血样本中表现出对癌细胞的选择性识别，即使在低至 5 个细胞 mL 的浓度下也是如此。通过荧光成像进一步验证证实了 MIP 在体内的肿瘤特异性定位。这种高效的筛选方法促进了作为精密生物探针的印迹聚合物的战略合成。
