A High‐Throughput Screening Strategy for Synthesizing Molecularly Imprinted Polymer Nanoparticles Selectively Targeting Tumors

Abstract 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 D = 10 −12 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 −1 . 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.