Site-specific post-imprinting modification of molecularly imprinted polymer nanocavities with a modifiable functional monomer for prostate cancer biomarker recognition

Sci Technol Adv Mater. 2019 Apr 1;20(1):305-312. doi: 10.1080/14686996.2019.1583495. eCollection 2019.


Recognition of glycans of glycoproteins using biotic materials such as antibodies is challenging due to lack of antigenicity. Polymeric materials suitable for the molecular recognition of glycoproteins have attracted considerable attention. In this study, we aimed to develop abiotic molecular materials for the recognition of prostate-specific antigen (PSA), a known biomarker for prostate cancer. We used a non-covalent bonding-based molecular imprinting technique to introduce post-imprinting poly(ethylene glycol)-based capping agent into a low-affinity recognition cavity. Details of the binding properties of these groups were investigated to optimize their affinity and selectivity for PSA. Molecularly imprinted polymers (MIPs) were prepared using a bottom-up approach based on surface-initiated atom transfer radical polymerization from a PSA-conjugated sensor chip with a functional monomer-bearing carboxy and secondary amine groups as interaction and post-imprinting modification (PIM) sites, respectively. PSA was orientationally conjugated on the sensor chip through diesters between the immobilized 3-fluorophenyl boronic acid and the cis-diol groups of PSA glucans. Treatment with the capping agent selectively inactivated low-affinity recognition cavities while protecting high-affinity cavities with the addition of a low concentration of PSA as a dynamic protection agent. The MIP thickness is critical in the present molecular imprinting, as a value of less than 5 nm can enable high selectivity. We believe that the proposed strategy based on a non-covalent molecular imprinting approach combined with a PIM-based capping treatment provides a novel method for the development of highly sensitive and selective glycoprotein recognition materials for use in biomarker sensing.

Keywords: 208 Sensors and actuators; 30 Bio-inspired and biomedical materials; Molecular imprinting; biomarker sensing; post-imprinting modifications.

Grants and funding

This work was partially supported by Japan Society for the Promotion of Science, JSPS KAKENHI Grant Numbers JP15K14943, JP16K18300, JP18K14252 and JP18H05398, and Japan Science and Technology Agency, the Matching Planner Program MP27115663368 and MP28116808085. This work was also partially supported by the Cooperative Research Program of ‘Network Joint Research Center for Materials and Devices’.