In vivo stealthified molecularly imprinted polymer nanogels incorporated with gold nanoparticles for radiation therapy.

Radiation therapy is a representative therapeutic approach for cancer treatment, wherein the development of efficient radiation sensitizers with low side effects is critical. In this study, a novel stealth radiation sensitizer based on Au-embedded molecularly imprinted polymer nanogels (Au MIP-NGs) was developed for low-dose X-ray radiation therapy. Surface plasmon resonance measurements reveal the good affinity and selectivity of the obtained Au MIP-NGs toward the target dysopsonic protein, human serum albumin. The protein recognition capability of the nanogels led to the formation of the albumin-rich protein corona in the plasma. The Au MIP-NGs acquire stealth capability in vivo through protein corona regulation using the intrinsic dysopsonic proteins. The injection of Au MIP-NGs improved the efficiency of the radiation therapy in mouse models of pancreatic cancer. The growth of the pancreatic tumor was inhibited even at low X-ray doses (2 Gy). The novel strategy reported in this study for the synthesis of stealth nanomaterials based on nanomaterial-protein interaction control shows significant potential for application even in other approaches for cancer treatment, diagnostics, and theranostics. This strategy paves a way for the development of a wide range of effective nanomedicines for cancer therapy.

Molecularly Imprinted Nanogels Possessing Dansylamide Interaction Sites for Controlling Protein Corona In Situ by Cloaking Intrinsic Human Serum Albumin.

Nanomaterials have become increasingly promising for biomedical applications owing to their specific biological characteristics. As drug delivery vehicles, nanomaterials have to circulate in the bloodstream to deliver the encapsulated components to the target tissues. Protein corona regulation is one of the promising approaches that gives stealth capability to avoid immune response. The aim of this study was to develop molecularly imprinted polymer nanogels (MIP-NGs) capable of protein corona regulation, using intrinsic human serum albumin (HSA) and with a functional monomer, dansylamide ethyl acrylamide (DAEAm), the dansylamide group serving as a ligand for HSA. The recognition capability of HSA for MIP-NGs was investigated by isothermal titration calorimetry (ITC). The affinity of the MIP-NGs prepared with DAEAm was then compared to that of the reference MIP-NGs prepared with pyrrolidyl acrylate developed in our previous study. Furthermore, we demonstrated that the concurrent use of these two different functional monomers for molecular imprinting was further effective to construct high-affinity recognition nanocavities for HSA and to form HSA-rich protein corona in the human plasma owing to the different interaction modes of the monomers. We believe that the molecular imprinting strategy developed through the use of ligand-based functional monomer is an effective strategy to create artificial molecular recognition materials.

Gold Nanoparticle-Incorporated Molecularly Imprinted Microgels as Radiation Sensitizers in Pancreatic Cancer.

Radiation therapy is a powerful approach for treating pancreatic cancer, a representative refractory cancer with a high fatality rate, and efforts have been made to decrease the radiation dose and suppress the side effects related to damage to normal tissues during radiation therapy. Gold nanoparticles (Au NPs) are known to possess radiosensitizing activity and low biotoxicity; however, Au NP-incorporated biomaterials have not been investigated as feasible radiosensitizers for use in vivo. Accordingly, in this study, Au NP-incorporated molecularly imprinted polymer microgels (Au-MIP microgels) were created as radiation sensitizers using a newly developed one-pot seeded precipitation polymerization method, and the radiation-sensitizing effects of the Au-MIP microgels were investigated in mice bearing pancreatic tumors. In mice injected with the Au-MIP microgels, tumor sizes were smaller than those in control mice injected with buffer solution when X-ray irradiation was performed. Furthermore, biotoxicity was not observed in mice injected with the Au-MIP microgels because of negligible body weight loss in these mice. Based on these findings, Au-MIP microgels may have applications as novel radiation sensitizers in radiation therapy.