Molecularly Imprinted Nanogels Acquire Stealth In Situ by Cloaking Themselves with Native Dysopsonic Proteins

• Published in: Angewandte Chemie International Edition 2017-06, Vol.56 (25), p.7088-7092
• Main Authors: Takeuchi, Toshifumi, Kitayama, Yukiya, Sasao, Reo, Yamada, Takuya, Toh, Kazuko, Matsumoto, Yu, Kataoka, Kazunori
• Format: Article
• Language: English
• Subjects: Albumin; Animals; Bioaccumulation; Blood circulation; Cancer; Chromatography, Gel; Drug Carriers; drug delivery; Energy transfer; Fluorescein; Fluorescence; Fluorescence Resonance Energy Transfer; Gels - chemistry; HeLa Cells; Humans; Intravenous administration; Liver; Mice; Molecular Imprinting; molecular recognition; Nanoparticles - chemistry; Nanostructure; NIH 3T3 Cells; Opsonin Proteins - chemistry; polymer nanogels; Protein Corona - chemistry; protein coronas; Proteins; Rhodamine; Serum Albumin, Human - chemistry; Serum Albumin, Human - isolation & purification; Stealth technology; Surface Plasmon Resonance
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201700647

Protein corona formation was regulated on the surface in vivo by molecular imprinting to enable polymeric nanogels to acquire stealth upon intravenous administration. Albumin, the most abundant protein in blood, was selected as a distinct protein component of protein corona for preparing molecularly imprinted nanogels (MIP‐NGs) to form an albumin‐rich protein corona. Intravital fluorescence resonance energy transfer imaging of rhodamine‐labeled albumin and fluorescein‐conjugated MIP‐NGs showed that albumin was captured by MIP‐NGs immediately after injection, forming an albumin‐rich protein corona. MIP‐NGs circulated in the blood longer than those of non‐albumin‐imprinted nanogels, with almost no retention in liver tissue. MIP‐NGs also passively accumulated in tumor tissue. These data suggest that this strategy, based on regulation of the protein corona in vivo, may significantly influence the development of drug nanocarriers for cancer therapy. But can they fire while cloaked? Molecular imprinting was used to cloak polymeric nanogels (MIP‐NGs) with a human serum albumin‐rich protein corona for use as a nanocarrier, resulting in longer circulation times in the blood and almost no retention in liver tissue. MIP‐NGs also passively accumulated in tumor tissue. The stealth properties were acquired in situ without the need to pretreat with albumin, minimizing toxic side effects.