한빛사 논문
Soo Hong Lee,†,‡ Ok Kyu Park,†,‡ Jonghoon Kim,†,‡ Kwangsoo Shin,†,‡ Chan Gi Pack,§ Kang Kim,†,‡ Giho Ko,†,‡ Nohyun Lee,*,∥ Seung-Hae Kwon,*,⊥ and Taeghwan Hyeon*,†,‡
† Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul 08826, Republic of Korea
‡ School of Chemical and Biological Engineering, and Institute of Chemical Processes, Seoul National University, Seoul 08826, Republic of Korea
§ Asan Institute for Life Sciences, Asan Medical Center, Department of Convergence Medicine, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea
∥ School of Advanced Materials Engineering, Kookmin University, Seoul 02707, Republic of Korea
⊥ Division of Bio-imaging, Korea Basic Science Institute, Seoul 02841, Republic of Korea
Author Contributions
S.H.L., O.K.P., and J.K., contributed equally to this work.
*Corresponding Authors : Nohyun Lee, Seung-Hae Kwon, Taeghwan Hyeon
Abstract
Nanoparticles have been extensively used to deliver therapeutic drugs to tumor tissues through the extravasation of a leaky vessel via enhanced permeation and retention effect (EPR, passive targeting) or targeted interaction of tumor-specific ligands (active targeting). However, the therapeutic efficacy of drug-loaded nanoparticles is hampered by its heterogeneous distribution owing to limited penetration in tumor tissue. Inspired by the fact that cancer cells can recruit inflammatory immune cells to support their survival, we developed a click reaction-assisted immune cell targeting (CRAIT) strategy to deliver drug-loaded nanoparticles deep into the avascular regions of the tumor. Immune cell-targeting CD11b antibodies are modified with trans-cyclooctene to enable bioorthogonal click chemistry with mesoporous silica nanoparticles functionalized with tetrazines (MSNs-Tz). Sequential injection of modified antibodies and MSNs-Tz at intervals of 24 h results in targeted conjugation of the nanoparticles onto CD11b+ myeloid cells, which serve as active vectors into tumor interiors. We show that the CRAIT strategy allows the deep tumor penetration of drug-loaded nanoparticles, resulting in enhanced therapeutic efficacy in an orthotopic 4T1 breast tumor model. The CRAIT strategy does not require ex vivo manipulation of cells and can be applied to various types of cells and nanovehicles.
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