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Deep Tumor Penetration of Drug-Loaded Nanoparticles by Click Reaction-Assisted Immune Cell Targeting Strategy

Cited 4 time in Web of Science Cited 4 time in Scopus
Authors
Lee, Soo Hong; Park, Ok Kyu; Kim, Jonghoon; Shin, Kwangsoo; Pack, Chan Gi; Kim, Kang; Ko, Giho; Lee, Nohyun; Kwon, Seung-Hae; Hyeon, Taeghwan
Issue Date
2019-09
Citation
Journal of the American Chemical Society, Vol.141 No.35, pp.13829-13840
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 nano particles 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 fiinctionalized 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.
ISSN
0002-7863
URI
http://hdl.handle.net/10371/165791
DOI
https://doi.org/10.1021/jacs.9b04621
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College of Engineering/Engineering Practice School (공과대학/대학원)Dept. of Chemical and Biological Engineering (화학생물공학부)Chemical Convergence for Energy and Environment (에너지환경 화학융합기술전공)Journal Papers (저널논문_에너지환경 화학융합기술전공)
College of Engineering/Engineering Practice School (공과대학/대학원)Dept. of Chemical and Biological Engineering (화학생물공학부)Journal Papers (저널논문_화학생물공학부)
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