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

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Title
Deep Tumor Penetration of Drug-Loaded Nanoparticles by Click Reaction-Assisted Immune Cell Targeting Strategy
Author(s)
Soo Hong Lee; Ok Kyu Park; Jonghoon Kim; Kwangsoo Shin; Pack C.G.; Kang Kim; Giho Ko; Lee N.; Kwon S.-H.; Taeghwan Hyeon
Publication Date
2019-09
Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, v.141, no.35, pp.13829 - 13840
Publisher
AMER CHEMICAL SOC
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. © 2019 American Chemical Society
URI
https://pr.ibs.re.kr/handle/8788114/6885
ISSN
0002-7863
Appears in Collections:
Center for Nanoparticle Research(나노입자 연구단) > Journal Papers (저널논문)
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