분자영상 및 방사화학

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  • [J Am Chem Soc.] Deep Tumor Penetration of Drug-Loaded Nanoparticles by Click Reaction-Assisted Immune Cell Targeting Strategy.종양의 혈관 깊숙한 곳에 약물 나노입자를 전달하기 위한 전략: click reaction-assisted immune cell targeting (CRAIT)

    국민대, KBSI, 서울대 / 이수홍, 이노현*, 권승혜*, 현택환*

  • 출처
    J Am Chem Soc.
  • 등재일
    2019 Sep 4
  • 저널이슈번호
    141(35):13829-13840. doi: 10.1021/jacs.9b04621. Epub 2019 Aug 22
  • 내용

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    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.

     


    Author information

    Lee SH1,2, Park OK1,2, Kim J1,2, Shin K1,2, Pack CG3, Kim K1,2, Ko G1,2, Lee N4, Kwon SH5, Hyeon T1,2.
    1
    Center for Nanoparticle Research , Institute for Basic Science (IBS) , Seoul 08826 , Republic of Korea.
    2
    School of Chemical and Biological Engineering, and Institute of Chemical Processes , Seoul National University , Seoul 08826 , Republic of Korea.
    3
    Asan Institute for Life Sciences, Asan Medical Center, Department of Convergence Medicine , University of Ulsan College of Medicine , Seoul 05505 , Republic of Korea.
    4
    School of Advanced Materials Engineering , Kookmin University , Seoul 02707 , Republic of Korea.
    5
    Division of Bio-imaging, Korea Basic Science Institute , Seoul 02841 , Republic of Korea.

  • 편집위원

    일반적으로 종양의 영상 및 치료를 위한 나노물질은 EPR (Enhanced Permeation and Retention) 효과를 통해 전달되는데, 물리적으로 종양 깊은 곳까지 전달되는 것은 한계가 있다. 이러한 한계를 극복하기 위해 이 연구에서는 click 반응을 이용하여 면역세포를 표적하는 CRAIT 법을 제시하고 있다. 이는 click 반응이 가능한 면역세포 표적 항체를 만들어서 먼저 유방암 동물에 주입한 후, 24 시간 뒤에 그 항체에 click 반응이 가능한 항암 나노입자(MSNs-Tz)를 추가 주사하여 종양 깊숙한 곳까지 나노입자가 들어가서 약물을 전달하는 결과를 보여주고 있다.

    2019-10-30 17:18:44

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