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Small. 2018 Nov;14(47):e1802709. doi: 10.1002/smll.201802709. Epub 2018 Sep 17.

Investigating Subcellular Compartment Targeting Effect of Porous Coordination Cages for Enhancing Cancer Nanotherapy.

Author information

1
Department of Chemistry, Texas A&M University, College Station, TX, 77843, USA.
2
Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
3
Department of Biology, Texas A&M University, College Station, TX, 77843, USA.
4
Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX, 77843, USA.

Abstract

Understanding the key factors for successful subcellular compartment targeting for cargo delivery systems is of great interest in a variety of fields such as bionanotechnology, cell biology, and nanotherapies. However, the fundamental basis for intracellular transportation with these systems has thus far rarely been discussed. As a cargo vector, porous coordination cages (PCCs) have great potential for use in cancer nanotherapy and to elucidate fundamental insight regarding subcellular compartment targeting. Herein, it is shown that the transportation of PCC cargo vectors though various subcellular barriers of the mammalian cell can be manipulated by tuning the vector's electronic property and surface affinity. It is found that the PCCs become selectively aggregated at the cell membrane, the cytoplasm, or the nucleus, respectively. When a DNA topoisomerase inhibitor is delivered into the nucleus by a neutral and lipophilic PCC, the anticancer efficacy is dramatically improved. The findings shed light to tune the interactions at the "bio-nano" interface. This study provides a key strategy for future work in targeting specific cell organelles for cell imaging, cargo delivery, and therapy. This research also offers key insight into the engineering of nanoscopic materials for furnishing cell organelle-specificity.

KEYWORDS:

cancer therapy; cell compartment targeting; coordination cage; cytotoxicity; subcellular distribution

PMID:
30222252
PMCID:
PMC6563816
[Available on 2019-11-01]
DOI:
10.1002/smll.201802709

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