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 using in cancer nanotherapy and to elucidate fundamental insight regarding subcellular compartment targeting. Herein we show that the transportation of PCC cargo vectors though various subcellular barriers of mammalian cell can be manipulated by tuning the vector’s electronic property and surface affinity. It was found that the PCCs became selectively aggregated at the cell membrane, the cytoplasm, or the nucleus, respectively. When a DNA topoisomerase inhibitor was delivered into the nucleus by a neutral and lipophilic PCC, the anti-cancer efficacy was dramatically improved. Our 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. Our research also offers key insight into the engineering of nanoscopic materials for the furnishing cell organelle-specificity purpose.

Subcellular compartment targeting manipulated by porous coordination cages for cancer nanotherapy

2019 Spring National Meeting

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