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

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.

A stable biocompatible porous coordination cage promotes in vivo liver tumor inhibition

“…S1-S7 in the ESM. The cage complex PCC-1 was designed and synthesized by solvothermal method by our group [26]. It was obtained as bright yellow polyhedron shaped crystals from the N,N-dimethylformamide (DMF) solution.…”

“…Previously, we successfully applied three kinds of PCCs for targeting designated subcellular organelles within the living cells. It was found that specific targeting delivery of anti-cancer drug will significantly improve cytotoxicity for different cell lines [26].…”

Guest‐Induced Transformations in Metal‐Organic Cages

“…Host-guest chemistry is a key feature of MOCs that has been extensively studied. [21][22][23][24][25] The incorporation of chemicals within the well-enclosed cage interior promotes the stabilization, [26,27] protection, [28][29] and new reactivity of guest molecules, [21,30] these effects have found use in molecular recognition, [31][32][33] chemical sensing, [34][35][36][37] gas capture, [38][39][40][41][42][43] molecular separations, [44][45][46] drug delivery, [47][48][49][50][51] bioimaging [21,52,53] as well as the exploration of new catalysis pathways. [21,22,[54][55][56][57][58][59][60] All binding events also cause subtle structural host perturbations, with negligible effects in most cases.…”

Controlled hierarchical self-assembly of networked coordination nanocapsulesviathe use of molecular chaperones

“…2,3 Metallosupramolecular assemblies such as metal-organic nanocapsules (MONCs) and/or nanocages are potentially useful models for such complex biological processes, 4,5 and are also promising with regard to energy storage, [6][7][8][9][10] molecular encapsulation, [11][12][13][14][15] catalytic, [16][17][18] and biomedical applications. 19,20 To date, synthetic chemists have been able to isolate discrete cages consisting of more than 100 precisely designed units through metal coordination. 21 A longstanding challenge, however, is the rational combination of simple components to form hierarchical superstructures with a similar level of assembly complexity as proteins.…”