posted on 2023-12-09, 14:07authored byZhifeng Xiao, Hengyu Lin, Hannah F. Drake, Joshua Diaz, Hong-Cai Zhou, Jean-Philippe Pellois
The
porous coordination cage PCC-1 represents a new platform potentially
useful for the cellular delivery of drugs with poor cell permeability
and solubility. PCC-1 is a metal–organic polyhedron constructed
from zinc metal ions and organic ligands through coordination bonds.
PCC-1 possesses an internal cavity that is suitable for drug encapsulation.
To better understand the biocompatibility of PCC-1 with human cells,
the cell entry mechanism, disassembly, and toxicity of the nanocage
were investigated. PCC-1 localizes in the nuclei and cytoplasm within
minutes upon incubation with cells, independent of endocytosis and
cargo, suggesting direct plasma membrane translocation of the nanocage
carrying its guest in its internal cavity. Furthermore, the rates
of cell entry correlate to extracellular concentrations, indicating
that PCC-1 is likely diffusing passively through the membrane despite
its relatively large size. Once inside cells, PCC-1 disintegrates
into zinc metal ions and ligands over a period of several hours, each
component being cleared from cells within 1 day. PCC-1 is relatively
safe for cells at low micromolar concentrations but becomes inhibitory
to cell proliferation and toxic above a concentration or incubation
time threshold. However, cells surviving these conditions can return
to homeostasis 3–5 days after exposure. Overall, these findings
demonstrate that PCC-1 enters live cells by crossing biological membranes
spontaneously. This should prove useful to deliver drugs that lack
this capacity on their own, provided that the dosage and exposure
time are controlled to avoid toxicity.