Nanoscale
coordination polymers are promising vehicles for anticancer
drug delivery because their surface composition and particle size
can be tuned to exploit the enhanced permeability and retention effect,
and their reversible interaction with metal cations enables triggered
drug release at the tumor site. Here, we develop a novel nanoscale
coordination polymer using the diblock copolymer poly(2-methacryloyloxyethyl
phosphorylcholine)-block-poly(serinyl acrylate) (PMPC-b-PserA) and demonstrate its use for encapsulation of a
hydrophobic drug and triggered drug release to induce breast cancer
cell apoptosis in vitro. The zwitterionic PMPC block
was inspired by the antifouling structure of cell membranes, and the
PserA block was inspired by the amphoteric amino acids of proteins.
The polymer was synthesized by reversible addition–fragmentation
chain transfer polymerization, and a mixture of the polymer and FeCl3 self-assembled into nanoparticles via complexation of Fe3+ with PserA, with the hydrophilic PMPC block at the particle
surface. At a molar ratio of Fe3+ to serA of 3:1, the hydrodynamic
diameter of the particles was 22.2 nm. Curcumin, a natural water-insoluble
polyphenol used to enhance the effects of chemotherapeutics, was encapsulated
in the particles as an oil-in-water emulsion, with an encapsulation
efficiency of 99.6% and a particle loading capacity of 32%. Triggered
release of curcumin was achieved by adding deferoxamine, an FDA-approved
Fe3+ chelating agent; curcumin release efficiency increased
at higher deferoxamine concentrations and lower pH. Triggered release
of curcumin induced apoptosis in human triple-negative breast cancer
cells; cell viability decreased to 34.3% after 24 h of treatment with
the curcumin-loaded nanoparticles and deferoxamine, versus >80%
viability
without deferoxamine to trigger drug release. The biocompatibility,
tunable composition and size, high hydrophobic drug loading, and triggered-release
capability of this nanoscale coordination polymer make it well-suited
for use in anticancer drug delivery.
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