Design and Application of Rolling Circle Amplification for a Tumor-Specific Drug Carrier

It
is challenging to design rolling circle amplification (RCA) for tumor-selective
delivery of drugs. Here, we devise a doxorubicin nanocarrier composed
of RCA products, cholesterol-DNA, and folate-DNA conjugates. RCA products,
designed to contain tandem repeats of short hairpin DNA, employ the
repeated sequences complementary to both DNA conjugates, and thus
RCA products/cholesterol-DNA/folate-DNA complexes, generated via sequential
base pairing processes, acquire the amphiphilic properties that facilitate
self-assembly into the highly condensed nanoparticles (RCA nanoparticles).
Doxorubicin-loaded RCA nanoparticles, especially with high cargo capacity,
release drugs to the environment with the aid of acidity and show
selective cytotoxicity to cancer cells. Particularly, the condensed
structures enable RCA nanoparticles to be resistant to nucleases in
the blood. These results show that RCA nanoparticles have great potential
as a doxorubicin carrier for targeted cancer therapy, and furthermore,
our strategy provides an alternative tool to exploit RCA techniques
on drug delivery systems.