Serious side effects from
chemotherapies are the main problem with
cancer treatments. To solve these issues, precision
cancer nanomedicine based on natural therapeutic materials is developed, which enables specifically apoptosis by interacting with genetic mutation in
cancer cells, while leaving normal cells unaffected. Here, we report a novel nanomedicine (CuQDA/IO@HA) composed of
hyaluronic acid (HA) /
copper ion (Cu(II))-chelated
dextran-
aldehyde (DA)-
quercetin (Q) with dual targeting for synthetic lethal
therapy. The CuQDA/IO@HA prepared using a ratio of
metal/Q at 0.5:1 resulted in a stable particle structure with uniform particle distribution. The CuQDA/IO@HA can specifically target and induce specific cytotoxicity in BRCA-mutant
cancer cells in vitro. Combination treatment with CuQDA/IO@HA and magnetic navigation can induce
poly (ADP-ribose) polymerase (PARP) inhibition and DNA damage in BRCA-mutant
triple-negative breast cancer (TNBC) via CD44 targeting. The dual-targeting CuQDA/IO@HA can extend the median survival of the BRCA-mutant xenograft mice from 34 to 61 days in comparison to Q treatment alone in vivo, which is attributed to the significant increase in γH2AX, leading to significant apoptosis. More importantly, the CuQDA/IO@HA displayed biocompatibility and no obvious side-effect in normal organs. These results demonstrate the promising potential of integrating natural and
metal ions into a nanomedicine that can provide
precision medicine through synthetic lethality.