The invention discloses a dual-miRNA-initiated
master key-
drug delivery system and a construction method and application thereof. The dual-miRNA-initiated
master key-
drug delivery system comprises a gold nanocage, a fluorescent
chemotherapy drug and
a DNA bridge-type nanolock, wherein the fluorescent
chemotherapy drug is loaded in a hole cavity of the gold nanocage, the
DNA bridge-type nanolock is combined with the surface of the gold nanocage to block the hole cavity of the gold nanocage, the
DNA bridge-type nanolock is composed of SH-modified long-chain
DNA S1, SH-modified long-chain DNA S2, long-chain DNA S3 with a composition sequence of an Mg <2+>
enzyme structure and long-chain DNA S4 with an Mg<2+>
enzyme recognition sequence, the S1 and the S2 are combined with the surface of the gold nanocage through gold-
sulfur bonds, the S3 and the S1 are in partial-base-complementary connection, and the two ends of the S4 are respectively in base-complementary connection with free ends of the S1 and the S2. The function of unlocking a plurality of locks can be executed by a
master key by utilizing a
cell endogenous substance Mg<2+>-dependent DNA
enzyme cyclic shearing reaction, and a drug is released in
cancer cells in a targeted and enhanced manner, so that the
signal-amplification diagnosis and treatment function of a probe is realized.