The
purpose of developing novel anticancer drug delivery systems
(DDSs) is to efficiently carry and release drugs into cancer cells
and minimize side effects. In this work, based on hollow mesoporous
silica nanoparticle (HMSN) and the charge-reversal property, a pH/GSH-dual-sensitive
DDS named DOX@HMSN–SS-PLL(cit) was reported. HMSN encapsulated
DOX with high efficacy and was then covered by the “gatekeeper”
β-cyclodextrin (β-CD) through the glutathione (GSH)-sensitive
disulfide bond. Thereafter, adamantine-blocked citraconic-anhydride-functionalized
poly-l-lysine (PLL(cit)-Ad) was decorated on the surface
of the particles via host–guest interaction. The negatively
charged carriers were stable in the neutral environment in vivo and
could be effectively transported to the tumor site. The surface charge
of the nanoparticles could be reversed in the weakly acidic environment,
which increased the cellular uptake ability of the carriers by the
cancer cells. After cellular internalization, β-CD can be removed
by breakage of the disulfide bond in the presence of a high concentration
of GSH, leading to DOX release. The preparation process of the carriers
was monitored. The charge-reversal capability and the controlled drug-release
behavior of the carriers were also investigated. In vitro and in vivo
experiments demonstrated the excellent cancer therapy effect with
low side effects of the carriers. It is expected that dual-sensitive
DOX@HMSN–SS-PLL(cit) could play an important role in cancer
therapy.
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