Integrating multimodality
bioimaging and multiple stimuli-responsive
controlled drug release properties into one single nanosystem for
therapeutic application is highly desirable but still remains a challenge.
Herein, we coated a hollow mesoporous silica shell on to upconversion
nanoparticles (UCNPs) and conjugated pillarene-based supramolecular
valves on to surface of UCNPs@hm-SiO2 using amine-coumarin
phototriggers to obtain the multifunctional nanoparticles, UCNPs@hm-SiO2-Cou-Cys-DOX/WP[5]. Benefiting from the core–shell
structured UCNPs, the UCNPs@hm-SiO2-Cou-Cys-DOX/WP[5] can
serve as efficient contrast agents for upconversion luminescence and T
1-weighted magnetic resonance imaging in vitro/in
vivo. More importantly, depending on exquisitely designed supramolecular
valves, UCNPs@hm-SiO2-Cou-Cys-DOX/WP[5] can realize zero-premature
release under normal physiological conditions (pH 7.4), which produces
minimal damage to normal tissue, whereas this nanosystem can respond
to several disease-related signals, including acid (most cancers),
alkali (metabolic alkalosis), and Zn2+ (Alzheimer’s
disease), along with two external stimuli, including near-infrared
(NIR) light and reductive electrical potential, via altering the spatial
structure of pseudorotaxanes, disassembling the molecular stalks,
or undergoing photochemical reactions, ultimately resulting in opening
of the gatekeepers and release of encapsulated drugs. The multifunctional
UCNP-based nanoparticles were endowed with such quintuple stimuli-responsive
controlled release characteristics. Specifically, in anticancer application,
the rational utilization of the two of them, acid and NIR light, could
regulate the release amount and rate of DOX from UCNPs@hm-SiO2-Cou-Cys-DOX/WP[5], accelerate the accumulation of DOX in
cell nuclei, and thereby promote the cancer cell apoptosis, indicating
that the nanomaterials have promising application in cancer treatment.
This study provides a novel design strategy for constructing multifunctional
UCNP-based nanoparticles with multiple stimuli-responsive drug release
features, which have great potential in diagnosis and therapy of relevant
diseases as theranostic nanomedicines.