Stimuli-responsive nanoparticles with multiple therapeutic/diagnostic functions are highly desirable for effective tumor treatment. Herein novel caspase-3 responsive functionalized upconversion nanoparticles (CFUNs) were fabricated with three-in-one functional integration: near-infrared (NIR) triggered photodynamic damage along with caspase-3 activation, subsequent caspase-3 responsive drug release, and cascade chemotherapeutic activation. CFUNs were formulated from the self-assembly of caspase-3 responsive doxorubicin (DOX) prodrug tethered with DEVD peptide (DEVD-DOX), upconversion nanoparticles (UCNP), a photosensitizer (pyropheophorbide-a methyl ester, MPPa), and tumor-targeting cRGD-PEG-DSPE to afford multifunctional CFUNs, MPPa/UCNP-DEVD-DOX/cRGD. Upon cellular uptake and NIR irradiation, the visible light emission of UCNP could excite MPPa to produce reactive oxygen species for photodynamic therapy (PDT) along with the activation of caspase-3, which further cleaved DEVD peptide to release DOX within tumor cells, thus accomplishing NIR-triggered PDT and cascade chemotherapy. CFUNs presented silent therapeutic potency and negligible cytotoxicity in the dark, whereas in vitro and in vivo experiments demonstrated the NIR-triggered cascade therapeutic activation and tumor inhibition due to consecutive PDT and chemotherapy. Current NIR-activated cascade tumor therapy with two distinct mechanisms is significantly favorable to overcome multidrug resistance and tumor heterogeneity for persistent tumor treatment.
We demonstrated a novel nanocomposite based on fluorescent turn-on gold nanostars for simultaneous tumor targeting photothermal therapy (PTT) and feedback apoptosis imaging of the self-therapeutic effect. In this theranostic agent ( [email protected] ), gold nanostars (AuNSs) and fluorescent dye Atto 655, as a fluorophore/quencher pair, were conjugated to form intermolecular fluorescence quenching in virtue of the linkage of a caspase-3 responsive peptide. Folic acid targeting moiety facilitated the selective accumulation in cancer cells via receptor-mediated endocytosis. Upon photo irradiation, [email protected] demonstrated excellent photothermal effect and induced cell death with apoptosis related mechanism. The typical apoptosis-effector proteases, caspase-3, was subsequently activated and terminated intramolecular fluorescent quenching process. Obvious fluorescence recovery could be applied to precisely assess the activated caspase-3 expression and the real time therapeutic efficacy. This novel versatile nanocomposite could serve as a theranostic agent for tumor targeting PTT and also provide self-therapeutic monitoring for precise cancer therapeutic applications.
危险品化学品经营许可证（带存储）