To optimize synergistic cancer therapy, we rationally assemble an inorganic-organic nanocomplex using a folate-modified lipid bilayer spread on photosensitizer-entrapped mesoporous silica nanoparticle (MSN) coated gold nanorods (AuNRs). In this hybrid bioconjugate, the large specific surface area and pore size of AuNR@MSN guarantee a high loading capacity of small photosensitive molecules. The modification with selective mixed liposomes on the surface of AuNR@MSN enables faster cellular internalization and enhancement of endocytosis. Under one-time NIR two-photon illumination, AuNR-mediated hyperthermia can kill cancer cells directly. Meanwhile, the loaded photosensitizer, hypocrellin B, generates two kinds of reactive oxygen species (ROS) to induce cell apoptosis. Remarkably, hyperthermia can improve the yield of ROS. After intravenous injection of this bioconjugate into female BALB/c nude mice followed by laser irradiation (808 nm, 1.3 W cm(-2), 6 min), the tumor growth is suppressed completely. The tumors are not recurrent within the observation time (19 days), and the normal or main organs are not obviously pathological. Thus, such a simplified and selective cancer treatment, combining photothermal and photodynamic therapy in a synergistic manner, provides outstanding efficiency in vivo. This nanocomplex with well-defined core@shell nanostructures integrated with a two-photon technique holds great promise to improve cancer phototherapy with a high efficiency in the clinic.
The construction of quickly dissociating containers holding bioactive components that meet the extreme requirements of emergency treatment is highly desirable but remains a great challenge. Here the use of small-molecule-induced dynamic covalent assembly is reported for simple and tunable fabrication of a biocompatible diphenylalanine-based nanocontainer toward rapidly responsive cargo delivery. The assembled nanocontainer can adaptively encapsulate various charged or neutral molecules. Upon biofluid trigger, the encapsulated molecules and bioactive proteins are released in a burst (within 5 s) from the nanocontainer due to highly sensitive deprotonation-mediated disruption of hydrogen bonding. This highlighted feature allows the nanocontainer as an excellent "fast dissolving" delivery vehicle available in spray dosage form for medical emergencies, as demonstrated by in vivo application for massive hemorrhage.
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