Sonodynamic therapy (SDT) is noninvasive and possesses high bodypenetration depth, showing great potential for the treatment of deep-seated solid tumors. The efficacy of SDT, however, is limited by widespread hypoxia in solid tumors. Given this, an ultrasound-activated nanosystem is developed by integrating ferrate(VI) and protoporphyrin IX into biodegradable hollow mesoporous organosilica nanoplatforms, followed by assembling a phasechange material of lauric acid. The ferrate(VI) effectively reacts with water as well as overexpressed hydrogen peroxide and glutathione (GSH) in tumor cells, leading to tumor-microenvironment-independent oxygen production and in situ GSH depletion in tumors. More importantly, significant reactive oxygen species (ROS) overproduction is simultaneously achieved by protoporphyrin-augmented SDT and intracellular Fenton chemistry. Furthermore, the mild hyperthermia induced by ultrasound can trigger the phase change of lauric acid, achieving ultrasound-responsive control over the release of oxygen and ROS, and the depletion of GSH. The simultaneous oxygen generation, in situ GSH depletion, and ROS overproduction play a synergetic role in sensitizing SDT toward hypoxic solid tumors, which is verified by the remarkable improvement of hypoxic environments and more significant growth inhibition of SDT against osteosarcoma both in vitro and in vivo, showing promising application in hypoxic solid tumor treatment.

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We describe a fully stereodivergent synthesis of a range of α,α-disubstituted α-amino acids via an Ir/Cu-catalyzed α-allylation of readily available imine esters. The introduction of a Cu-Phox complex-activated imine ester into the chiral iridium-catalyzed allylic allylation process is crucial for its high reactivity and excellent enantio- and diastereoselectivity (up to>99% ee and >20:1 dr). Importantly, the two chiral catalysts allow for full control over the configuration of the stereocenters, affording all stereoisomers of the desired products. The utility of this methodology was demonstrated by synthesizing dipeptides and analogues of bioactive molecules in a stereodivergent manner.

We report a stereoselective and site-specific allylic alkylation of Schiff base activated amino acids and small peptides via a Pd/Cu dual catalysis. A range of noncoded α,α-dialkyl α-amino acids were easily synthesized in high yields and with excellent enantioselectivities (up to >99% ee). Furthermore, a direct and highly stereoselective synthesis of small peptides with enantiopure α-alkyl or α,α-dialkyl α-amino acids residues incorporated at specific sites was accomplished using this dual catalyst system.