Coherent Control of the Photoionization of Pyrazine

Most attempts to control the absorption of resonant light by quantum mechanical interference have been limited to atoms and small molecules with specialized state configurations and selection rules. Here we illustrate experimentally the possibility of creating laser-induced transparencies in complex molecular systems. Our approach takes advantage of the nonadiabatic excited-state dynamics characteristic of polyatomic molecules. Specifically, we show that it is possible to construct femtosecond pulses using a genetic algorithm to suppress the ionization of isolated pyrazine molecules at a prespecified time. The data suggest that transparency is achieved by localization of a wave packet in a region of the coupled S₁/S₂ potential energy surfaces, where a vertical transition to the ionic state is energetically forbidden. This approach is general and does not require prior knowledge of the molecular Hamiltonian

Liposomal STAT3-Degrading PROTAC Prodrugs Promote Anti-Hepatocellular Carcinoma Immunity via Chemically Reprogramming Cancer Stem Cells

Cancer stem cells (CSCs) with hyperactivated signal transducer and activator of transcription 3 (STAT3) are a major driver of hepatocellular carcinoma (HCC). Herein, we report a nanointegrative proteolysis-targeting chimera (PROTAC)-based STAT3 degradation strategy that enables efficient chemical reprogramming of HCC-associated CSCs, which potently inhibits CSC growth while evoking anti-HCC immune responses. The PROTAC prodrug was synthesized by conjugating the STAT3 binding domain (inS3) with a thioketal-caged E3 ligase ligand (VL-TK) via an oligo(ethylene glycol) linker (OEG) with tuned length and flexibility and encapsulating it in cRGD-modified cationic liposomes for CSC-targeted delivery while facilitating their lysosomal escape. The PROTAC prodrugs were activated by the upregulated ROS levels in CSCs and efficiently degraded STAT3 for chemical reprogramming, which would not only impair their stemness features but also remodel the immunosuppressive TME into an immunosupportive state to boost anti-HCC immunity. This strategy provides an approach for improving HCC treatment in clinics