LncFASA promotes cancer ferroptosis via modulating PRDX1 phase separation

Ferroptosis, a unique type of non-apoptotic cell death resulting from iron-dependent lipid peroxidation, has a potential physiological function in tumor suppression, but its underlying mechanisms have not been fully elucidated. Here, we report that the long non-coding RNA(lncRNA) LncFASA increases the susceptibility of triple-negative breast cancer(TNBC) to ferroptosis. As a tumor suppressor, LncFASA drives the formation of droplets containing peroxiredoxin1(PRDX1), a member of the peroxidase family, resulting in the accumulation of lipid peroxidation via the SLC7A11-GPX4 axis. Mechanistically, LncFASA directly binds to the Ahpc-TSA domain of PRDX1, inhibiting its peroxidase activity by driving liquid-liquid phase separation, which disrupts intracellular ROS homeostasis. Notably, high LncFASA expression indicates favorable overall survival in individuals with breast cancer, and LncFASA impairs the growth of breast xenograft tumors by modulating ferroptosis. Together, our findings illustrate the crucial role of this lncRNA in ferroptosis-mediated cancer development and provide new insights into therapeutic strategies for breast cancer.

A synergetic strategy of NIR-Ⅱ squaraine dyes with ultrahigh photothermal conversion efficiency for photothermal therapy

Recent research on photothermal therapy(PTT) has sparked significant interest in the development of new organic photothermal agents(PTAs),ranging from single-molecule to aggregated levels.However,controlling aggregation pathways for PTAs with ultrahigh photothermal conversion efficiency(PCE) remains a major challenge.Herein,a two-pronged approach utilizing “Haggregation” and “intramolecular motion” was employed to enhance the PCE of an acceptor-substituted squaraine dye(NSQs).The C2vmolecular symmetry of the NSQs,which possess a ground state dipole moment(μg),promotes H-dimeric aggregates through dipole-dipole counteraction.Peripheral triphenylethylene or diphenylamine groups were added to this H-dimeric nanoplatform.This was done to enhance intramolecular motions for heat generation and also to extend conjugation,which redshifted the optical absorption and balanced the blue-shift induced by H-aggregation.With this technique,an organic PTA with NIR-II absorption was developed,and its nanoparticle achieved a remarkable PCE of 86.3% under 1,064 nm laser excitation.Femtosecond transient absorption spectroscopy and quantum mechanical calculations demonstrated the accelerated internal conversion process in NIR-II PTAs for rapid heat generation.The NSQs nanoparticles exhibit superior photothermal therapeutic properties for in vivo photoacoustic imaging-guided PTT,demonstrating the potential of bottom-up design to enable synergistic engineering strategies towards efficient phototheranostic agents.