Light amplified oxidative stress in tumor microenvironment by carbonized hemin nanoparticles for boosting photodynamic anticancer therapy

Photodynamic therapy(PDT),which utilizes light excite photosensitizers(PSs)to generate reactive oxygen species(ROS)and consequently ablate cancer cells or diseased tissue,has attracted a great deal of attention in the last decades due to its unique advantages.However,the advancement of PDT is restricted by the inherent characteristics of PS and tumor microenvironment(TME).It is urgent to explore high-performance PSs with TME regulation capability and subsequently improve the therapeutic outcomes.Herein,we reported a newly engineered PS of polymer encapsulated carbonized hemin nanoparticles(P-CHNPs)via a facile synthesis procedure for boosting photodynamic anticancer therapy.Solvothermal treatment of hemin enabled the synthesized P-CHNPs to enhance oxidative stress in TME,which could be further amplified under light irradiation.Excellent in vitro and in vivo PDT effects were achieved due to the improved ROS(hydroxyl radicals and singlet oxygen)generation efficiency,hypoxia relief,and glutathione depletion.Moreover,the superior in vitro and in vivo biocompatibility and boosted PDT effect make the P-CHNPs a potential therapeutic agent for future translational research.

prpf4 is essential for cell survival and posterior lateral line primordium migration in zebrafish

Prpf4(pre-mRNA processing factor 4),a key component of spliceosome,plays critical roles in pre-mRNA splicing and its mutations result in retinitis pigmentosa due to photoreceptor defects.In this study,we characterized a zebrafishharboring a Tol2 transposon-based gene trap cassette in the third intron of the prpf4 gene.Cells in the brain and spinal cord gradually undergo p53-dependent apoptosis after 28 hpf insuggesting that a widespread function of prpf4 in neural cell survival.In addition,prpf4 is essential for survival of posterior lateral line primordial(pLLP)cells.prpf4 deficiency perturbs Fgf,and chemokine signaling pathways and impairs pLLP migration.RNA-Seq analysis suggests that prpf4 deficiency may impair spliceosome assembly,leading to compensatory upregulation of core spliceosomal genes and alteration of pre-mRNA splicing.Taken together,our studies uncover an essential role of prpf4 in pre-m RNA splicing,cell survival and pLLP migration.