Unexpected Photocatalytic Degeneration of NAD^(+) for Inducing Apoptosis of Hypoxia Cancer Cells

Developing customized chemical reactions that could regulate a specific biological process on demand is regarded as an advanced and promising strategy for treating diseases.However,conventional chemical reactions become challenging in complex physiological environments,which demand mild reaction conditions,high efficiency,good biocompatibility,and strong controllability.Moreover,the effects of the achieved reactions on the real biological system are usually further lessened.Herein,we describe an advanced photocatalytic reaction that irreversibly converted nicotinamide adenine dinucleotide(NAD+)to nicotinamide and adenosine diphosphate(ADP)-ribose by the cationic conjugated poly(fluorene-co-phenylene)(PFP).This reaction was introduced to tumor cells and triggered cell apoptosis.Under white-light illumination,the photocatalytic reaction decreased the NAD+ratio in tumor cells,disrupted the mitochondrial membrane potential,inhibited the synthesis of adenosine triphosphate(ATP),and effectively induced apoptosis.We propose a mechanism of the reaction where PFP is photoexcited to PFP*,and the obtained photoelectrons are transferred from PFP*to NAD+to produce nicotinamide and another unstable intermediate,ADP-ribosyl radical.ADP-ribosyl radical quickly reacts with triethanolamine to form ADP-ribose.This intracellular utilization of a specific photocatalytic reaction could offer a new approach to affect biological function for efficient cancer treatment.

Synthesis of easily-processable collagen bio-inks using ionic liquid for 3D bioprinted liver tissue models with branched vascular networks

Bioprinting has been a flouring way to fabricate complex tissue and organ mimics via precisely depositing printable cell-laden biomaterials.However,there is a limited number of biomaterials that fulfill the mechanical property of printing while meeting the responsive environment desired for the cells.Despite excellent cell compatibility and bioactivity,collagen suffers from difficulties in processing and printability which inhibited its utilization in three-dimensional(3D)bioprinting.Herein,we address this limitation by using ionic liquid as the solvent in the modification process,enabling collagens modified with quantified norbornene for chemical crosslink and extrusion-based 3D printing.With improved solubility and rheological properties,norbornene-functionalized collagen(Col-Nor)exhibited better shape fidelity in extrusion-based 3D printing compared with the one before modification.Photo-crosslinked Col-Nor hydrogel provided structural support and promoted the adhesion,proliferation,and differentiation of various types of cells,which afforded a centimeter-scale liver tissue model.This highly generalizable methodology expands printable,versatile,and tunable hydrogels developed from the natural extracellular matrix,allowing the biofabrication of 3D liver tissue model with branched vascular networks.

Solar-Driven Producing of Value-Added Chemicals with Organic Semiconductor-Bacteria Biohybrid System

Photosynthetic biohybrid systems exhibit promising performance in biosynthesis;however,these systems can only produce a single metabolite and cannot further transform carbon sources into highly valuable chemical production.Herein,a photosynthetic biohybrid system integrating biological and chemical cascade synthesis was developed for solar-driven conversion of glucose to value-added chemicals.A new ternary cooperative biohybrid system,namely bacterial factory,was constructed by self-assembling of enzyme-modified light-harvesting donor-acceptor conjugated polymer nanoparticles(D-A CPNs)and genetically engineered Escherichia coli(E.coli).The D-A CPNs coating on E.coli could effectively generate electrons under light irradiation,which were transferred into E.coli to promote the 37%increment of threonine production by increasing the ratio of nicotinamide adenine dinucleotide phosphate(NADPH).Subsequently,the metabolized threonine was catalyzed by threonine deaminase covalently linking with D-A CPNs to obtain 2-oxobutyrate,which is an important precursor of drugs and chemicals.The 2-oxobutyrate yield under light irradiation is increased by 58%in comparison to that in dark.This work provides a new organic semiconductor-microorganism photosynthetic biohybrid system for biological and chemical cascade synthesis of highly valuable chemicals by taking advantage of renewable carbon sources and solar energy.

天然来源的纳米类囊体应用于肿瘤的多模式治疗

多模式联合治疗已成为抗肿瘤的有效手段,但目前已报道的多模式肿瘤治疗试剂通常需要复杂的功能组分和繁琐的合成过程.因此,开发一种简单制备的天然来源多模式肿瘤治疗试剂仍然是一个挑战.本文从菠菜叶片中提取出了一种天然来源的、具有类酶性质的纳米类囊体用于肿瘤的多模式治疗.结果表明,纳米类囊体具有良好的光热转换和光敏化性质,可以有效杀伤4T1和MCF-7肿瘤细胞.同时,该材料还具有类过氧化物酶的性质,可以氧化分解过氧化氢产生羟基自由基从而诱导肿瘤细胞凋亡.因MCF-7肿瘤细胞内过量表达过氧化氢,该材料可实现对MCF-7肿瘤细胞的选择性杀伤.该纳米类囊体在细胞水平和活体小动物水平对肿瘤具有显著的治疗效果,且表现出良好的生物安全性.研究表明,该纳米类囊体具有光热转换、光敏化、类过氧化物酶的性质,是一类很有应用前景的多模式肿瘤治疗试剂.