In situ generation of anticancer agents at the place of the disease is a new paradigm for cancer therapy. The production of highly potent drugs by nanoreactors through a facile synthesis pathway is demanded. We report an oncolytic nanoreactor platform loaded with the enzyme glucose oxidase (GOX) to produce hydrogen peroxide. For the first time, we realized a core–shell structure with encapsulated GOX under mild synthetic conditions, which ensured high remaining activity of GOX inside of the nanoreactor. Moreover, the nanoreactor protected the loaded GOX from proteolysis and contributed to increased thermal stability of the enzyme. The nanoreactors were effectively taken up into different cancer cells, in which they produced hydrogen peroxide by consuming intracellular glucose and oxygen, thereby leading to effective death of the cancer cells. In summary, our robust nanoreactors are a promising platform for effective anticancer therapy and sustained enzyme utilization.

The regeneration of enzymatic cofactors by cell-free synthetic modulesi sak ey step towards producing ap urely synthetic cell. Herein, we demonstrate the regeneration of the enzyme cofactor NAD + by photo-oxidation of NADH under visible-light irradiation by using metal-free conjugated polymer nanoparticles. Encapsulation of the light-activen anoparticles in the lumen of polymeric vesicles produced af ully organic module able to regenerate NAD + in an enzyme-free system.T he polymer compartment conferred physical and chemicala utonomy to the module, allowing the regenerationo fN AD + to occur efficiently,e ven in harshc hemical environments. Moreover,w e show that regeneration of NAD + by the photocatalyst nanoparticles can oxidize am odel substrate, in conjunction with the enzymeg lycerol dehydrogenase. To ensure the longevity of the enzyme, we immobilizedi tw ithin ap rotectives ilica matrix;t his yieldede nzymatic silican anoparticles with enhanced long-term performance and compatibility with the NAD + -regeneration system.The immobilizationo re ncapsulationo ff unctional parts in artificial compartmentsi sapowerful way to create responsive autonomous objects, or functional modules, that displaylocalized input-output properties. [1] Synthetic biology uses artificially designed modules as systems that can reproduce simple cell-like activity and even mimic rudimentary cellular behavior. [2] Some examples include the cell-free synthesis of ATP, [3] cytoskeleton and microtubule reconstitution, [4] self-replication of giant vesicles, [5] and av ariety of compartmentalized biochemical reactions. [6] The cell-free regulation of nicotinamide adenine nucleotide (NAD) coenzymes has been an important target in photocatalysis and functional module design. [7] In cells, NAD coenzymes controlt he flow of electrons in numerous redox transformations involvingo xidoreductases and are key components for the conversion and storageo fe nergy during photosynthesis. Therefore, the ability to control the redox state of NAD in a functional module offers aw ay to simplify and optimize the use of numerous enzymatic redox transformations,m any of them with relevant synthetic applications. [8] Previous work in this area has focused mainly on creating NAD modules containing inorganic photocatalysts, such as TiO 2 and other metal-based nanoparticles, encapsulatedi nt he lumen of lipid vesicles or embedded in solid matrices. [9] To date, most developmentsi nt his area has focusedo nr egenerating NADH through the photocatalytic reduction of NAD + . These metal-based catalysts show high versatility,s electivity, and excellent photocatalytic properties, but they can also suffer from the need for mediators or excitation wavelengths in the UV region, whichc an be harmful to other components in the system.Herein, we report the designo fametal-free, polymer-based NAD module that regenerates NAD + through the nonenzymatic photocatalytic oxidation of NADH by using visiblel ight. Our photocatalyst consisted of conjugated microporous polymer nano...

Physical separation of reactions by interactive multicompartments in biological cells is an attractive motif to design efficient microreactors that create biomimetic cascade reactions. We present an aqueous compartment with three different subcompartments that comprise of silica nanoreactors with encapsulated enzymes, namely, β-glucosidase, glucose oxidase, and peroxidase, providing a model cascade reaction in confinement. The encapsulated enzymes retain their activity as the substrate can reach the active site and the silica shell further protects the enzymes from external stresses, such as heat and proteolytic degradation. We demonstrate the biomimetic cascade reaction in between the compartments ("organelles") inside of an additional microconfinement (water-in-oil emulsion). This strategy will allow us to design efficient multicompartmentalized reactors for further biological and organic reactions.

Circulating tumor cells (CTCs) have attracted considerable attention as promising markers for diagnosing and monitoring the cancer status. Despite many technological advances in isolating CTCs, the capture efficiency and purity still remain challenges that limit clinical practice. Here, the construction of "nanotentacle"-structured magnetic particles using M13-bacteriophage and their application for the efficient capturing of CTCs is demonstrated. The M13-bacteriophage to magnetic particles followed by modification with PEG is conjugated, and further tethered monoclonal antibodies against the epidermal receptor 2 (HER2). The use of nanotentacle-structured magnetic particles results in a high capture purity (>45%) and efficiency (>90%), even for a smaller number of cancer cells (≈25 cells) in whole blood. Furthermore, the cancer cells captured are shown to maintain a viability of greater than 84%. The approach can be effectively used for capturing CTCs with high efficiency and purity for the diagnosis and monitoring of cancer status.

Cationic magnetoliposomes enable to achieve efficient capture of cells and intracellular delivery of oligonucleotides into nucleus through cancer cell-specific targeting.