Conjugated Molecules Based Multi-Component Artificial Photosynthesis System for Producing Multi-Objective Products.

The development of artificial photosynthesis systems that mimics natural photosynthesis can help address the issue of energy scarcity by efficiently utilizing solar energy. Here, it presents liposomes-based artificial photosynthetic nanocapsules (PSNC) integrating photocatalytic, chemical catalytic, and biocatalytic systems through one-pot method. The PSNC contains 5,10,15,20-tetra(4-pyridyl) cobalt-porphyrin, tridipyridyl-ruthenium nitrate, oligo-pphenyl-ethylene-rhodium complex, and creatine kinase, efficiently generating oxygen, nicotinamide adenine dinucleotide (NADH), and adenosine triphosphate with remarkable enhancements of 231%, 30%, and 86%, compared with that of molecules mixing in aqueous solution. Additionally, the versatile PSNC enables simulation of light-independent reactions, achieving a controllable output of various target products. The regenerated NADH within PSNC further facilitates alcohol dehydrogenase, yielding methanol with a notable efficiency improvement of 37%. This work introduces a promising platform for sustainable solar energy conversion and the simultaneous synthesis of multiple valuable products in an ingenious and straightforward way.

Utilizing microbial metabolite in catalytic cascade synthesis of conjugated oligomers for In-Situ regulation of biological activity.

Despite the advances of multistep enzymatic cascade reactions, their incorporation with abiotic reactions in living organisms remains challenging in synthetic biology. Herein, we combined microbial metabolic pathways and Pd-catalyzed processes for in-situ generation of bioactive conjugated oligomers. Our biocompatible one-pot coupling reaction utilized the fermentation process of engineered E. coli that converted glucose to styrene, which participated in the Pd-catalyzed Heck reaction for in-situ synthesis of conjugated oligomers. This process serves a great interest in understanding resistance evolution by utilizing the inhibitory activity of the synthesized conjugated oligomers. The approach allows for the in-situ combination of biological metabolism and CC coupling reactions, opening up new possibilities for the biosynthesis of unnatural molecules and enabling the in-situ regulation of the bioactivity of the obtained products.

Biosynthesis of Multifunctional Transformable Peptides for Inducing Tumor Cell Apoptosis.

Engineered nanomaterials hold great promise to improve the specificity of disease treatment. Herein, a fully protein-based material is obtained from nonpathogenic Escherichia coli (E. coli), which is capable of morphological transformation from globular to fibrous in situ for inducing tumor cell apoptosis. The protein-based material P1 is comprised of a ß-sheet-forming peptide KLVFF, pro-apoptotic protein BAK, and GFP along with targeting moieties. The self-assembled nanoparticles of P1 transform into nanofibers in situ in the presence of cathepsin B, and the generated nanofibrils favor the dimerization of functional BH3 domain of BAK on the mitochondrial outer membrane, leading to efficient anticancer activity both in vitro and in vivo via mitochondria-dependent apoptosis through Bcl-2 pathway. To precisely manipulate the morphological transformation of biosynthetic molecules in living cells, a spatiotemporally controllable anticancer system is constructed by coating P1-expressing E. coli with cationic conjugated polyelectrolytes to release the peptides in situ under light irradiation. The biosynthetic peptide-based enzyme-catalytic transformation strategy in vivo would offer a novel perspective for targeted delivery and shows great potential in precision disease therapeutics.

Organic Semiconductor-Organism Interfaces for Augmenting Natural and Artificial Photosynthesis.

Carbon neutrality is increasingly broadly recognized as a vehicle for climate action and sustainable development. Photosynthesis contributes to maintaining a suitable carbon-oxygen balance for survival and plays an irreplaceable role in mitigating the greenhouse effect. However, the energy conversion efficiency of photosynthesis is only about 1%, far below the theoretical maximum. With the ecological demand of carbon neutrality, it is wise and necessary to further improve the efficiency of photosynthesis. Among methods to do so, the most direct and original one is improving the utilization of photosynthetic pigments to the weak absorption region of the spectrum and thus enhancing the solar energy utilization efficiency.This Account summarizes our group's work on constructing conjugated polymer-photosynthetic organism interfaces to augment photosynthetic efficiency. Side chain modification of ionic groups or preparation of nanoparticles makes conjugated polymers water-soluble and electrically charged, which allows them to bind to the surface of photosynthetic microorganisms through electrostatic interactions or be absorbed by plant roots. Owing to the designable and unparalleled light capture and emission capabilities, funnel-like excitation energy transfer mode, and enviable biocompatibility, organic semiconductor conjugated polymers can be used as "artificial antennas" to make up for the lack of natural antenna pigments and expand the photosynthetically active radiation (PAR) range. With this strategy, we achieved enhancement of the photosynthetic efficiency of a broad range of organisms, including oxygenic photosynthetic organisms, from organelle to prokaryotic cyanobacteria, eukaryotic lower plants, and higher plants, as well as anoxygenic photosynthetic organisms. Unlike conventional semiconductors, conjugated polymers have not only electronic conductivity but also ionic conductivity, which is the main means of bioelectrical signal transduction. Therefore, they are able to act as "electron bridges" to accelerate the electron transfer rate at the material-organism interface. On this basis, we introduced conjugated polymers into artificial photosynthesis systems, including biological photovoltaics and artificial carbon sequestration, to increase energy conversion efficiency. These studies open a new frontier for functional studies of conjugated molecules and provide inspirations for the design of photosynthesis systems in the future.

Increased Nitrogenase Activity in Solar-Driven Biohybrids Containing Non-photosynthetic Bacteria and Conducting Polymers.

A conductive polymer-based photosynthetic biohybrid is constructed to enhance biological nitrogen fixation by increasing nitrogenase activity in the non-photosynthetic bacterium Azotobacter Chroococcum (A. Chroococcum). The light-harvesting cationic poly(fluorene-alt-phenylene) (PFP) electrostatically binds to the surface of the bacteria and possesses satisfactory conductivity to facilitate electron transfer to the bacterium, promoting the nitrogen fixation pathway through redox proteins on the surface of the bacteria when under illumination. Therefore, the nitrogenase activity, hydrogen, NH4 + -N and L-amino acids production are increased by 260 %, 37 %, 44 %, and 47 %, respectively. The expression levels of nifD and nifK encoding molybdenum-iron (MoFe) protein and relevant nitrogen-fixing proteins are up-regulated. These photoactive conductive polymer-bacteria biohybrids provide a new method for improving the biological nitrogen fixation capability of non-photosynthetic nitrogen-fixing bacteria.

Selective Fluorescence Imaging of Cancer Cells Based on ROS-Triggered Intracellular Cross-Linking of Artificial Enzyme.

Inside living cells, regulation of catalytic activity of artificial enzymes remains challenging due to issues such as biocompatibility, efficiency, and stability of the catalyst, by which the practical applications of artificial enzymes have been severely hindered. Here, an artificial enzyme, PTT-SGH, with responsiveness to reactive oxygen species (ROS), was obtained by introducing a catalytic histidine residue to pentaerythritol tetra(3-mercaptopropionate) (PTT). The artificial enzyme formed large aggregates in cells via the intracellular ROS-mediated oxidation of thiol groups. The process was significantly facilitated in tumor cells because of the higher ROS concentration in the tumor microenvironment. The catalytic activity of this artificial enzyme was intensively enhanced through deprotonation of cross-linked PTT-SGH, which showed typical esterase activities. Selective fluorescence imaging of tumor cells was achieved using the artificial enzyme to trigger the cleavage of the ester bond of the caged fluorophore inside living cells.

Supramolecular Regulation of Catalytic Activity for an Amphiphilic Pyrene-Ruthenium Complex in Water.

A switchable catalytic system has been designed and constructed with a host-guest interaction between cucurbituril (CB) and an amphiphilic metal complex pyrene-ruthenium (Py-Ru). Py-Ru can self-assemble into positively charged nanoparticles in water, and exhibits an enhanced catalytic efficiency in the transfer hydrogenation of NAD+ to NADH. After forming an inclusion complex with CB, Py-Ru aggregates are broken, leading to a decrease in catalytic efficiency, which can be recovered by competitive replacement with amantadine. This supramolecular strategy provides an efficient and flexible method for constructing reversible catalytic system, which also extends the application scope of the host-guest interaction.

In Situ Synthesis of Photoactive Polymers on a Living Cell Surface via Bio-Palladium Catalysis for Modulating Biological Functions.

Cell surface engineering with functional polymers is an effective strategy to modulate cell activity. Here, a bio-palladium catalyzed polymerization strategy was developed for in situ synthesis of conjugated polymers on living cell surfaces. Through Sonagashira polymerization, photoactive polyphenyleneethynylene (PPE) is synthesized on the cell surface via cell-generated bio-Pd catalyst. The in situ formed PPE is identified by excellent light-harvest capacity and blue fluorescence on the surfaces of E. coli and C. pyrenoidosa. Besides imaging microbes for tracing the polymerization process, PPE also exhibits enhanced antibacterial activity against E. coli. It can also augment the ATP synthesis of C. pyrenoidosa through enlarging the light absorption and accelerating the cyclic electron transport of the algae. With this bio-metal catalyzed polymerization method, functional polymers can be synthesized in situ on the living cell surface.

Water-Soluble Conjugated Organic Molecules as Optical and Electrochemical Materials for Interdisciplinary Biological Applications.

Apart from the wide applications in the field of electronic and optoelectronic devices, conjugated molecules have been established as useful functional materials for biological applications. By introducing hydrophilic side chains to conjugated backbones, water-soluble conjugated polymers or oligomers (CPs or COs) inherit the attractive optical and electronic properties from conjugated molecules, while their water solubility ensures interaction with biological substrates such as biomacromolecules, microorganisms, and living cells for further biological applications. Benefiting from high brightness, large extinction coefficients, excellent photostability, low cytotoxicity, stability in bodily fluids, and versatile structural modifications, water-soluble conjugated polymers and oligomers have offered powerful alternatives in a variety of biological applications including biological and chemical sensors, fluorescence imaging, disease diagnostics, and therapy. This Account will focus on our recent advances in design, synthesis, and interdisciplinary biological applications of a series of new water-soluble CP and CO materials, starting with a brief introduction to water-soluble CPs and COs and various methods and strategies developed for the preparation of advanced water-soluble CPs and COs. Since their properties can be tuned by rational design and synthesis at the level of the conjugated repeat unit and versatile pendant groups, CPs and COs provide a diverse toolbox for satisfying interdisciplinary biological applications. The application of water-soluble CPs and COs in the past five years can be broadly categorized into four areas. Specifically, integrating the unique optoelectronic properties of water-soluble CPs and COs with self-assembly and supramolecular strategies, efficacy regulation of antibiotic and anticancer drugs has been achieved, meanwhile drug resistance could be overcome and drug resistant "superbacteria" can be inhibited. For applications regulating cellular functions and biological processes, we introduce CPs and COs with the ability to regulate intracellular oxidative stress, cell-cell communication, cellular proliferation, cell membrane permeability, and quorum sensing of bacteria cells. By covalent linkage of reactive groups upon CPs and COs, these molecules are endowed with abilities like disassembly of amyloid polypeptides, biased distribution in cells, selective imaging of organelles, and distinguished interactions with biomolecules. For photothermal therapy (PTT) applications, photothermal-responsive conjugated polymer materials have been utilized for remote control of gene expression in living cells and in vivo photothermal therapy of cancer. Beyond these applications, we have achieved new interdisciplinary applications of water-soluble CP and CO materials for biological optoelectronic devices including photosynthesis, photocatalysis, and bioenergy. Specific features or properties of water-soluble CPs and COs are leveraged to bring opportunities for each of these applications. These studies open a new frontier for development of new functional conjugated molecule materials and provide better understanding of their interactions with biological systems as well as structure/property relationships. Current limitations confronted by CPs and COs are raised, and developmental direction for the future is proposed.

Biohybrid Conjugated Polymer Materials for Augmenting Energy Conversion of Bioelectrochemical Systems.

Bioelectrochemical systems (BESs) provide favorable opportunities for the sustainable conversion of energy from biological metabolism. Biological photovoltaics (BPVs) and microbial fuel cells (MFCs) respectively realize the conversion of renewable solar energy and bioenergy into electrical energy by utilizing electroactive biological extracellular electron transfer, however, along with this energy conversion progress, relatively poor durability and low output performance are challenges as well as opportunities. Advances in improving bio-electrode interface compatibility will help to solve the problem of insufficient performance and further have a far-reaching impact on the development of bioelectronics. Conjugated polymers (CPs) with specific optical and electrical properties (absorption and emission spectra, energy band structure and electrical conductivity) afforded by π-conjugated backbones are conducive to enhancing the electron generation and output capacity of electroactive organisms. Furthermore, the water solubility, functionality, biocompatibility and mechanical properties optimized through appropriate modification of side chain provide a more adaptive contact interface between biomaterials and electrodes. In this minireview, we summarize the prominent contributions of CPs in the aspect of augmenting the photovoltaic response of BPVs and power supply of MFCs, and specifically discussed the role of CPs with expectation to provide inspirations for the design of bioelectronic devices in the future.

Fluorescent and Biocompatible Ruthenium-Coordinated Oligo(p-phenylenevinylene) Nanocatalysts for Transfer Hydrogenation in the Mitochondria of Living Cells.

It is challenging to design metal catalysts for in situ transformation of endogenous biomolecules with good performance inside living cells. Herein, we report a multifunctional metal catalyst, ruthenium-coordinated oligo(p-phenylenevinylene) (OPV-Ru), for intracellular catalysis of transfer hydrogenation of nicotinamide adenine dinucleotide (NAD+ ) to its reduced format (NADH). Owing to its amphiphilic characteristic, OPV-Ru possesses good self-assembly capability in water to form nanoparticles through hydrophobic interaction and π-π stacking, and numerous positive charges on the surface of nanoparticles displayed a strong electrostatic interaction with negatively charged substrate molecules, creating a local microenvironment for enhancing the catalysis efficiency in comparison to dispersed catalytic center molecule (TOF value was enhanced by about 15 fold). OPV-Ru could selectively accumulate in the mitochondria of living cells. Benefiting from its inherent fluorescence, the dynamic distribution in cells and uptake behavior of OPV-Ru could be visualized under fluorescence microscopy. This work represents the first demonstration of a multifunctional organometallic complex catalyzing natural hydrogenation transformation in specific subcellular compartments of living cells with excellent performance, fluorescent imaging ability, specific mitochondria targeting and good chemoselectivity with high catalysis efficiency.

Development of A Thermo-Responsive Conjugated Polymer with Photobleaching-Resistance Property and Tunable Photosensitizing Performance.

A thermo-responsive conjugated polymer, PFBT-gPA is synthesized by grafting the poly(N-isopropylacrylamide) (PNIPAAm) to the side chains of a conjugated polyfluorene derivative through atom transfer radical polymerization (ATRP). PFBT-gPA undergoes a reversible phase transition in water below and above the lower critical solution temperature (LCST) and the process is studied by differential scanning calorimetry (DSC) analysis and UV/vis absorption spectra. PFBT-gPA shows a good photostability under UV light irradiation especially above the LCST. Moreover, the photosensitizing performance of PFBT-gPA could be tuned simply by changing temperature. The unique properties of PFBT-gPA promise its potential applications in sensing and photodynamic therapy.

Solar-Powered Organic Semiconductor-Bacteria Biohybrids for CO2 Reduction into Acetic Acid.

An organic semiconductor-bacteria biohybrid photosynthetic system is used to efficiently realize CO2 reduction to produce acetic acid with the non-photosynthetic bacteria Moorella thermoacetica. Perylene diimide derivative (PDI) and poly(fluorene-co-phenylene) (PFP) were coated on the bacteria surface as photosensitizers to form a p-n heterojunction (PFP/PDI) layer, affording higher hole/electron separation efficiency. The π-conjugated semiconductors possess excellent light-harvesting ability and biocompatibility, and the cationic side chains of organic semiconductors could intercalate into cell membranes, ensuring efficient electron transfer to bacteria. Moorella thermoacetica can thus harvest photoexcited electrons from the PFP/PDI heterojunction, driving the Wood-Ljungdahl pathway to synthesize acetic acid from CO2 under illumination. The efficiency of this organic biohybrid is about 1.6 %, which is comparable to those of reported inorganic biohybrid systems.

Design of an Amphiphilic Perylene Diimide for Optical Recognition of Anticancer Drug through a Chirality-Induced Helical Structure.

Introduction of chirality into a supramolecular self-assembly system plays an indispensable role in attaining specific molecular recognition ability. Herein, a chiral anticancer drug 5'-deoxy-5-fluorouridine (5'DFU) was explored for inducing the self-assembly of a cationic perylene diimide derivative containing boronic acid groups (PDI-PBA) into a highly ordered right-handed helical structure. As a result, PDI-PBA exhibited a molecular recognition ability towards 5'DFU among other cis-diols and anticancer drugs. With the help of a dynamic covalent bond and favorable hydrogen-bonding interactions, chirality transfer from chiral 5'DFU to achiral PDI-PBA breaks down the strong π-π stacking of PDI-PBA and makes it reorganize into highly ordered helical supramolecular structures. This work provides an insight into chiral anticancer drug tuning interactions of π-chromophores and the inducement of hierarchical self-assembly to achieve specific molecular recognition.

Luminescent, Oxygen-Supplying, Hemoglobin-Linked Conjugated Polymer Nanoparticles for Photodynamic Therapy.

Photodynamic therapy (PDT) is a promising method for cancer treatment. Two parameters that influence the efficacy of PDT are the light source and oxygen supply. Herein, we prepared a system for PDT using hemoglobin (Hb)-linked conjugated polymer nanoparticles (CPNs), which can luminesce and supply oxygen. Hb catalyzes the activation of luminol, the conjugated polymer poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV) nanoparticles can absorb the chemiluminescence of luminol through chemiluminescence resonance energy transfer (CRET) and then sensitize the oxygen supplied by Hb to produce reactive oxygen species that kill cancer cells. This system could be used for the controlled release of an anticancer prodrug. The system does not need an external light source and circumvents the insufficient level molecular oxygen under hypoxia. This work provides a proof-of-concept to explore smart and multifunctional nanoplatforms for phototherapy.

Reactive Amphiphilic Conjugated Polymers for Inhibiting Amyloid ß Assembly.

Protein misfolding and aberrant aggregations are associated with multiple prevalent and intractable diseases. Inhibition of amyloid assembly is a promising strategy for the treatment of amyloidosis. Reported here is the design and synthesis of a reactive conjugated polymer, a poly(p-phenylene vinylene) derivative, functionalized with p-nitrophenyl esters (PPV-NP) and it inhibits the assembly of amyloid proteins, degrades preformed fibrils, and reduces the cytotoxicity of amyloid aggregations in living cells. PPV-NP is attached to the proteins through hydrophobic interactions and irreversible covalent linkage. PPV-NP also exhibited the capacity to eliminate Aß plaques in brain slices in ex vivo assays. This work represents an innovative attempt to inhibit protein pathogenic aggregates, and may offer insights into the development of therapeutic strategies for amyloidosis.

Electrochemiluminescence for Electric-Driven Antibacterial Therapeutics.

The employment of physical light sources in clinical photodynamic therapy (PDT) system endows it with a crucial defect in the treatment of deeper tissue lesions due to the limited penetration depth of light in biological tissues. In this work, we constructed for the first time an electric driven luminous system based on electrochemiluminescence (ECL) for killing pathogenic bacteria, where ECL is used for the excitation of photosensitizer instead of a physical light source to produce reactive oxygen species (ROS). We named this new strategy as ECL-therapeutics. The mechanism for the ECL-therapeutics is dependent on the perfect spectral overlap and energy transfer from the ECL generated by luminol to photosensitizer, cationic oligo(p-phenylenevinylene) (OPV), to sensitize the surrounding oxygen molecule into ROS. Furthermore, taking into account the practical application of our ECL-therapeutics, we used flexible hydrogel to replace the liquid system to develop hydrogel antibacterial device. Because the chemical reaction is a slow process in the hydrogel, the luminescence could last for more than 10 min after only electrifying for five seconds. This unique persistent luminescence characteristic with long afterglow life makes them suitable for persistent antibacterial applications. Thus, stretchable and persistent hydrogel devices are designed by integrating stretchable hydrogel, persistent ECL and antibacterial function into hydrogel matrices. This novel strategy avoids the employment of external light source, making it simple, convenient and controllable, which exploits a new field for ECL beyond sensors and also opens up a new model for PDT.

Supramolecular Strategy Based on Conjugated Polymers for Discrimination of Virus and Pathogens.

A conjugated polymer-based supramolecular system is designed for discrimination of virus and microbes. The supramolecular system is composed of cationic polythiophene derivative (PT) and barrel-shaped macrocyclic molecular cucurbit[7]uril (CB[7]). Because PT and PT/CB[7] complexes possess different interaction manners toward virus and microbes, the rapid and simple discrimination of virus and microbes was realized through polymer fluorescence intensity change assisting with standard linear discriminant analysis (LDA). The supramolecular strategy would expand the idea of designing biological probes and further promote the extensive application of conjugated polymer materials in biosensor field.

Conjugated Polymer Nanoparticles with Appended Photo-Responsive Units for Controlled Drug Delivery, Release, and Imaging.

Carriers that can afford tunable physical and structural changes are envisioned to address critical issues in controlled drug delivery applications. Herein, photo-responsive conjugated polymer nanoparticles (CPNs) functionalized with donor-acceptor Stenhouse adduct (DASA) and folic acid units for controlled drug delivery and imaging are reported. Upon visible-light (λ=550 nm) irradiation, CPNs simultaneously undergo structure, color, and polarity changes that release encapsulated drugs into the cells. The backbone of CPNs favors FRET to DASA units boosting their fluorescence. Notably, drug-loaded CPNs exhibit excellent biocompatibility in the dark, indicating perfect control of the light trigger over drug release. Delivery of both hydrophilic and hydrophobic drugs with good loading efficiency was demonstrated. This strategy enables remotely controlled drug delivery with visible-light irradiation, which sets an example for designing delivery vehicles for non-invasive therapeutics.

Supramolecular Conjugated Polymer Systems with Controlled Antibacterial Activity.

Infections of antibiotic-resistant pathogens have caused a series of public health crises across the world. According to the latest published reports, an antibiotic switch has been recognized as a potential strategy to control antibacterial activity for combating this serious drug resistance. Thus, it is anticipated that more effective antibiotic switches should be obtained by further exploring the developed strategies. Here, we report an improved pretreatment strategy using a surfactant (Triton X-100) for constructing an effective supramolecular antibiotic switch based on a poly(fluorene-co-phenylene) derivative (PFP) and cucurbit[7]uril (CB[7]), which can regulate the aggregation state of polymers before the supramolecular self-assembly process occurs. Triton X-100 can regulate the aggregation states of conjugated polymers, which is used to successfully realize the reversible control of bactericidal activity of PFP in the dark and under white light irradiation by supramolecular assembly/disassembly between PFP and CB[7]. Specialized antibiotic switches are significantly important to fight pathogenic infections and solve the drug resistance crisis in the future.