Metabolic Regulation-Mediated Reversion of the Tumor Immunosuppressive Microenvironment for Potentiating Cooperative Metabolic Therapy and Immunotherapy.

Tumor cells exhibit heightened glucose (Glu) consumption and increased lactic acid (LA) production, resulting in the formation of an immunosuppressive tumor microenvironment (TME) that facilitates malignant proliferation and metastasis. In this study, we meticulously engineer an antitumor nanoplatform, denoted as ZLGCR, by incorporating glucose oxidase, LA oxidase, and CpG oligodeoxynucleotide into zeolitic imidazolate framework-8 that is camouflaged with a red blood cell membrane. Significantly, ZLGCR-mediated consumption of Glu and LA not only amplifies the effectiveness of metabolic therapy but also reverses the immunosuppressive TME, thereby enhancing the therapeutic outcomes of CpG-mediated antitumor immunotherapy. It is particularly important that the synergistic effect of metabolic therapy and immunotherapy is further augmented when combined with immune checkpoint blockade therapy. Consequently, this engineered antitumor nanoplatform will achieve a cooperative tumor-suppressive outcome through the modulation of metabolism and immune responses within the TME.

Immunostimulant Hydrogel-Guided Tumor Microenvironment Reprogramming to Efficiently Potentiate Macrophage-Mediated Cellular Phagocytosis for Systemic Cancer Immunotherapy.

Macrophage-mediated cellular phagocytosis (MMCP) plays a critical role in conducting antitumor immunotherapy but is usually impaired by the intrinsic phagocytosis evading ability of tumor cells and the immunosuppressive tumor microenvironment (TME). Herein, a MMCP-boosting hydrogel (TCCaGM) was elaborately engineered by encapsulating granulocyte-macrophage colony-stimulating factor (GM-CSF) and a therapeutic nanoplatform (TCCaN) that preloaded with the tunicamycin (Tuni) and catalase (CAT) with the assistance of CaCO3 nanoparticles (NPs). Strikingly, the hypoxic/acidic TME was efficiently alleviated by the engineered hydrogel, "eat me" signal calreticulin (CRT) was upregulated, while the "don't eat me" signal CD47 was downregulated on tumor cells, and the infiltrated DCs were recruited and activated, all of which contributed to boosting the macrophage-mediated phagocytosis and initiating tumor-specific CD8+ T cells responses. Meanwhile, the remodeled TME was beneficial to accelerate the polarization of tumor-associated macrophages (TAMs) to the antitumoral M1-like phenotype, further heightening tumoricidal immunity. With the combination of PD-1 antibody (αPD-1), the designed hydrogel significantly heightened systemic antitumor immune responses and long-term immunological effects to control the development of primary and distant tumors as well as suppress tumor metastasis and recurrence, which established an optimal strategy for high-performance antitumor immunotherapy.

Fused Cytomembrane-Camouflaged Nanoparticles for Tumor-Specific Immunotherapy.

Tumor immunotherapy is commonly hindered by inefficient delivery and presentation of tumor antigens as well as immunosuppressive tumor microenvironment. To overcome these barriers, a tumor-specific nanovaccine capable of delivering tumor antigens and adjuvants to antigen-presenting cells and modulating the immune microenvironment to elicit strong antitumor immunity is reported. This nanovaccine, named FCM@4RM, is designed by coating the nanocore (FCM) with a bioreconstituted cytomembrane (4RM). The 4RM, which is derived from fused cells of tumorous 4T1 cells and RAW264.7 macrophages, enables effective antigen presentation and stimulation of effector T cells. FCM is self-assembled from Fe(II), unmethylated cytosine-phosphate-guanine oligodeoxynucleotide (CpG), and metformin (MET). CpG, as the stimulator of toll-like receptor 9, induces the production of pro-inflammatory cytokine and the maturation of cytotoxic T lymphocytes (CTLs), thereby enhancing antitumor immunity. Meanwhile, MET functions as the programmed cell death ligand 1 inhibitor and can restore the immune responses of T cells against tumor cells. Therefore, FCM@4RM exhibits high targeting capabilities toward homologous tumors that develop from 4T1 cells. This work offers a paradigm for developing a nanovaccine that systematically regulates multiple immune-related processes to achieve optimal antitumor immunotherapy.

Specific activation of cGAS-STING pathway by nanotherapeutics-mediated ferroptosis evoked endogenous signaling for boosting systemic tumor immunotherapy.

Activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway could effectively initiate antitumor immunity, but specific activation of STING pathway is still an enormous challenge. Herein, a ferroptosis-induced mitochondrial DNA (mtDNA)-guided tumor immunotherapy nanoplatform (designated as HBMn-FA) was elaborately developed for activating and boosting STING-based immunotherapy. On the one hand, the high-levels of reactive oxygen species (ROS) in tumor cells induced by HBMn-FA-mediated ferroptosis elicited mitochondrial stress to cause the release of endogenous signaling mtDNA, which specifically initiate cGAS-STING pathway with the cooperation of Mn2+. On the other hand, the tumor-derived cytosolic double-stranded DNA (dsDNA) from debris of death cells caused by HBMn-FA further activated the cGAS-STING pathway in antigen-presenting cells (e.g., DCs). This bridging of ferroptosis and cGAS-STING pathway could expeditiously prime systemic antitumor immunity and enhance the therapeutic efficacy of checkpoint blockade to suppress tumor growth in both localized and metastatic tumor models. The designed nanotherapeutic platform paves the way for novel tumor immunotherapy strategies that are based on specific activation of STING pathway.

Interference of Glucose Bioavailability of Tumor by Engineered Biohybrids for Potentiating Targeting and Uptake of Antitumor Nanodrugs.

The chemotherapy efficacy of nanodrugs is restricted by poor tumor targeting and uptake. Here, an engineered biohybrid living material (designated as EcN@HPB) is constructed by integrating paclitaxel and BAY-876 bound human serum albumin nanodrugs (HPB) with Escherichia coli Nissle 1917 (EcN). Due to the inherent tumor tropism of EcN, EcN@HPB could actively target the tumor site and competitively deprive glucose through bacterial respiration. Thus, albumin would be used as an alternative nutrient source for tumor metabolism, which significantly promotes the internalization of HPB by tumor cells. Subsequently, BAY-876 internalized along with HPB nanodrugs would further depress glucose uptake of tumor cells via inhibiting glucose transporter 1 (GLUT1). Together, the decline of glucose bioavailability of tumor cells would activate and promote the macropinocytosis in an AMP-activated protein kinase (AMPK)-dependent manner, resulting in more uptake of HPB by tumor cells and boosting the therapeutic outcome of paclitaxel.

Essential thrombocythemia with non-ST-segment elevation myocardial infarction as the first manifestation: A case report.

BACKGROUND: We report a case of essential thrombocythemia (ET) in a 44-year-old male who exhibited non-ST-segment-elevation myocardial infarction (NSTEMI) as the first manifestation without known cardiovascular risk factors (CVRFs). For the first time, we reported a left main trifurcation lesion in NSTEMI caused by ET, including continuous stenosis lesions from the left main to the ostial left anterior descending (LAD) artery and an obvious thrombotic lesion in the ostial and proximal left circumflex (LCX) artery. There was 60% diffuse stenosis in the left main (LM) that extended to the ostial LAD, thrombosis of the ostial LAD and proximal LCX, and 90% stenosis in the proximal LCX. During the operation, thrombus aspiration was performed, but no obvious thrombus was aspirated. Performing the kissing balloon technique (KBT) in the LCX and LM unexpectedly increased the narrowness of the LAD. Then, the single-stent crossover technique, final kissing balloon technique and proximal optimization technique (POT) were performed. On the second day after percutaneous coronary intervention (PCI), the number of platelets (PLTs) still increased significantly to as high as 696 × 109/L. The bone marrow biopsy done later, together with JAK2 (exon 14) V617F mutation, confirms the diagnosis of ET. Hydroxyurea was administered to inhibit bone marrow proliferation to control the number of PLTs. CASE SUMMARY: A 44-year-old male patient went to a local hospital for treatment for intermittent chest pain occurring over 8 h. The examination at the local hospital revealed elevated cTnI and significantly elevated platelet. Then, he was diagnosed with acute myocardial infarction and transferred to our hospital for emergency interventional treatment by ambulance. During the operation, thrombus aspiration, the single-stent crossover technique, final kissing balloon technique and POT were performed. Dual antiplatelet therapy comprising aspirin and ticagrelor was used after PCI. Evidence of mutated JAK2 V617F and bone marrow biopsy shown the onset of ET. Together with JAK2 (exon 14) V617F mutation, ET was diagnosed according to the World Health Organization (WHO) diagnostic criteria, and the patient was placed on hydroxyurea. During the one-year postoperative period, repeated examinations showed a slight increase in PLTs, but the patient no longer had chest tightness, chest pain or bleeding or developed new thromboembolisms. CONCLUSION: Routine physical examinations and screenings are conducive to the early detection of ET, and the risk for thrombosis should be assessed. Then, active antiplatelet therapy and myelosuppression therapy should be used for high-risk ET patients.

Biomedical polymers: synthesis, properties, and applications.

Biomedical polymers have been extensively developed for promising applications in a lot of biomedical fields, such as therapeutic medicine delivery, disease detection and diagnosis, biosensing, regenerative medicine, and disease treatment. In this review, we summarize the most recent advances in the synthesis and application of biomedical polymers, and discuss the comprehensive understanding of their property-function relationship for corresponding biomedical applications. In particular, a few burgeoning bioactive polymers, such as peptide/biomembrane/microorganism/cell-based biomedical polymers, are also introduced and highlighted as the emerging biomaterials for cancer precision therapy. Furthermore, the foreseeable challenges and outlook of the development of more efficient, healthier and safer biomedical polymers are discussed. We wish this systemic and comprehensive review on highlighting frontier progress of biomedical polymers could inspire and promote new breakthrough in fundamental research and clinical translation.

A Self-Driven Bioreactor Based on Bacterium-Metal-Organic Framework Biohybrids for Boosting Chemotherapy via Cyclic Lactate Catabolism.

The excessive lactate in the tumor microenvironment always leads to poor therapeutic outcomes of chemotherapy. In this study, a self-driven bioreactor (defined as SO@MDH, where SO is Shewanella oneidensis MR-1 and MDH is MIL-101 metal-organic framework nanoparticles/doxorubicin/hyaluronic acid) is rationally constructed via the integration of doxorubicin (DOX)-loaded metal-organic framework (MOF) MIL-101 nanoparticles with SO to sensitize chemotherapy. Owing to the intrinsic tumor tropism and electron-driven respiration of SO, the biohybrid SO@MDH could actively target and colonize hypoxic and eutrophic tumor regions and anaerobically metabolize lactate accompanied by the transfer of electrons to Fe3+, which is the key component of the MIL-101 nanoparticles. As a result, the intratumoral lactate would undergo continuous catabolism coupled with the reduction of Fe3+ to Fe2+ and the subsequent degradation of MIL-101 frameworks, leading to an expeditious drug release for effective chemotherapy. Meanwhile, the generated Fe2+ will be promptly oxidized by the abundant hydrogen peroxide in the tumor microenvironment to reproduce Fe3+, which is, in turn, beneficial to circularly catabolize lactate and boost chemotherapy. More importantly, the consumption of intratumoral lactic acid could significantly inhibit the expression of multidrug resistance-related ABCB1 protein (also named P-glycoprotein (P-gp)) for conquering drug-resistant tumors. SO@MDH demonstrated here holds high tumor specificity and promising chemotherapeutic efficacy for suppressing tumor growth and overcoming multidrug resistance, confirming its potential prospects in cancer therapy.

A tumor-cell biomimetic nanoplatform embedding biological enzymes for enhanced metabolic therapy.

A tumor cell membrane-camouflaged therapeutic system was fabricated to eliminate tumors by embedding apyrase and glucose oxidase (GOx) into zeolitic imidazolate framework-8 (ZIF-8) nanoparticles for tumor-targeted metabolic therapy. Experimental results demonstrated that these functional nanoparticles could disturb the energy supply of tumor cells by depleting ATP and glucose and efficiently induce tumor cell death.

Recent Advances in Engineered Materials for Immunotherapy-Involved Combination Cancer Therapy.

Immunotherapy that can activate immunity or enhance the immunogenicity of tumors has emerged as one of the most effective methods for cancer therapy. Nevertheless, single-mode immunotherapy is still confronted with several critical challenges, such as the low immune response, the low tumor infiltration, and the complex immunosuppression tumor microenvironment. Recently, the combination of immunotherapy with other therapeutic modalities has emerged as a powerful strategy to augment the therapeutic outcome in fighting against cancer. In this review, recent research advances of the combination of immunotherapy with chemotherapy, phototherapy, radiotherapy, sonodynamic therapy, metabolic therapy, and microwave thermotherapy are summarized. Critical challenges and future research direction of immunotherapy-based cancer therapeutic strategy are also discussed.

Mechatronics design and testing of a cable-driven upper limb rehabilitation exoskeleton with variable stiffness.

In this paper, we present a cable-driven exoskeleton with variable stiffness for upper limb rehabilitation. Adjustable stiffness of the cable-driven exoskeleton is achieved by attaching a novel variable stiffness module (VSM) to each driving cable. The module is able to vary stiffness in a large range through changing cable tension. In this paper, a stiffness model is developed for a cable-driven exoskeleton to reveal the stiffness performance of the exoskeleton with the influence of VSMs. Based on the stiffness model, a controller with stiffness-oriented strategy is proposed to vary the stiffness of the exoskeleton. Experiments on a prototype of a cable-driven exoskeleton are conducted to validate the controller.

Cell primitive-based biomimetic functional materials for enhanced cancer therapy.

Cell primitive-based functional materials that combine the advantages of natural substances and nanotechnology have emerged as attractive therapeutic agents for cancer therapy. Cell primitives are characterized by distinctive biological functions, such as long-term circulation, tumor specific targeting, immune modulation etc. Moreover, synthetic nanomaterials featuring unique physical/chemical properties have been widely used as effective drug delivery vehicles or anticancer agents to treat cancer. The combination of these two kinds of materials will catalyze the generation of innovative biomaterials with multiple functions, high biocompatibility and negligible immunogenicity for precise cancer therapy. In this review, we summarize the most recent advances in the development of cell primitive-based functional materials for cancer therapy. Different cell primitives, including bacteria, phages, cells, cell membranes, and other bioactive substances are introduced with their unique bioactive functions, and strategies in combining with synthetic materials, especially nanoparticulate systems, for the construction of function-enhanced biomaterials are also summarized. Furthermore, foreseeable challenges and future perspectives are also included for the future research direction in this field.

Modelling Photosynthesis with ZnII -Protoporphyrin All-DNA G-Quadruplex/Aptamer Scaffolds.

All-DNA scaffolds act as templates for the organization of photosystem I model systems. A series of DNA templates composed of ZnII -protoporphyrin IX (ZnII PPIX)-functionalized G-quadruplex conjugated to the 3'- or 5'-end of the tyrosinamide (TA) aptamer and ZnII PPIX/G-quadruplex linked to the 3'- and 5'-ends of the TA aptamer through a four-thymidine bridge. Effective photoinduced electron transfer (ET) from ZnII PPIX/G-quadruplex to bipyridinium-functionalized tyrosinamide, TA-MV2+ , bound to the TA aptamer units is demonstrated. The effectiveness of the primary ET quenching of ZnII PPIX/G-quadruplex by TA-MV2+ controls the efficiency of the generation of TA-MV+. . The photosystem-controlled formation of TA-MV+. by the different photosystems dictates the secondary activation of the ET cascade corresponding to the ferredoxin-NADP+ reductase (FNR)-catalysed reduction of NADP+ to NADPH by TA-MV+. , and the sequestered alcohol dehydrogenase catalysed reduction of acetophenone to 1-phenylethanol by NADPH.

MicroRNA-Guided Selective Release of Loads from Micro-/Nanocarriers Using Auxiliary Constitutional Dynamic Networks.

Two different drug micro-carriers consisting of doxorubicin-dextran (DOX-D)- and camptothecin-modified carboxymethyl cellulose (CPT-CMC)-loaded nucleic acid-stabilized microcapsules, MC-1 and MC-2, or two different nanocarriers consisting of nucleic-acid-locked doxorubicin (DOX)- and camptothecin (CPT)-loaded metal-organic framework nanoparticles, NMOF-1 and NMOF-2, are coupled to auxiliary constitutional dynamic networks, CDNs, for the triggered release of the drugs. CDN "S" composed of four constituents AA'', AB', BA', and BB', and two hairpin structures, H1 and H2, leads to the CDN "S"-guided unlocking of the MC-1/MC-2 carriers and the release of DOX-D and CPT-CMC or of the NMOF-1 and NMOF-2 carriers that release DOX and CPT, respectively. The unlocking processes are activated by the cleavage of H1 and H2 by BB' and BA', respectively, to yield fragmented strands that unlock the gating units of the microcapsules/NMOFs carriers. In the presence of miRNA-155 or miRNA-124, dictated orthogonal reconfiguration of CDN "S" into CDN "X" or "Y" proceeds. The miRNA-155 stimulates the reconfiguration of CDN "S" to CDN "X", where AA' and BB' are upregulated, and AB' and BA' are downregulated, leading to the enhanced release of DOX-D or DOX from the microcapsule/NMOFs carriers, and to the concomitant inhibition of the release of CPT-CMC or CPT from the respective carriers. Similarly, the miRNA-124-triggered reconfiguration of CDN "S" to CDN "Y" results in the BA'-guided cleavage of H2 and the preferred release of CPT-CMC or CPT from the respective carriers. The miRNA-triggered CDN-driven unlocking of the carriers stimulates the amplified and selective release of the drugs from the microcapsules/NMOFs carriers.

100th Anniversary of Macromolecular Science Viewpoint: Poly(N-isopropylacrylamide)-Based Thermally Responsive Micelles.

Poly(N-isopropylacrylamide) (PNIPAAm)-based thermally responsive micelles are of great importance as smart materials for a number of applications such as drug delivery and biosensing, owing to their tunable lower critical solution temperature (LCST). Their design and synthesis in the nanoscale size range have been widely studied, and research interest in their structural and physic-chemical properties is continually growing. In this Viewpoint, representative research on the construction of PNIPAAm-based thermally responsive micelles as well as their applications are highlighted and discussed, which would serve as a good start for newcomers in this field and a positive guide for future research.

Thrombin Aptamer-Modified Metal-Organic Framework Nanoparticles: Functional Nanostructures for Sensing Thrombin and the Triggered Controlled Release of Anti-Blood Clotting Drugs.

This paper features the synthesis of thrombin-responsive, nucleic acid-gated, UiO-68 metal-organic framework nanoparticles (NMOFs) loaded with the drug Apixaban or rhodamine 6G as a drug model. Apixaban acts as an inhibitor of blood clots formation. The loads in the NMOFs are locked by duplex nucleic acids that are composed of anchor nucleic acids linked to the NMOFs that are hybridized with the anti-thrombin aptamer. In the presence of thrombin, the duplex gating units are separated through the formation of thrombin-aptamer complexes. The unlocking of the NMOFs releases the drug (or the drug model). The release of the drug is controlled by the concentration of thrombin. The Apixaban-loaded NMOFs revealed improved inhibition, as compared to free Apixaban, toward blood clot formation. This is reflected by their longer time intervals for inducing clot formation and the decreased doses of the drug required to affect clots formation. The beneficial effects of the Apixaban-loaded NMOFs are attributed to the slow-release mechanism induced by the NMOFs carriers, where the inhibition of factor Xa in the blood clotting cycle retards the formation of thrombin, which slows down the release of the drug.

Photosensitized H2 Evolution and NADPH Formation by Photosensitizer/Carbon Nitride Hybrid Nanoparticles.

The broadband C3N4 semiconductor absorbs in the UV region, λ = 330-380 nm, a feature limiting its application for light-to-energy conversion. The unique surface adsorption properties of C3N4 allow, however, the binding of a photosensitizer, operating in the visible-solar spectrum to the surface of C3N4. Coupling of the energy levels of the photosensitizer with the energy levels of C3N4 allows effective photoinduced electron-transfer quenching and subsequent charge separation in the hybrid structures. Two methods to adsorb a photosensitizer on the C3N4 nanoparticles are described. One is exemplified by the adsorption of Zn(II)-protoporphyrin IX on C3N4 using π-π interactions. The second method utilizes the specific binding interactions of single-stranded nucleic acids on C3N4 and involves the binding of a Ru(II)-tris-bipyridine-modified nucleic acid on the C3N4 nanoparticles. Effective electron-transfer quenching of the photoexcited photosensitizers by C3N4 proceeds in the two hybrid systems. The two hybrid photosystems induce the effective photosensitized reduction of N,N'-dimethyl-4,4'-bipyridinium, MV2+, to MV+•, in the presence of Na2EDTA as a sacrificial electron donor. The generation of MV+• is ca. 5-fold higher as compared to the formation of MV+• in the presence of the photosensitizer alone (in the absence of C3N4). The effective generation of MV+• in the photosystems is attributed to the efficient quenching of the photosensitizers, followed by effective charge separation of the electrons in the conduction band of C3N4 and the holes in the oxidized photosensitizer. The subsequent transfer of the conduction-band electrons to MV2+ and the oxidation of Na2EDTA by the oxidized photosensitizers lead to the effective formation of MV+•. The photogenerated MV+• by the two hybrid photosystems is used to catalyze H2 evolution in the presence of Pt nanoparticle catalysts and to mediate the reduction of NADP+ to NADPH, in the presence of ferredoxin-NADP+ reductase, FNR. The ability to couple the photogenerated NADPH to drive NADP+-dependent biocatalytic transformations is demonstrated.

Knee exoskeleton enhanced with artificial intelligence to provide assistance-as-needed.

Robotic therapy is a useful method applied during rehabilitation of stroke patients (to regain motor functions). To ensure active participation of the patient, assistance-as-needed is provided during robotic training. However, most existing studies are based on a predetermined desired trajectory, which significantly limits the use of this method for more complex scenarios. In this paper, artificial intelligence (AI) agents are introduced to enhance the robot so that a knee exoskeleton can be autonomously controlled. A new assist-as-needed (AAN) method is proposed, where the subjects and agents cooperatively control movements. An electromyographic (EMG)-controlled knee exoskeleton with an interesting screen game is developed. Two different AI agents, modular pipeline and deep Q-network, are introduced; both can control the exoskeleton to play the screen game independently. The human-robot cooperative control is studied with two different assistant strategies, i.e., fixed assistant ratio and AAN. Eight healthy subjects participated in the initial experiment, and four assistant modes were studied. The game scores obtained by the two agents were significantly higher than those obtained by healthy subjects (EMG control), indicating that using the agents to assist stroke rehabilitation is possible. The AAN method demonstrated a better performance than the fixed assistant ratio method, indicated by the higher integral muscle activation level and participant score. Compared to a fully active control (EMG control) and fully fixed guidance (AI control), human-robot cooperative control had significantly higher integral muscle activation levels, i.e., the subjects were more involved and motivated during training. Using AI agents to power rehabilitation robots is a promising way to realize AAN rehabilitation.

Development of an EMG-Controlled Knee Exoskeleton to Assist Home Rehabilitation in a Game Context.

As a leading cause of loss of functional movement, stroke often makes it difficult for patients to walk. Interventions to aid motor recovery in stroke patients should be carried out as a matter of urgency. However, muscle activity in the knee is usually too weak to generate overt movements, which poses a challenge for early post-stroke rehabilitation training. Although electromyography (EMG)-controlled exoskeletons have the potential to solve this problem, most existing robotic devices in rehabilitation centers are expensive, technologically complex, and allow only low training intensity. To address these problems, we have developed an EMG-controlled knee exoskeleton for use at home to assist stroke patients in their rehabilitation. EMG signals of the subject are acquired by an easy-to-don EMG sensor and then processed by a Kalman filter to control the exoskeleton autonomously. A newly-designed game is introduced to improve rehabilitation by encouraging patients' involvement in the training process. Six healthy subjects took part in an initial test of this new training tool. The test showed that subjects could use their EMG signals to control the exoskeleton to assist them in playing the game. Subjects found the rehabilitation process interesting, and they improved their control performance through 20-block training, with game scores increasing from 41.3 ± 15.19 to 78.5 ± 25.2. The setup process was simplified compared to traditional studies and took only 72 s according to test on one healthy subject. The time lag of EMG signal processing, which is an important aspect for real-time control, was significantly reduced to about 64 ms by employing a Kalman filter, while the delay caused by the exoskeleton was about 110 ms. This easy-to-use rehabilitation tool has a greatly simplified training process and allows patients to undergo rehabilitation in a home environment without the need for a therapist to be present. It has the potential to improve the intensity of rehabilitation and the outcomes for stroke patients in the initial phase of rehabilitation.

Artificial Photosynthesis with Electron Acceptor/Photosensitizer-Aptamer Conjugates.

Sequence-specific aptamers act as functional scaffolds for the assembly of photosynthetic model systems. The Ru(II)-tris-bipyridine photosensitizer is conjugated by different binding modes to the antityrosinamide aptamer to yield a set of photosensitizer-aptamer binding scaffolds. The N-methyl-N'-(3-aminopropane)-4,4'-bipyridinium electron acceptor, MV2+, is covalently linked to tyrosinamide, TA, to yield the conjugate TA-MV2+. The tyrosinamide unit in TA-MV2+ acts as a ligand for anchoring TA-MV2+ to the Ru(II)-tris-bipyridine-aptamer scaffold, generating the diversity of photosensitizer-aptamer/electron acceptor supramolecular conjugates. Effective electron transfer quenching in the photosynthetic model systems is demonstrated, and the quenching efficiencies are controlled by the structural features of the conjugates. The redox species generated by the photosensitizer-aptamer/electron acceptor supramolecular systems mediate the ferredoxin-NADP+ reductase, FNR, catalyzed synthesis of NADPH, and the Pt-nanoparticle-catalyzed evolution of hydrogen (H2). The novelty of the study rests on the unprecedented use of aptamer scaffolds as functional units for organizing photosynthetic model systems.