Porphyrin Cholesterol Conjugates for Enhanced Photodynamic Immunotherapy toward Lung Cancer.

Lung cancer is the major cause of cancer death worldwide. Immune checkpoint inhibitors (ICIs) of PD-1/PD-L1 have improved the survival rate in some patients with lung cancer. However, the efficacy of ICIs is limited by the inhibitory tumor immune microenvironment. Herein, we designed porphyrin cholesterol conjugates (TPPC) for synergistic photodynamic therapy (PDT)-immunotherapy for lung cancer. Porphyrin derivatives with great reactive oxygen species (ROS) production efficiency have been applied as photosensitizers in clinics, and cholesterol is one of the main components of the cell membrane. Porphyrin cholesterol conjugates could assemble into nanoparticles (NPs) in the absence of surfactants or amphiphilic polymers. On the other hand, TPPC NP-mediated PDT could accumulate at the tumor site and induce immunogenic cell death to stimulate and recruit antigen-presenting cells to mature and activate T cells, rendering cancer cells more sensitive to ICIs. Importantly, the combination strategy reshapes the tumor immune microenvironment to enhance the antitumor immune response and significantly suppresses the tumor growth and eliminates metastasis. This study offers theoretical guidance for the combination of PDT and ICIs as a potential therapeutic option in lung cancer.

Structural optimization of BODIPY photosensitizers for enhanced photodynamic antibacterial activities.

Enhancing the interactions between photosensitizers and bacteria is key to developing effective photodynamic antibacterial agents. However, the influence of different structures on the therapeutic effects has not been systematically investigated. Herein, 4 BODIPYs with distinct functional groups, including the phenylboronic acid (PBA) group and pyridine (Py) cations, were designed to explore their photodynamic antibacterial activities. The BODIPY with the PBA group (IBDPPe-PBA) exhibits potent activity against planktonic Staphylococcus aureus (S. aureus) upon illumination, while the BODIPY with Py cations (IBDPPy-Ph) or both the PBA group and Py cations (IBDPPy-PBA) can significantly minimize the growth of both S. aureus and Escherichia coli (E. coli). In particular, IBDPPy-Ph can not only eliminate the mature S. aureus biofilm and E. coli biofilm in vitro, but also promote the healing of the infected wound. Our work provides an alternative for reasonable design of photodynamic antibacterial materials.

Structural Engineering of Ionic MOF@COF Heterointerface for Exciton-Boosting Sunlight-Driven Photocatalytic Filter.

Sunlight-driven photocatalytic filters against pathogenic bioaerosols have attracted a lot of interest. However, developing an efficient interception system that shows enhanced visible-light harvesting, controllable charge dynamic, and boosted ROS generation remains a grand challenge. Here, we designed an ionic ZIF-8@iCOF nanocomposite as a sunlight-driven photocatalytic filter through elaborate structural engineering of the heterointerface between ZIF-8 and cationic iCOF layers. The photoactive experiments reveal significant improvements in the visible light absorption and sunlight-driven exciton-enhanced intersystem crossing to boost the generation of singlet oxygen (220%) and also obtain antibacterial efficiency of 99.99999% after 15 min irradiation. After combining with commercial polymer, resultant ZIF-8@iCOF/polyacrylonitrile (PAN) fibrous membranes exhibited high interception efficiency for both PM10 and PM2.5 (98%), being close to the commercial N95. This fibrous membrane also possesses good biocompatibility and strong elimination of bacteria under sunlight conditions, satisfying for the long-lasting contact usage. This finding not only showcases the promise of the porous materials-based fibrous membranes for efficient photocatalytic filter against pathogenic bioaerosols but also highlights the importance of accurate structural engineering for the advancement of sunlight-driven photocatalytic systems in environment and energy-related fields.

Multivariate Strategy Preparation of Nanoscale Ru-Doped Metal-Organic Frameworks with Boosted Photoactivity for Bioimaging and Reactive Oxygen Species Generation.

How to incorporate chromophores into MOFs is a key for the development of multifunctional photoactive systems. The poor internalization by cancer cells and low efficiency of ROS generation hamper the potential clinic application of Ru-based molecular agents. In this work, a nanoscale Ru-doped metal-organic framework Hf-UiO-Ru (Hf-Ru) with framework-boosted photoactivities was prepared via a multivariate strategy for use in bioimaging and ROS generation. The as-synthesized Hf-Ru nanocrystals not only maintain the well regular morphology and crystal structure in comparison with that of the Hf-UiO-66 prototype but also give an oxygen-independent emission with a much longer lifetime, higher quantum yield, and stronger ROS generation than molecular Ru(dcbpy)3. Additionally, the enhanced cellular uptake and high brightness in fluorescence and CT imaging of Hf-Ru nanocrystals have also been well studied in vitro. This multivariate strategy may be utilized as a general paradigm to develop a photoactive nanosystem for bioimaging and cancer treatment.

Multifunctional BODIPY for effective inactivation of Gram-positive bacteria and promotion of wound healing.

Bacterial infectious diseases and antimicrobial resistance seriously endanger human health, so alternative therapies for bacterial infections are urgently needed. Recently, photodynamic therapy against bacteria has shown great potential because of its high efficiency and low acquired resistance. Here, we design and synthesize a dipyrromethene boron difluoride (BODIPY) photosensitizer containing a guanidine group LIBDP for combating bacterial infections. The positively charged guanidine can destroy the bacterial membrane and inhibit the proliferation of bacteria to a certain extent. Upon light irradiation, LIBDP can produce reactive oxygen species (ROS), which can destroy the pre-formed biofilm and induce potent antibacterial activity. In addition, the guanidine of LIBDP can be oxidized to nitric oxide (NO) by the generated ROS, which can not only improve the antibacterial effect, but also promote wound healing. The strategy in this work paves the way for synthesizing high-performance antibacterial materials.

Structural diversity of nanoscale zirconium porphyrin MOFs and their photoactivities and biological performances.

Photoactive MOF-based delivery systems are highly attractive for photodynamic therapy (PDT), but the fundamental interplay among structural parameters and photoactivity and biological properties of these MOFs remains unclear. Herein, porphyrinic MOF isomers (TCPP-MOFs), constructing using the same building blocks into distinct topologies, have been selected as ideal models to understand this problem. Both the intramolecular distances and molecular polarization within TCPP-MOFs isomers collectively contribute to the photoactivity of generating reactive oxygen species. Remarkably, the morphology-determined endocytic pathways and cytotoxicity, as well as good biocompatibility have been confirmed for TCPP-MOF isomers without any chemical modification for the first time. Besides the topology-dependent photoactive regulation, this work also provides in-depth insights into the biological effect from the MOF nanoparticles with controllable structural factors, benefiting further in vivo applications and clinical transformation.

Ionic Covalent-Organic Framework Nanozyme as Effective Cascade Catalyst against Bacterial Wound Infection.

The increasing resistance risks of conventional antibiotic abuse and the formed biofilm on the surface of wounds have been demonstrated to be the main problems for bacteria-caused infections and unsuccessful wound healing. Treatment by reactive oxygen species, such as the commercial H2 O2 , is a feasible way to solve those problems, but limits in its lower efficiency. Herein, an ionic covalent-organic framework-based nanozyme (GFeF) with self-promoting antibacterial effect and good biocompatibility has been developed as glucose-triggered cascade catalyst against bacterial wound infection. Besides the efficient conversion of glucose to hydrogen peroxide, the produced gluconic acid by loading glucose oxidase can supply a compatible catalytic environment to substantially improve the peroxidase activity for generating more toxic hydroxyl radicals. Meanwhile, the adhesion between the positively charged GFeF and the bacterial membrane can greatly enhance the healing effects. This glucose-triggered cascade strategy can reduce the harmful side effects by indirectly producing H2 O2 , potentially used in the wound healing of diabetic patients.

Defect Engineering of Nanoscale Hf-Based Metal-Organic Frameworks for Highly Efficient Iodine Capture.

With the rapid development of the nuclear industry, how to deal with radioactive iodine waste in a timely and effective manner has become an important issue to be solved urgently. Herein, the defect-engineering strategy has been applied to develop a metal-organic framework (MOF)-based solid adsorbent by using the classical UiO-type Hf-UiO-66 as an example. After simple acid treatment, the produced defect-containing Hf-UiO-66 (DHUN) not only retains its topological structure, high crystallization, and regular shape but also shows a great increase in the Brunauer-Emmett-Teller value and pore size in comparison with the original Hf-UiO (HUN). These formed defects within DHUN have been demonstrated to be important for the great enhancement of the iodine capture and following application in computed tomography imaging in vitro. This present work gives a new insight into the control and formation of defect sites, and this simple and efficient defect-engineering strategy also shows great promise for the development of novel solid adsorbents and other functional MOF materials.

Near-infrared-emitting AIE multinuclear cationic Ir(III) complex-assembled nanoparticles for photodynamic therapy.

Near-infrared (NIR) emission and impressive singlet oxygen (1O2) generation ability are highly desirable but remain difficult to realize as aggregation-induced emission (AIE) photosensitizers (PSs). Herein, mono- and tri-nuclear NIR AIE cationic Ir(iii) complexes and their corresponding self-assembled nanoparticles (NPs) without any surfactants or adjuvants were designed and synthesized by integrating rigid 1,3,5-triphenyl benzene as an extended π-conjugation bridge. The pure NPs exhibit multiple merits of stronger NIR emission, higher 1O2 production capacity, better water solubility and negligible dark toxicity compared with the Ir(iii) complexes. Notably, the AIE PS3 NPs possess bright NIR emission at 730 nm, suitable spherical sizes below 100 nm, favorable cellular uptake and superior phototoxicity (IC50 = 1.4 × 10-6 M). These are the first pure NIR-emitting multinuclear Ir(iii) complex NPs obtained by self-assembly that exhibit excellent cell imaging and photodynamic therapy (PDT) performance.

Water-soluble cyclometalated Ir(III) complexes as carrier-free and pure nanoparticle photosensitizers for photodynamic therapy and cell imaging.

Herein, we provide a new and facile strategy to successfully overcome the inherent aggregation-caused quenching effect and hydrophobicity that exist in traditional PSs by the introduction of sodium salts. The obtained water-soluble Ir(iii) complexes as carrier-free and pure nanoparticle photosensitizers exhibit excellent performance in photodynamic therapy and cell imaging.

Endogenous Hydrogen Sulfide-Triggered MOF-Based Nanoenzyme for Synergic Cancer Therapy.

The developing nanoparticle therapeutic agents triggered by tumor microenvironment are a feasible strategy for the substantial elevation of accuracy of diagnosis and the reduction of side effects in cancer treatments. Dysregulated H2S production from the enzyme system of overexpressed cystathionine ß-synthase has long been considered to act as an autocrine and paracrine factor for the tumor growth and proliferation of colon cancer. Herein, for the first time, an endogenous H2S-activated copper metal-organic framework (Cu-MOF; HKUST-1) nanoenzyme has been demonstrated to synergistically mediate H2S-activated near-infrared photothermal therapy and chemodynamic therapy in the effective treatment of colon cancer. This endogenous biomarker-triggered "turn-on" strategy to generate therapeutic agents in situ could largely simplify the constitution of nanomedicine by avoiding the cargo introduction and thus supply great promise for the precise treatments of colon cancer.

Self-quenching synthesis of coordination polymer pre-drug nanoparticles for selective photodynamic therapy.

The design and preparation of a photoactive coordination polymer nanoplatform with tumor-related stimuli-activatability and biodegradability is highly desirable for achieving highly precise photodynamic therapy (PDT). Herein, novel "pre-photodynamic" nanoparticles (Fe-IBDP NPs) with a tumor microenvironment (TME)-activatable PDT and good biodegradability were synthesized by carrying out facile coordination assembly of an IBDP photosensitizer with an Fe3+ quenching agent. After being taken up by cancer cells, our "inactive" Fe-IBDP NPs were activated by the TME and as a result decomposed and released the photoactive carboxyl-functionalized diiodo-substituted BODIPY (IBDP) photosensitizer, which generated cytotoxic singlet oxygen (1O2) under light irradiation. By contrast, these NPs showed relatively low cytotoxicity in normal cells. This work also provided a feasible method for preparing the next generation of photoactive nanomedicines for use in precise phototherapy.

Direct formation of wafer scale graphene thin layers on insulating substrates by chemical vapor deposition.

Direct formation of high-quality and wafer scale graphene thin layers on insulating gate dielectrics such as SiO(2) is emergent for graphene electronics using Si-wafer compatible fabrication. Here, we report that in a chemical vapor deposition process the carbon species dissociated on Cu surfaces not only result in graphene layers on top of the catalytic Cu thin films but also diffuse through Cu grain boundaries to the interface between Cu and underlying dielectrics. Optimization of the process parameters leads to a continuous and large-area graphene thin layers directly formed on top of the dielectrics. The bottom-gated transistor characteristics for the graphene films have shown quite comparable carrier mobility compared to the top-layer graphene. The proposed method allows us to achieve wafer-sized graphene on versatile insulating substrates without the need of graphene transfer.