Bottle Nanomotors Amplify Tumor Oxidative Stress for Enhanced Calcium Overload/Chemodynamic Therapy.

Developing multifunctional, stimuli-responsive nanomedicine is intriguing because it has the potential to effectively treat cancer. Yet, poor tumor penetration of nanodrugs results in limited antitumor efficacy. Herein, an oxygen-driven silicon-based nanomotor (Si-motor) loaded with MnO and CaO2 nanoparticles is developed, which can move in tumor microenvironment (TME) by the cascade reaction of CaO2 and MnO. Under acidic TME, CaO2 reacts with acid to release Ca2+ to induce mitochondrial damage and simultaneously produces O2 and H2O2, when the loaded MnO exerts Fenton-like activity to produce ·OH and O2 based on the produced H2O2. The generated O2 drives Si-motor forward, thus endowing active delivery capability of the formed motors in TME. Meanwhile, MnO with glutathione (GSH) depletion ability further prevents reactive oxygen species (ROS) from being destroyed. Such TME actuated Si-motor with enhanced cellular uptake and deep penetration provides amplification of synergistic oxidative stresscaused by intracellular Ca2 + overloading, GSH depletion induced by Mn2+, and Mn2+ mediated chemodynamic treatment (CDT), leading to excellent tumor cell death. The created nanomotor may offer an effective platform for active synergistic cancer treatment.

Injectable Oxygen-Carrying Microsphere Hydrogel for Dynamic Regulation of Redox Microenvironment of Wounds.

The delayed healing of infected wounds can be attributed to the increased production of reactive oxygen species (ROS) and consequent damages to vascellum and tissue, resulting in a hypoxic wound environment that further exacerbates inflammation. Current clinical treatments including hyperbaric oxygen therapy and antibiotic treatment fail to provide sustained oxygenation and drug-free resistance to infection. To propose a dynamic oxygen regulation strategy, this study develops a composite hydrogel with ROS-scavenging system and oxygen-releasing microspheres in the wound dressing. The hydrogel itself reduces cellular damage by removing ROS derived from immune cells. Simultaneously, the sustained release of oxygen from microspheres improves cell survival and migration in hypoxic environments, promoting angiogenesis and collagen regeneration. The combination of ROS scavenging and oxygenation enables the wound dressing to achieve drug-free anti-infection through activating immune modulation, inhibiting the secretion of pro-inflammatory cytokines interleukin-6, and promoting tissue regeneration in both acute and infected wounds of rat skins. Thus, the composite hydrogel dressing proposed in this work shows great potential for dynamic redox regulation of infected wounds and accelerates wound healing without drugs.

Acridinedione-phthalimide conjugates: Intramolecular electron transfer and singlet oxygen generation studies for optical and photodynamic therapy applications.

We reported herein the synthesis, characterization of hybrid conjugates composed of phthalimide (Phth) and acridine-1,8-diones (Acr) for optical and medical applications. For the synthetic procedure, a three-step synthetic strategy has been utilized. The optical properties of the examined 1,8-acridinedione-phthalimide connected molecules (AcrPhth 1-5) have been examined utilizing various spectroscopic techniques, e.g., steady-state absorption and fluorescence, and time-correlated single photon counting. The steady-state absorption studies showed that AcrPhth 1-5 absorbs the light in the UV and visible region. The fluorescence studies of AcrPhth 1-5 exhibited significant fluorescence quenching compared to the acridinedione control compounds (Acr 1-5) suggesting the occurrence of electron-transfer reactions from the electron donating acridinedione moiety (Acr) to the electron accepting phthalimide moiety (Phth). The rate and efficiency of the electron-transfer reactions were determined from the fluorescence lifetime measurements indicating the fast electron-transfer processes of the covalently connected AcrPhth 1-5 conjugates. Computational studies supported the intramolecular electron-transfer reaction of AcrPhth conjugates using ab initio B3LYP/6-311G methods. In the optimized structures, the HOMO was found to be entirely located on the Acr entity, while the LUMO was found to be entirely on the Phth entity. Further, the synthesized compounds were tested as photosensitizers for generating the singlet oxygen species, which is a key factor in the photodynamic therapy (PDT) applications. The nanosecond laser flash measurements enable us to detect the triplet-excited states of examined Acr and AcrPhth conjugates, determining the triplet quantum yields, and direct detecting the singlet oxygen in an accurate way. From this observation, the singlet quantum yields were found to be in the range of 0.12-0.27 (for Acr 1-5) and 0.07-0.19 (for AcrPhth 1-5 conjugates). The molecular docking studies revealed that compound AcrPhth 2 exhibited high binding affinity with for key genes (p53, TOP2B, p38, and EGFR) suggesting its potential as a targeted anticancer therapy.

Mild selective photochemical oxidation of an organic sulfide using OxP-polyimide porous polymers as singlet oxygen generators.

A series of porous organic polymers based on a singlet oxygen generating oxoporphyinogen ('OxP') has been successfully prepared from a pseudotetrahedral OxP-tetraamine precursor (OxP(4-NH2Bn)4) by its reaction with tetracarboxylic acid dianhydrides under suitable conditions. Of the compounds studied, those containing naphthalene (OxP-N) and perylene (OxP-P) spacers, respectively, have large surface areas (~530 m2 g-1). On the other hand, the derivative with a simple benzene spacer (OxP-B) exhibits the best 1O2 generating capability. Although the starting OxP-tetraamine precursor is a poor 1O2 generator, its incorporation into OxP POPs leads to a significant enhancement of 1O2 productivity, which is largely due to the transformation of NH2 groups to electron-withdrawing diimides. Overall 1O2 production efficacy of OxP-POPs under irradiation by visible light is significantly improved over the common reference material PCN-222. All the materials OxP-B, OxP-N and OxP-P promote oxidation of thioanisole involving conversion of ambient triplet state oxygen to singlet oxygen under visible light irradiation and its reaction with the sulfide. Although the reaction rate of the oxidation promoted by OxP POPs is generally lower than for conventional materials (such as PCN-222) or previously studied OxP derivatives, undesired overoxidation of the substrate to methyl phenyl sulfone is suppressed. For organic sulfides, selectivity of oxidation is especially important for detoxification of mustard gas (bis(2-chloroethyl)sulfide) or similarly toxic compounds since controlled oxidation leads to the low toxicity bis(2-chloroethyl)sulfoxide while overoxidation leads to intoxification (since bis(2-chloroethyl)sulfone presents greater toxicity to humans than the sulfide substrate). Therefore, OxP POPs capable of promoting selective oxidation of sulfides to sulfoxides have excellent potential to be used as mild and selective detoxification agents.

Oxoporphyrinogen (OxP) is a unique chromophore compound in that it is intrinsically de-aggregated allowing large quantum yields of singlet oxygen generation. Due to its structure, OxP is also an ideal building block for porous systems. In this work, we describe the first incorporation of OxP in highly stable microporous polymers strongly enhanced singlet oxygen generation for selective oxidation of organic sulfides to sulfoxides (as a model reaction) under heterogeneous conditions. The novelty of this work lies in the high stability and easy recovery of the materials, the synergetic enhancement of singlet oxygen generation in the polymers over the starting OxP, and the excellent selectivity for the oxidation reaction.

Dual and Sequential Locked/Unlocked Photochromic Effects on FRET Controlled Singlet Oxygen Processes by Contracted/Extended Forms of Diarylethene-Based [1]Rotaxane Nanoparticles.

Manipulations of singlet oxygen (1 O2 ) generations by the integration of both aggregation-induced emission luminogen (AIEgen) photosensitizer and photochromic moieties have diversified features in photodynamic therapy applications. Through Förster resonance energy transfer (FRET) pathway to induce red PL emissions (at 595 nm) for 1 O2 productions, [1]rotaxane containing photosensitive tetraphenylethylene (TPE) donor and photochromic diarylethene (DAE) acceptor is introduced to achieve dual and sequential locked/unlocked photoswitching effects by pH-controlled shuttling of its contracted/extended forms. Interestingly, the UV-enabled DAE ring closure speeds follow the reversed trend of DAE self-constraint degree as: contracted < extended < noninterlocked forms in [1]rotaxane analogues, thus FRET processes can be adjusted in contracted/extended forms of [1]rotaxane upon UV irradiations. Accordingly, the contracted form of [1]rotaxane is FRET-OFF locked and inert to UV exposure due to the larger bending conformation of DAE parallel (p-)conformer, compared with its extended and noninterlocked analogues possessing switchable FRET-OFF/ON behaviors activated by dual and sequential pH- and photoswitching. Owing to the advantages of 1 O2 productions tuned by multistimuli inputs (pH, UV, and blue light), an useful logic circuit for toxicity outputs of the surface modified [1]rotaxane nanoparticles (NPs) has been demonstrated to offer promising 1 O2 productions and managements based on mechanically interlocked molecules for future bioapplications.

Manganese-Based Immunomodulatory Nanocomposite with Catalase-Like Activity and Microwave-Enhanced ROS Elimination Ability for Efficient Rheumatoid Arthritis Therapy.

Rheumatoid arthritis (RA) is a chronic autoimmune disease commonly associated with the accumulation of hyperactive immune cells (HICs), particularly macrophages of pro-inflammatory (M1) phenotype, accompanied by the elevated level of reactive oxygen species (ROS), decreased pH and O2 content in joint synovium. In this work, an immunomodulatory nanosystem (IMN) is developed for RA therapy by modulating and restoring the function of HICs in inflamed tissues. Manganese tetraoxide nanoparticles (Mn3 O4 ) nanoparticles anchored on UiO-66-NH2 are designed, and then the hybrid is coated with Mn-EGCG film, further wrapped with HA to obtain the final nanocomposite of UiO-66-NH2 @Mn3 O4 /Mn-EGCG@HA (termed as UMnEH). When UMnEH diffuses to the inflammatory site of RA synovium, the stimulation of microwave (MW) irradiation and low pH trigger the slow dissociation of Mn-EGCG film. Then the endogenously overexpressed hydrogen peroxide (H2 O2 ) disintegrates the exposed Mn3 O4 NPs to promote ROS scavenging and O2 generation. Assisted by MW irradiation, the elevated O2 content in the RA microenvironment down-regulates the expression of hypoxia-inducible factor-1α (HIF-1α). Coupled with the clearance of ROS, it promotes the re-polarization of M1 phenotype macrophages into anti-inflammatory (M2) phenotype macrophages. Therefore, the multifunctional UMnEH nanoplatform, as the IMN, exhibits a promising potential to modulate and restore the function of HICs and has an exciting prospect in the treatment of RA.

Structural Switching of a Distorted Trigonal Metal-Organic Cage to a Tetragonal Cage and Singlet Oxygen Mediated Oxidations.

Construction of metal-organic cages with unique architecture and guest binding abilities is highly desirable. Herein, we report the synthesis of a distorted trigonal cage (1) from a twisted tetratopic ligand (L) and a PdII acceptor. Surprisingly, 1 exhibited a complete structural reorganization of its building units in the presence of C70 and C60 to form guest-encapsulated tetragonal cages, (C70 )2 @2 and (C60 )2 @2, respectively. These guest-bound cages were found to be potential 1 O2 generators, with the former effectively catalyzing two different varieties of 1 O2 -mediated oxidation reactions.

Characterization of a Novel Amphiphilic Cationic Chlorin Photosensitizer for Photodynamic Applications.

A novel amphiphilic cationic chlorin e6 derivative was investigated as a promising photosensitizer for photodynamic therapy. Two cationic -N(CH3)3+ groups on the periphery of the macrocycle provide additional hydrophilization of the molecule and ensure its electrostatic binding to the mitochondrial membranes and bacterial cell walls. The presence of a hydrophobic phytol residue in the same molecule results in its increased affinity towards the phospholipid membranes while decreasing its stability towards aggregation in aqueous media. In organic media, this chlorin e6 derivative is characterized by a singlet oxygen quantum yield of 55%. Solubilization studies in different polymer- and surfactant-based supramolecular systems revealed the effective stabilization of this compound in a photoactive monomolecular form in micellar nonionic surfactant solutions, including Tween-80 and Cremophor EL. A novel cationic chlorin e6 derivative also demonstrates effective binding towards serum albumin, which enhances its bioavailability and promotes effective accumulation within the target tissues. Laser confocal scanning microscopy demonstrates the rapid intracellular accumulation and distribution of this compound throughout the cells. Together with low dark toxicity and a rather good photostability, this compound demonstrates significant phototoxicity against HeLa cells causing cellular damage most likely through reactive oxygen species generation. These results demonstrate a high potential of this derivative for application in photodynamic therapy.

Solvation, Cancer Cell Photoinactivation and the Interaction of Chlorin Photosensitizers with a Potential Passive Carrier Non-Ionic Surfactant Tween 80.

Cancer and drug-resistant superinfections are common and serious problems afflicting millions worldwide. Photodynamic therapy (PDT) is a successful and clinically approved modality used for the management of many neoplastic and nonmalignant diseases. The combination of the light-activated molecules, so-called photosensitizers (PSs), with an appropriate carrier, is proved to enhance PDT efficacy both in vitro and in vivo. In this paper, we focus on the solvation of several potential chlorin PSs in the 1-octanol/phosphate saline buffer biphasic system, their interaction with non-ionic surfactant Tween 80 and photoinactivation of cancer cells. The chlorin conjugates containing d-galactose and l-arginine fragments are found to have a much stronger affinity towards a lipid-like environment compared to ionic chlorins and form molecular complexes with Tween 80 micelles in water with two modes of binding. The charged macrocyclic PSs are located in the periphery of surfactant micelles near hydrophilic head groups, whereas the d-galactose and l-arginine conjugates are deeper incorporated into the micelle structure occupying positions around the first carbon atoms of the hydrophobic surfactant residue. Our results indicate that both PSs have a pronounced affinity toward the lipid-like environment, leading to their preferential binding to low-density lipoproteins. This and the conjugation of chlorin e6 with the tumor-targeting molecules are found to enhance their accumulation in cancer cells and PDT efficacy.

Preliminary Studies of Antimicrobial Activity of New Synthesized Hybrids of 2-Thiohydantoin and 2-Quinolone Derivatives Activated with Blue Light.

Thiohydantoin and quinolone derivatives have attracted researchers' attention because of a broad spectrum of their medical applications. The aim of our research was to synthesize and analyze the antimicrobial properties of novel 2-thiohydantoin and 2-quinolone derivatives. For this purpose, two series of hybrid compounds were synthesized. Both series consisted of 2-thiohydantoin core and 2-quinolone derivative ring, however one of them was enriched with an acetic acid group at N3 atom in 2-thiohydantoin core. Antibacterial properties of these compounds were examined against bacteria: Staphylococcus aureus, Bacillus subtilis, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. The antimicrobial assay was carried out using a serial dilution method to obtain the MIC. The influence of blue light irradiation on the tested compounds was investigated. The relative yield of singlet oxygen (1O2*, 1Δg) generation upon excitation with 420 nm was determined by a comparative method, employing perinaphthenone (PN) as a standard. Antimicrobial properties were also investigated after blue light irradiation of the suspensions of the hybrids and bacteria placed in microtitrate plates. Preliminary results confirmed that some of the hybrid compounds showed bacteriostatic activity to the reference Gram-positive bacterial strains and a few of them were bacteriostatic towards Gram-negative bacteria, as well. Blue light activation enhanced bacteriostatic effect of the tested compounds.

Metal Coordination Effects on the Photophysics of Dipyrrinato Photosensitizers.

Within this work, we review the metal coordination effect on the photophysics of metal dipyrrinato complexes. Dipyrrinato complexes are promising candidates in the search for alternative transition metal photosensitizers for application in photodynamic therapy (PDT). These complexes can be activated by irradiation with light of a specific wavelength, after which, cytotoxic reactive oxygen species (ROS) are generated. The metal coordination allows for the use of the heavy atom effect, which can enhance the triplet generation necessary for generation of ROS. Additionally, the flexibility of these complexes for metal ions, substitutions and ligands allows the possibility to tune their photophysical properties. A general overview of the mechanism of photodynamic therapy and the properties of the triplet photosensitizers is given, followed by further details of dipyrrinato complexes described in the literature that show relevance as photosensitizers for PDT. In particular, the photophysical properties of Re(I), Ru(II), Rh(III), Ir(III), Zn(II), Pd(II), Pt(II), Ni(II), Cu(II), Ga(III), In(III) and Al(III) dipyrrinato complexes are discussed. The potential for future development in the field of (dipyrrinato)metal complexes is addressed, and several new research topics are suggested throughout this work. We propose that significant advances could be made for heteroleptic bis(dipyrrinato)zinc(II) and homoleptic bis(dipyrrinato)palladium(II) complexes and their application as photosensitizers for PDT.

Inspired oxygen: present, past, and future.

As earthlings, we take the oxygen in the air that we breathe for granted. Few people realize that this easy access to oxygen makes us unique in the whole universe. Nowhere else in our planetary system or in distant stars has stable oxygen ever been detected. However, the present plentiful supply of oxygen in our atmosphere was not always there. Long after the Earth was formed some 4.5 billion years ago, the Po2 in the atmosphere was near zero, and it remained so for millions of years. But about 2 billion years ago, the Po2 dramatically increased to as high as 200 mmHg during the Great Oxygen Event, due to the activity of microorganisms, the cyanobacteria. Subsequently, the oxygen level fell to the intermediate values that we have today. Here, we also look to the future, for example, the next 50 years. This period will be special because it will include the beginnings of human space exploration, initially to the Moon and Mars. Neither of these has atmospheric oxygen. Nevertheless, plans to visit and live on both of these are developing rapidly. We consider the fascinating problems of how to ensure that sufficient oxygen will be available for the groups of people. Although it is interesting to discuss these issues now, we can expect that major advances will be made in the next few years.

Self-Oxygenation of Tissues Orchestrates Full-Thickness Vascularization of Living Implants.

Bioengineering of tissues and organs has the potential to generate functional replacement organs. However, achieving the full-thickness vascularization that is required for long-term survival of living implants has remained a grand challenge, especially for clinically sized implants. During the pre-vascular phase, implanted engineered tissues are forced to metabolically rely on the diffusion of nutrients from adjacent host-tissue, which for larger living implants results in anoxia, cell death, and ultimately implant failure. Here it is reported that this challenge can be addressed by engineering self-oxygenating tissues, which is achieved via the incorporation of hydrophobic oxygen-generating micromaterials into engineered tissues. Self-oxygenation of tissues transforms anoxic stresses into hypoxic stimulation in a homogenous and tissue size-independent manner. The in situ elevation of oxygen tension enables the sustained production of high quantities of angiogenic factors by implanted cells, which are offered a metabolically protected pro-angiogenic microenvironment. Numerical simulations predict that self-oxygenation of living tissues will effectively orchestrate rapid full-thickness vascularization of implanted tissues, which is empirically confirmed via in vivo experimentation. Self-oxygenation of tissues thus represents a novel, effective, and widely applicable strategy to enable the vascularization living implants, which is expected to advance organ transplantation and regenerative medicine applications.

Effect of Topology on Photodynamic Sterilization of Porphyrinic Metal-Organic Frameworks.

Porphyrinic metal-organic frameworks (MOFs) are promising photosensitizers due to the lack of self-aggregation of porphyrin in aqueous solution. However, how the topology of porphyrinic MOFs affects the generation of singlet oxygen (1 O2 ) is unclear. Here, the effect of the topology of porphyrinic MOFs on their photodynamic performance is reported. Four porphyrinic zirconium MOFs (MOF-525, MOF-545, PCN-223 and PCN-224 with different topologies: ftw, csq, shp and she, respectively) were selected to study the influence of topology on the photodynamic antibacterial performance. The 1 O2 generation and the photodynamic antibacterial performance followed an decreasing order of MOF-545>MOF-525>PCN-224>PCN-223. The results reveal that the pore size, the distance between porphyrin, and the number of porphyrin per Zr6 O8 cluster in MOFs greatly affected 1 O2 generation. This work provides guidance for designing new MOFs for efficient photodynamic sterilization.

Supramolecular Control of Singlet Oxygen Generation.

Singlet oxygen (1O2) is the excited state electronic isomer and a reactive form of molecular oxygen, which is most efficiently produced through the photosensitized excitation of ambient triplet oxygen. Photochemical singlet oxygen generation (SOG) has received tremendous attention historically, both for its practical application as well as for the fundamental aspects of its reactivity. Applications of singlet oxygen in medicine, wastewater treatment, microbial disinfection, and synthetic chemistry are the direct results of active past research into this reaction. Such advancements were achieved through design factors focused predominantly on the photosensitizer (PS), whose photoactivity is relegated to self-regulated structure and energetics in ground and excited states. However, the relatively new supramolecular approach of dictating molecular structure through non-bonding interactions has allowed photochemists to render otherwise inactive or less effective PSs as efficient 1O2 generators. This concise and first of its kind review aims to compile progress in SOG research achieved through supramolecular photochemistry in an effort to serve as a reference for future research in this direction. The aim of this review is to highlight the value in the supramolecular photochemistry approach to tapping the unexploited technological potential within this historic reaction.

Determination and analysis of singlet oxygen quantum yields of talaporfin sodium, protoporphyrin IX, and lipidated protoporphyrin IX using near-infrared luminescence spectroscopy.

In photodynamic therapy (PDT), singlet oxygen ([Formula: see text]) is the main species responsible for promoting tumor cell death. The determination of the quantum yield (ΦΔ) of a photosensitizer (PS) is important for dosimetry. The purpose of this paper is to quantify the [Formula: see text] generated by the PS by near-infrared spectroscopy (NIRS). The ΦΔ of different PS species were measured by the detection of near-infrared [Formula: see text] luminescence. From the measurement results, the ΦΔ of talaporfin sodium, protoporphyrin IX (PpIX), and lipidated PpIX (PpIX lipid) were measured as 0.53, 0.77, and 0.87, respectively. In addition, the ΦΔ values of PpIX in a hypoxic and oxic solution were evaluated, since tumors are associated with regions of hypoxia. The measured ΦΔ indicated a same value at high (DO: 20%) and low (DO: 1%) oxygen concentrations. Using the measured ΦΔ, the amount of [Formula: see text] generated by the PSs was estimated using [[Formula: see text]] = D*ΦΔ, where D* is the total excited PS concentration. The generated [Formula: see text] amounts were little different at the high and the low oxygen concentrations, and the generated [Formula: see text] amount for each PS was different depending on each ΦΔ. The NIRS measurement determined the ΦΔ of talaporfin sodium, PpIX, and PpIX lipid. The quantitative evaluation based on the measured ΦΔ will support the development of PDT treatment monitoring and design.

Photosensitizing potential of tailored magnetite hybrid nanoparticles functionalized with levan and zinc (II) phthalocyanine.

Phototherapies, including photodynamic therapy (PDT), have been widely used in the treatment of various diseases, especially for cancer. However, there is still a lack of effective, safe photosensitizers that would be well tolerated by patients. The combination of several methods (like phototherapy and hyperthermia) constitutes a modern therapeutic approach, which demands new materials based on components that are non-toxic without irradiation. Therefore, this study presents the synthesis and properties of novel, advanced nanomaterials in which the advantage features of the magnetic nanoparticles and photoactive compounds were combined. The primary purpose of this work was the synthesis of magnetic nanoparticles coated with biocompatible and antitumor polysaccharide - levan, previously unknown from scientific literature, and the deposition of potent photosensitizer - zinc(II) phthalocyanine on their surface. In order to better characterize the nature of the coating covering the magnetic core, the atomic force microscope analysis, a contact angle measurement, and the mechanical properties of pure levan and its blend with zinc(II) phthalocyanine films were investigated. This magnetic nanomaterial revealed the ability to generate singlet oxygen upon exposure to light. Finally, preliminary toxicity of obtained nanoparticles was tested using the Microtox® test - with and without irradiation.

Biomimetic Hybrid Nanozymes with Self-Supplied H+ and Accelerated O2 Generation for Enhanced Starvation and Photodynamic Therapy against Hypoxic Tumors.

Nanozymes as artificial enzymes that mimicked natural enzyme-like activities have received great attention in cancer diagnosis and therapy. Biomimetic nanozymes require more consideration regarding complicated tumor microenvironments to mimic biological enzymes, thus achieving superior nanozyme activity in vivo. Here we report a biomimetic hybrid nanozyme (named rMGB) which integrates natural enzyme glucose oxidase (GOx) with nanozyme manganese dioxide (MnO2) by mutual promotion for maximizing the enzymatic activity of MnO2 and GOx. Under hypoxia environment, we observed that MnO2 could react with endogenous H2O2 to produce O2 for enhancing the catalytic efficiency of GOx for starvation therapy. Meanwhile, we confirmed that glucose oxidation generated gluconic acid and further improved the catalytic efficiency of MnO2 subsequently. The biochemical reaction cycle, consisting of MnO2, O2, GOx, and H+, was triggered by the tumor microenvironment and accelerated each other so as to achieve self-supplied H+ and accelerate O2 generation, enhancing the starvation therapy, alleviating tumor hypoxia and accelerating the reactive oxygen species generation in photodynamic therapy. This biomimetic hybrid nanozyme would further facilitate the development of biological nanozymes for cancer treatment.

MOF-Derived Double-Layer Hollow Nanoparticles with Oxygen Generation Ability for Multimodal Imaging-Guided Sonodynamic Therapy.

The high reactive oxygen species (ROS) generation ability and simple construction of sonosensitizer systems remain challenging in sonodynamic therapy against the hypoxic tumor. In this work, we rationally prepared MOF-derived double-layer hollow manganese silicate nanoparticle (DHMS) with highly effective ROS yield under ultrasound irradiation for multimodal imaging-guided sonodynamic therapy (SDT). The presence of Mn in DHMS increased ROS generation efficiency because it could be oxidized by holes to improve the electron-hole separation. Moreover, DHMS could produce oxygen in the tumor microenvironment, which helps overcome the hypoxia of the solid tumor and thus enhance the treatment efficiency. In vivo experiments demonstrated efficient tumor inhibition in DHMS-mediated SDT guided by ultrasound and magnetic resonance imaging. This work presents a MOF-derived nanoparticle with sonosensitive and oxygen generating ability, which provides a promising strategy for tumor hypoxia in SDT.

In-Situ Oxygen-Evolving Photoactive Nanococktail: The Future of Hypoxic Tumour Photodynamic Therapy.

Hypoxia-related resistance is one of the main challenges for photodynamic therapy to overcome. This highlight discusses a few current works on possible ways to overcome this problem by in situ oxygen generation in the hypoxic core of tumours.