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Tumor-targeted delivery of nanomedicine is of great importance to improve therapeutic efficacy of cancer and minimize systemic side effects. Unfortunately, nowadays the targeting efficiency of nanomedicine toward tumor is still quite limited and far from clinical requirements. In this work, we develop an innovative peptide-based nanoparticle to realize light-triggered nitric oxide (NO) release and structural transformation for enhanced intratumoral retention and simultaneously sensitizing photodynamic therapy (PDT). The designed nanoparticle is self-assembled from a chimeric peptide monomer, TPP-RRRKLVFFK-Ce6, which contains a photosensitive moiety (chlorin e6, Ce6), a β-sheet-forming peptide domain (Lys-Leu-Val-Phe-Phe, KLVFF), an oligoarginine domain (RRR) as NO donor and a triphenylphosphonium (TPP) moiety for targeting mitochondria. When irradiated by light, the constructed nanoparticles undergo rapid structural transformation from nanosphere to nanorod, enabling to achieve a significantly higher intratumoral accumulation by 3.26 times compared to that without light irradiation. More importantly, the conversion of generated NO and reactive oxygen species (ROS) in a light-responsive way to peroxynitrite anions (ONOO−) with higher cytotoxicity enables NO to sensitize PDT in cancer treatment. Both in vitro and in vivo studies demonstrate that NO sensitized PDT based on the well-designed transformable nanoparticles enables to eradicate tumors efficiently. The light-triggered transformable nanoplatform developed in this work provides a new strategy for enhanced intratumoral retention and improved therapeutic outcome., Graphical abstract Image 1, Highlights • An innovative mitochondria-targeting chimeric peptide composed of four discrete functional domains is designed and prepared. • The peptide can self-assemble into nanospheres and transform into nanorods via light-triggered ROS generation and NO release. • The sphere−to−rod structural transformation remarkably enhances the intratumoral retention and accumulation of nanomedicine. • The conversion of generated ROS and NO to RNS with higher cytotoxicity enables NO to sensitize PDT in cancer treatment.

It is a great challenge to effectively eradicate biofilm and cure biofilm-infected diseases because dense extracellular polymeric substance matrix prevents routine antibacterial agents from penetrating into biofilm. H2 is an emerging energy-regulating molecule possessing both high biosafety and high tissue permeability. In this work, we propose a concept of sonocatalytic hydrogen/hole-combined ‘inside/outside-cooperation’ anti-biofilm for promoting bacteria-infected diabetic wound healing based on two-dimensional piezoelectric nanomaterials. Proof-of-concept experiments using C3N4 nanosheets as a representative piezoelectric catalyst with wide band gap and high biosafety have verified that sonocatalytically generated H2 and holes rapidly penetrate into biofilm to inhibit bacterial energy metabolism and oxidatively deprive polysaccharides/NADH in biofilm to destroy the bacterial membrane/electron transport chain, respectively, inside/outside-cooperatively eradicating biofilm. A bacteria-infected diabetic wound model is used to confirm the excellent in vivo antibacterial performance of sonocatalytic hydrogen/hole-combined therapy, remarkably improving bacteria-infected diabetic wound healing. The proposed strategy of sonocatalytic hole/hydrogen-combined ‘inside/outside-cooperation’ will make a highway for treatment of deep-seated biofilm infection.

Unexpected temporal and spatial extension of inflammation in severely burned patients frequently causes cellular apoptosis, wound deepening, and serious fibroplasia, leading to the difficulty of wound healing and the formation of hypertrophic scar. Molecular hydrogen holds a high potential for wound healing owing to its anti-inflammatory effect and high biosafety, but commonly used hydrogen administration routes hardly achieve the sustained supply of high-dosage hydrogen, limiting hydrogen therapy efficacy. Here, a new type of two-dimensional metal silicide (MSene), Mg

The development of multifunctional theranostic nano-agents is an important resolution for personalized treatment of cancer. In this work, we synthesized a new kind of gadolinium boride nanoparticles (GBN) by a microwave-assisted chemical etching method, and discovered their optical characteristics including fluorescence imaging and near-infrared (NIR) photothermal conversion capability. Bright greenishyellow fluorescence enabled for intracellular localization, while effective NIR-photothermal conversion supported photothermal therapy (PTT). In vitro and in vivo results indicated that GBN exhibited a superior antitumor performance and high biocompatibility. This study demonstrated a promising multifunctional theranostic nanoplatform for cancer treatment.

Synovial microenvironment (SME) plays a vital role in the formation of synovial pannus and the induction of cartilage destruction in arthritis. In this work, a concept of the photocatalytic regulation of SME is proposed for arthritis treatment, and monodispersive hydrogen–doped titanium dioxide nanorods with a rutile single-crystal structure are developed by a full-solution method to achieve near infrared–photocatalytic generation of hydrogen molecules and simultaneous depletion of overexpressed lactic acid (LA) for realizing SME regulation in a collagen-induced mouse model of rheumatoid arthritis. Mechanistically, locally generated hydrogen molecules scavenge overexpressed reactive oxygen species to mediate the anti-inflammatory polarization of macrophages, while the simultaneous photocatalytic depletion of overexpressed LA inhibits the inflammatory/invasive phenotypes of synoviocytes and macrophages and ameliorates the abnormal proliferation of synoviocytes, thereby remarkably preventing the synovial pannus formation and cartilage destruction. The proposed catalysis-mediated SME regulation strategy will open a window to realize facile and efficient arthritis treatment.

Background: Rapid advance in biomedicine has recently vitalized the development of multifunctional two-dimensional (2D) nanomaterials for cancer theranostics. However, it is still challenging to develop new strategy to produce new types of 2D nanomaterials with flexible structure and function for enhanced disease theranostics. Method: We explore the monolayer Bi-anchored manganese boride nanosheets (MBBN) as a new type of MBene (metal boride), and discover their unique near infrared (NIR)-photothermal and photoacoustic effects, X-ray absorption and MRI imaging properties, and develop them as a new nanotheranostic agent for multimodal imaging-guided photothermal therapy of cancer. A microwave-assisted chemical etching route was utilized to exfoliate the manganese boride bulk into the nanosheets-constructed flower-like manganese boride nanoparticle (MBN), and a coordination-induced exfoliation strategy was further developed to separate the MBN into the dispersive monolayer MBBN by the coordination between Bi and B on the surface, and the B-OH group on the surface of MBBN enabled facile surface modification with hyaluronic acid (HA) by the borate esterification reaction in favor of enhanced monodispersion and active tumor targeting. Result: The constructed MBBN displays superior NIR-photothermal conversion efficiency (η=59.4%) as well as high photothermal stability, and possesses versatile imaging functionality including photoacoustic, photothermal, CT and T1 -wighted MRI imagings. In vitro and in vivo evaluations indicate that MBBN had high photothermal ablation and multimodal imaging performances, realizing high efficacy of imaging-guided cancer therapy. Conclusion: We have proposed new MBene concept and exfloliation strategy to impart the integration of structural modification and functional enhancement for cancer theranostics, which would open an avenue to facile fabrication and extended application of multifunctional 2D nanomaterials.

To reveal the biomedical effects and mechanisms of hydrogen molecules urgently needs hydrogen molecular imaging probes as an imperative tool, but the development of these probes is extremely challenging. A catalytic hydrogenation strategy is proposed to design and synthesize a ratiometric fluorescent probe by encapsulating Pd nanoparticles and conjugating azido-/coumarin-modified fluorophore into mesoporous silica nanoparticles, realizing in vitro and in vivo fluorescence imaging of hydrogen molecules. The developed hydrogen probe exhibits high sensitivity, rapid responsivity, high selectivity and low detection limit, enabling rapid and real-time detection of hydrogen molecules both in cells and in the body of animal and plant. By application of the developed fluorescent probe, we have directly observed the super-high transmembrane and ultrafast transport abilities of hydrogen molecules in cells, animals and plants, and discovered in vivo high diffusion of hydrogen molecules.

The development of stimuli-responsively degradable porous carriers for both controlled drug release and high biosafety is vitally important to their clinical translation, but still challenging at present. A new type of porphyrin-iron metal organic framework (Fe-MOF) nanocrystals is engineered here as acid-degradable drug carrier and hydrogen donor by the coordination between porphyrin and zero-valence Fe atom. Fe-MOF nanocrystals exhibit excellent acid-responsive degradation for H

Engineering biomaterials to meet specific biomedical applications raises high requirements of mechanical performances, and simultaneous strengthening and toughening of polymer are frequently necessary but very challenging in many cases. In this work, we propose a new concept of nanoconcrete welding polymer chains, where mesoporous CaCO

A multifunctional CO/thermo/chemotherapy nanoplatform is here reported, which is composed of mesoporous carbon nanoparticles (MCN) as near infrared (NIR)-responsive drug carrier, doxorubicin (DOX) as chemotherapeutic drug and triiron dodecacarbonyl (FeCO) as thermosensitive CO prodrug. The nanoplatform could absorb near-infrared (NIR) light and convert it into ample heat to trigger CO release and could also release DOX in the acidic tumor microenvironment. More importantly, the generated CO molecules successfully increase cancer cell sensitivity to chemotherapeutics by the ferroptosis pathway. Subsequently, under the guidance of photoacoustic imaging, the FeCO-DOX@MCN nanoplatform demonstrates high treatment efficacies in vitro and in vivo by combination of chemotherapy, photothermal therapy and gas therapy. This multifunctional platform with excellent antitumor efficacy has great potential in precision cancer therapy.

Oxidative stress-induced mitochondrial dysfunction plays an important role in the pathogenesis of Alzheimer's disease (AD). Hydrogen molecule, a special antioxidant, can selectively scavenge highly cytotoxic reactive oxygen species such as ·OH, exhibiting a potential to treat AD by reducing oxidative stress. However, there is no effective route to realize the continuous and efficient accumulation of administrated hydrogen in AD brain owing to its low solubility. Here, we develop the small-sized Pd hydride (PdH) nanoparticles for high payload of hydrogen and in situ sustained hydrogen release in AD brain. By virtue of the catalytic hydrogenation effect of Pd, the released hydrogen from PdH nanoparticles exhibits high bio-reductivity in favor of effectively scavenging cytotoxic ·OH in a self-catalysis way. Bio-reductive hydrogen is able to recover mitochondrial dysfunction, inhibit Aβ generation and aggregation, block synaptic and neuronal apoptosis and promote neuronal energy metabolism by eliminating oxidative stress and activating the anti-oxidative pathway, consequently ameliorating the cognitive impairment in AD mice. The proposed hydrogen-releasing nanomedicine strategy would open a new window for the treatment of AD.

Hydrogen therapy is an emerging and promising strategy for treatment of inflammation-related diseases owing to the excellent bio-safety of hydrogen molecules (H 2 ), but is facing a challenge that the H 2 concentration at the local disease site is hardly accumulated because of its high diffusibility and low solubility, limiting the efficacy of hydrogen therapy. Herein, we propose a nanomedicine strategy of imaging-guided tumour-targeted delivery and tumour microenvironment-triggered release of H 2 to address this issue, and develop a kind of biocompatible carboxymethyl cellulose (CMC)-coated/stabilized Fe (Fe@CMC) nanoparticle with photoacoustic imaging (PAI), tumour targeting and acid responsive hydrogen release properties for cancer therapy. The Fe@CMC nanoparticles have demonstrated high intratumoural accumulation capability, high acid responsiveness, excellent PAI performance, selective cancer-killing effect and high bio-safety in vitro and in vivo. Effective inhibition of tumour growth is achieved by intravenous injection of the Fe@CMC nanoparticles, and the selective anti-cancer mechanism of Fe@CMC is discovered to be originated from the energy metabolism homeostasis regulatory function of the released H 2 . The proposed nanomedicine-mediated hydrogen therapy strategy will open a new window for precise, high-efficacy and safe cancer treatment.

Hydrogen gas, which is an important energy resource, was recently discovered to have high advantage in the treatment of many diseases, but the current constraint is the low efficacy of stable hydrogen storage and delivery. By the virtue of the strong hydrogen bonding and catalytic hydrogenation capacity of Pd, we developed a nanoscale porphyrin–palladium metal–organic framework (Pd-MOF) with highly dispersed Pd atoms as hydrogen carriers to efficiently load highly reductive hydrogen for the tumor-targeted photoacoustic imaging (PAI)-guided hydrogenothermal therapy of cancer. The hydrogenated Pd-MOF (PdH-MOF) exhibited a high hydrogen loading capacity, sustained hydrogen release profile, high tumor targeting ability, high photothermal effect and excellent PAI performance. Utilizing these unique advantages of PdH-MOF nanoparticles, high-efficacy hydrogenothermal therapy was achieved by tumor-targeted delivery, PAI-guided therapy, and the sustained release of high payload of highly reductive hydrogen. This study proposes a new strategy for hydrogen storage, activation, delivery and combined therapy using MOFs as a versatile platform.

Drug therapy unavoidably brings toxic side effects and drug content-limited therapeutic efficacy although many nanocarriers have been developed to improve them to a certain extent. In this work, a concept of drug-free therapeutics is proposed and defined as a therapeutic methodology without the use of traditional toxic drugs, without the consumption of therapeutic agents during treatment but with the inexhaustible therapeutic capability to maximize the benefit of treatment, and a Z-scheme SnS1.68-WO2.41 nanocatalyst is developed to achieve near infrared (NIR)-photocatalytic generation of oxidative holes and hydrogen molecules for realizing combined hole/hydrogen therapy by the drug-free therapeutic strategy. Without the need of any drug and other therapeutic agent assistance, the nanocatalyst oxidizes/consumes intratumoral over-expressed glutathione (GSH) by holes and simultaneously generates hydrogen molecules in a lasting and controllable way under NIR irradiation. Mechanistically, generated hydrogen molecules and GSH consumption inhibit cancer cell energy and destroy intratumoral redox balance, respectively, to synergistically damage DNA and induce tumor cell apoptosis. High efficacy and biosafety of combined hole/hydrogen therapy of tumors are achieved by the nanocatalyst. The proposed catalysis-based drug-free therapeutic strategy breaks a pathway to realize high efficacy and low toxicity of cancer treatment., Nanoparticles have been used to reduce the toxicity associated with chemotherapeutic agents. Here, the authors report a Z-scheme SnS1.68-WO2.41 nanocatalyst for photocatalytic generation of oxidative holes and hydrogen molecules for drug-free therapeutic strategy.

Tumor-targeted drug delivery by nanomaterials is important to improve tumor therapy efficacy and reduce toxic side effects, but its efficiency is quite limited. In this work, a new type of MBene, zirconium boride nanosheet (ZBN), as a versatile nanoplatform to realize near-infrared (NIR)-controlled intratumoral retention and drug release is developed. ZBN exhibits high NIR-photothermal conversion efficiency (76.8%), surface modification with hyaluronic acid (HA) by polyol-borate esterfication endows ZBN-HA with good dispersion, and the photopyrolysis of borate ester causes HA detachment and ZBN aggregation, enabling NIR-controlled intratumoral retention to achieve high intratumoral accumulation. By virtue of surface borate esterfication, polyol chemotherapeutic drug (doxorubicin, DOX), and NO prodrug (β-galactosyl-diazeniumdiolate, Gal-NO) can be efficiently and stably conjugated on the surface of ZBN-HA (1.21 g DOX or 0.57 g Gal-NO per gram ZBN) without visible drug leakage, and the photopyrolysis of borate ester enables NIR-controlled drug release with high responsiveness and controllability. Combined chemothermal/gasothermal therapies based on ZBN-HA/DOX and ZBN-HA/NO nanomedicines eradicate primary tumors and interdict tumor metastasis by changing the tumor microenvironment and killing cancer cells in primary tumors. The developed NIR-photothermal MBene is confirmed as a versatile nanoplatform capable of high-efficacy tumor-targeted drug delivery and controlled drug release.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is estimated to affect a quarter of all population and represents a major health threat to all societies. Yet, currently no approved pharmacological treatment is available for MAFLD. H

Photothermal nanotheranostics, especially in the near infrared II (NIR-II) region, exhibits a great potential in precision and personalized medicine, owing to high tissue penetration of NIR-II light. NIR-II-photothermal nanoplatforms with high biocompatibility as well as high photothermal effect are urgently needed but rarely reported so far. Te nanomaterials possess high absorbance to NIR-II light but also exhibit high cytotoxicity, impeding their biomedical applications. In this work, the controllable incorporation of biocompatible Se into the lattice of Te nanostructures is proposed to intrinsically tune their inherent cytotoxicity and enhance their biocompatibility, developing TeSex nano-alloys as a new kind of theranostic nanoplatform. We have uncovered that the cytotoxicity of Te nanomaterials primarily derives from irreversible oxidation stress and intracellular imbalance of organization and energy, and can be eliminated by incorporating a moderate proportion of Se (x = 0.43). We have also discovered that the as-prepared TeSex nano-alloys have extraordinarily high NIR-II-photothermal conversion efficiency (77.2%), 64Cu coordination and computed tomography contrast capabilities, enabling high-efficacy multimodal photothermal/photoacoustic/positron emission tomography/computed tomography imaging-guided NIR-II-photothermal therapy of cancer. The proposed nano-alloying strategy provides a new route to improve the biocompatibility of biomedical nanoplatforms and endow them with versatile theranostic functions., A nano-alloying strategy is proposed to completely eliminate the toxicity of Te nanomaterials and simultaneously endow them with versatile theranostic functions by Se incorporation, realizing safe, precise and high-efficacy cancer treatment by multimodal PT/PA/CT/PET imaging-guided NIR-II-photothermal therapy.

Nano-mediated tumor tissue–cell–mitochondria–targeted multistage delivery and controlled release of CO augment therapy outcomes., CO gas molecule not only could selectively kill cancer cells but also exhibits limited anticancer efficacy because of the lack of active tumor-targeted accumulation capability. In this work, a multistage assembly/disassembly strategy is developed to construct a new intelligent nanomedicine by encapsulating a mitochondria-targeted and intramitochondrial microenvironment–responsive prodrug (FeCO-TPP) within mesoporous silica nanoparticle that is further coated with hyaluronic acid by step-by-step electrostatic assembly, realizing tumor tissue–cell–mitochondria–targeted multistage delivery and controlled release of CO in a step-by-step disassembly way. Multistage targeted delivery and controlled release of CO involve (i) the passive tumor tissue–targeted nanomedicine delivery, (ii) the active tumor cell–targeted nanomedicine delivery, (iii) the acid-responsive prodrug release, (iv) the mitochondria-targeted prodrug delivery, and (v) the ROS-responsive CO release. The developed nanomedicine has effectively augmented the efficacy and safety of CO therapy of cancer both in vitro and in vivo. The proposed multistage assembly/disassembly strategy opens a new window for targeted CO therapy.

Hydrogen therapy is an emerging and promising strategy for treatment of inflammation-related diseases owing to the excellent bio-safety of hydrogen molecules (H

By delivering the concept of clean hydrogen energy and green catalysis to the biomedical field, engineering of hydrogen-generating nanomaterials for treatment of major diseases holds great promise. Leveraging virtue of versatile abilities of Pd hydride nanomaterials in high/stable hydrogen storage, self-catalytic hydrogenation, near-infrared (NIR) light absorption and photothermal conversion, here we utilize the cubic PdH0.2 nanocrystals for tumour-targeted and photoacoustic imaging (PAI)-guided hydrogenothermal therapy of cancer. The synthesized PdH0.2 nanocrystals have exhibited high intratumoural accumulation capability, clear NIR-controlled hydrogen release behaviours, NIR-enhanced self-catalysis bio-reductivity, high NIR-photothermal effect and PAI performance. With these unique properties of PdH0.2 nanocrystals, synergetic hydrogenothermal therapy with limited systematic toxicity has been achieved by tumour-targeted delivery and PAI-guided NIR-controlled release of bio-reductive hydrogen as well as generation of heat. This hydrogenothermal approach has presented a cancer-selective strategy for synergistic cancer treatment., The tracking and targeted release of multi-agents to cooperatively treat cancer is a developing and evolving field. Here, the authors demonstrate the anticancer effects of cubic Pd hydride nanocrystals with photoacoustic imaging properties that can release hydrogen under an NIR trigger and have photothermal effects.

The recognized therapeutic benefits from carbon monoxide (CO) have caused booming attention to develop a CO therapy for various major diseases, such as cancer. However, the controlled release of CO gas and the monitoring of the CO release are vitally important to the on-demand CO administration for a safe and efficient therapy, but greatly challenging. In this work, a new CO-releasing nanocomplex was constructed by the adsorption and coordination of manganese carbonyl ([MnBr(CO)5 ], abbreviated as MnCO) with a Ti-based metal-organic framework (Ti-MOF) to realize an intratumoral H2 O2 -triggered CO release and real-time CO release monitoring by fluorescence imaging. A high CO prodrug loading capacity (0.532 g MnCO per gram Ti-MOF) is achieved due to the high surface area of Ti-MOF, and the intracellular H2 O2 -triggered CO release from the MnCO@Ti-MOF is realized to enable the nanocomplex selectively release CO in tumor cells and kill tumor cells rather than normal cells. Particularly significant is that the real-time fluorescence imaging monitoring of the CO release is realized based on an annihilation effect of the fluorescence after MnCO loading into Ti-MOF and an activation effect of the fluorescence after CO release from Ti-MOF. The quantitative relationship between the fluorescence intensity and the released CO amount is established in great favor of guiding on-demand CO administration. The results demonstrate the advantage of versatile MOFs for high efficient CO delivery and monitoring, which is critical for the improvement of the effectiveness of future therapeutic application.

Chimeric antigen receptor T cells (CAR-T cells) targeting of CD19 antigen has been proven to be effective and successful in B cell acute lymphoblastic leukemia. The traditional CAR delivery systems have several problems such as poor biosafety, low loading capacity, and low transfection efficiency. Utilization of nanocarriers for CAR delivery offers new possibilities for CAR-T treatment. In the present study, an anti-CD19 CAR expression lentivirus plasmid was constructed for CAR delivery and immunotherapy. In addition, a three-segment amphiphilic co-polymer, methoxy polyethylene glycol-branched polyethyleneimine-poly(2-ethylbutyl phospholane) (mPEG-bPEI-PEBP) was synthesized via click reaction as the carrier with cationic PEI, capable of delivering the CAR and packaging plasmids to co-transfect Jurkat cells and undergo expression. The PEBP and mPEG parts of the co-polymer provide hydrophobic and hydrophilic interfaces and lead to the co-polymer self-assembly into micelles in water and encapsulation of the DNA plasmids. The mPEG-bPEI-PEBP-DNA composites with different N/P ratios were incubated with the CD19 overexpression K562 cells to identify the CAR functions. The obtained CAR-Jurkat cells had the ability to secrete interferon-γ and interleukin-2. The cytotoxic effects to CD19-K562 cells suggest that the induced CAR-Jurkat cells have an excellent targeted antitumor activity.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is estimated to affect a quarter of all population and represents a major health threat to all societies. Yet, currently no approved pharmacological treatment is available for MAFLD. H2-rich water has recently been reported to reduce hepatic lipid accumulation in MAFLD patients but its efficacy is limited due to low H2 dosage. Increasing H2 dose may enhance its therapeutic effects but remains technically challenging. In this study, we designed and synthesized a hydrogen nanocapsule by encapsulating ammonia borane into hollow mesoporous silica nanoparticles to achieve ultrahigh and sustained H2 release in the gut. We then investigated its efficacy in treating early-stage MAFLD and other metabolic dysfunctions such as obesity and diabetes. The hydrogen nanocapsule attenuated both diet-induced and genetic mutation induced early-stage MAFLD, obesity, and diabetes in mice, without any tissue toxicity. Mechanistically, we discovered that sustained and ultrahigh H2 supply by hydrogen nanocapsule increased, among other species, the abundance of Akkermansia muciniphila, highlighting reshaped gut microbiota as a potential mechanism of H2 in treating metabolic dysfunctions. Moreover, hepatic transcriptome showed a reprogramed liver metabolism profile with reduced lipid synthesis and increased fatty acid metabolism.

Light-sensitive nanomaterial-released thermia is an emerging approach for cancer therapy. However, the therapeutic efficacy of this approach is generally modest and several challenging issues remain unresolved, including ineffective conversion from light to heat production, uncontrolled release of anticancer drugs, and non-specific delivery of nanomaterials to the tumor site. Here, we propose a new therapeutic concept by converting a photothermal nanomaterial to tumor cell-killing gas in the tumor microenvironment (TME) for gasothermal therapy. This novel strategy employed a chemical coordination (BPN-MnCO) between light-sensitive black phosphorous nanomaterial (BPN) and metal carbonyl (MnCO). The absorption of near-infrared red (NIR) light by BPN triggered the photochemical degradation of coordinated MnCO to produce a high concentration of carbon monoxide (CO) as well as hyperpyrexia in the local TME. Additionally, the surface coordination of MnCO protected BPN from biodegradation to achieve a long-lasting effect of heat production, which went through a feedback mechanism to effectively produce anticancer CO. In various preclinical cancer models, we showed that this approach nearly completely eradicated tumors without causing any notable adverse effects. Mechanistically, we discovered that BPN-generated heat inhibited the repair process of the CO-induced DNA damage and thus accelerated the ATM–GADD45–P53–Cyclin B cell death signaling. In summary, we provide compelling experimental evidence to support our new concept of gasothermal anticancer therapy that is likely to shift a new paradigm for effective treatment of cancer.

A facile and general coordination-precipitation method is developed to synthesize insoluble metal Roussin’s black salts (Me-RBSs) as a new type of NIR-responsive NORMs. The weak-field ligand coordination of metal+–RBS– brings a NIR absorption effect of Me-RBSs, and further gives rise to the NIR adsorption-dependent NIR-responsive NO release profile. Intratumoral NIR-responsive release of NO effectively inhibits the growth and metastasis of the metastatic breast cancer. Aqueous insolubility of Me-RBSs ensures lower cytotoxicity and higher thermostability compared with traditional soluble RBSs. This work establishes a new class of NIR-sensitive NO donors, and may spark new inspiration for designing intelligent gas-releasing molecules.

Nitric oxide (NO) has been well identified as a specific free radical molecule possessing wide-ranging therapeutic effects. Targeted delivery and controlled release of NO are highly desired to realize precision gas therapy, but are still challenging owing to the non-targetability and uncontrollability of NO itself. Herein, we propose a new concept of MRI-guided and ultrasound-triggered gas release for precision gas therapy. Based on this concept, we develop a novel ultrasound-responsive BNN-type NO-releasing molecule (NORM) and an advanced rattle-type nano-carrier of superparamagnetic iron oxide-encapsulated mesoporous silica nanoparticles (SPION@hMSN), and use them to construct a new intelligent nanomedicine (BNN6-SPION@hMSN) for the first time. The BNN6-SPION@hMSN nanomedicine exhibits excellent passive tumor-targeting capability, high MRI-guided tumor localization performance and a unique ultrasound-triggered NO release profile. The tumor-targeted, MRI-guided and ultrasound-triggered release profiles of the developed nanomedicine enable the tumor site-specific controlled release of NO in favor of high-efficacy and safe NO gas therapy of tumor.

H2O2-triggered release of CO: an intratumoral H2O2-responsive nanomedicine is constructed by effectively encapsulating the hydrophilic manganese carbonyl prodrug into an advanced hollow mesoporous silica nanoparticle carrier to realize selective killing of tumor cells, exhibiting high in vitro and in vivo efficacies of CO gas therapy.

Background: Rapid advance in biomedicine has recently vitalized the development of multifunctional two-dimensional (2D) nanomaterials for cancer theranostics. However, it is still challenging to develop new strategy to produce new types of 2D nanomaterials with flexible structure and function for enhanced disease theranostics. Method: We explore the monolayer Bi-anchored manganese boride nanosheets (MBBN) as a new type of MBene (metal boride), and discover their unique near infrared (NIR)-photothermal and photoacoustic effects, X-ray absorption and MRI imaging properties, and develop them as a new nanotheranostic agent for multimodal imaging-guided photothermal therapy of cancer. A microwave-assisted chemical etching route was utilized to exfoliate the manganese boride bulk into the nanosheets-constructed flower-like manganese boride nanoparticle (MBN), and a coordination-induced exfoliation strategy was further developed to separate the MBN into the dispersive monolayer MBBN by the coordination between Bi and B on the surface, and the B-OH group on the surface of MBBN enabled facile surface modification with hyaluronic acid (HA) by the borate esterification reaction in favor of enhanced monodispersion and active tumor targeting. Result: The constructed MBBN displays superior NIR-photothermal conversion efficiency (η=59.4%) as well as high photothermal stability, and possesses versatile imaging functionality including photoacoustic, photothermal, CT and T1-wighted MRI imagings. In vitro and in vivo evaluations indicate that MBBN had high photothermal ablation and multimodal imaging performances, realizing high efficacy of imaging-guided cancer therapy. Conclusion: We have proposed new MBene concept and exfloliation strategy to impart the integration of structural modification and functional enhancement for cancer theranostics, which would open an avenue to facile fabrication and extended application of multifunctional 2D nanomaterials.

Background To improve the outcome of cancer treatment, the combination of multiple therapy models has proved to be effective and promising. Gas therapy (GT) and chemodynamic therapy (CDT), mainly targeting the mitochondrion and nucleus, respectively, are two emerging strategy for anti-cancer. The development of novel nanomedicine for integrating these new therapy models is greatly significant and highly desired. Methods A new nanomedicine is programmed by successive encapsulation of MnO2 nanoparticles and iron carbonyl (FeCO) into mesoporous silica nanoparticle. By decoding the nanomedicine, acidity in the lysosome drives MnO2 to generate ROS, ·OH among which further triggers the decomposition of FeCO into CO, realizing the effective combination of chemodynamic therapy with gas therapy for the first time. Results Acidity in the TEM drives MnO2 to generate ROS, ∙OH among which further triggers the decomposition of FeCO into CO, realizing the effective combination of CDT and CDGT. The co-released ROS and CO do damage to DNA and mitochondria of various cancer cells, respectively. The mitochondrial damage can effectively cut off the ATP source required for DNA repair, causing a synergetic anti-cancer effect in vitro and in vivo. Conclusions The combination of CDT and CDGT causing a synergetic anti-cancer effect in vitro and in vivo. The proposed therapy concept and nanomedicine designing strategy might open a new window for engineering high-performance anti-cancer nanomedicine. Electronic supplementary material The online version of this article (10.1186/s12951-019-0507-x) contains supplementary material, which is available to authorized users.

The hydrogen molecule is recognized as a high potential to attenuate toxic side effects of chemotherapy and also enhance chemotherapeutic efficacy, and the development of a novel hydrogen-generating prodrug for facile, safe, and efficient hydrogen delivery is vitally important for combined hydrogenochemotherapy but is still challenging. Here, targeting gastric cancer, a 2D magnesium boride nanosheet (MBN) is synthesized as a new type of acid-responsive hydrogen-releasing prodrug by an ultrasound-assisted chemical etching route, which is used to realize hydrogenochemotherapy by combination of facile oral administration of polyvinylpyrrolidone (PVP)-encapsulating MBN (MBN@PVP) pills with routine intravenous injection of doxorubicin (DOX). The MBN@PVP pill has high stability in normal tissues/blood environments as well as high gastric acid-responsiveness with sustained release behavior, which matches well with its metabolism rate in the stomach in great favor of continuous and long-term hydrogen administration. Hydrogenochemotherapy with DOX+MBN@PVP has remarkably prolonged the survival time of gastric tumor-bearing mice by reducing the toxic side effects of chemotherapy. The mechanism for therapeutic synergy and side effect attenuation of hydrogenochemotherapy is discovered to be derived from the selectivity of hydrogen molecules in inhibiting aerobic respiration of gastric cells but activating aerobic respiration of normal cells including marrow mesenchymal stem cells and cardiac, hepatic, and splenic cells.

Additional file 1: Figure S1. Nitrogen adsorption–desorption isotherms. Figure S2. The standard curve of FeCO. Figure S3. UV spectra of the carrier, drug and nanomedicine. Figure S4. The ADBA standard curve for calculation of ROS concentration. Figure S5. The monitoring of ROS release in different pH PBSs using ADBA as probe by the UV method. Figure S6. The coumarin standard curve for calculation of ∙OH concentration. Figure S7. The monitoring of ∙OH release in different pH PBSs using coumarin as probe by the UV method. Figure S8. The monitoring of CO release in different ∙OH concentrations using Hb as probe by the UV method. Figure S9. The monitoring of CO release in different acidic solutions using Hb as probe by the UV method. Figure S10. Cytotoxicities of different concentrations of nanomedicines to various cancer cells. Figure S11. Histological examination of main organs (heart, liver, spleen, lung and kidney) from treated mice by the HE staining method. Figure S12. The weight change of 4T1 tumor-bearing mice during treatment. Figure S13. Blood biochemical analyses. Figure S14. The evaluation of standard haematology markers.

A new H

A series of pyrene derivatives with different asymmetrical substituents were successfully synthesized and characterized. The geometrical electronic structures of the asymmetrical pyrene derivatives were performed by density functional theory (DFT) calculations. The results of photophysical spectra and electrochemical analysis indicated that the optical or electric properties of the pyrene derivatives could be tuned by adjust the π-conjugation lengths of the substituents. Furthermore, through a phase exchange self-assembly method, the highly organized morphologies were observed by SEM.

The hydrogen molecule is recognized as a high potential to attenuate toxic side effects of chemotherapy and also enhance chemotherapeutic efficacy, and the development of a novel hydrogen-generating prodrug for facile, safe, and efficient hydrogen delivery is vitally important for combined hydrogenochemotherapy but is still challenging. Here, targeting gastric cancer, a 2D magnesium boride nanosheet (MBN) is synthesized as a new type of acid-responsive hydrogen-releasing prodrug by an ultrasound-assisted chemical etching route, which is used to realize hydrogenochemotherapy by combination of facile oral administration of polyvinylpyrrolidone (PVP)-encapsulating MBN (MBN@PVP) pills with routine intravenous injection of doxorubicin (DOX). The MBN@PVP pill has high stability in normal tissues/blood environments as well as high gastric acid-responsiveness with sustained release behavior, which matches well with its metabolism rate in the stomach in great favor of continuous and long-term hydrogen administration. Hydrogenochemotherapy with DOX+MBN@PVP has remarkably prolonged the survival time of gastric tumor-bearing mice by reducing the toxic side effects of chemotherapy. The mechanism for therapeutic synergy and side effect attenuation of hydrogenochemotherapy is discovered to be derived from the selectivity of hydrogen molecules in inhibiting aerobic respiration of gastric cells but activating aerobic respiration of normal cells including marrow mesenchymal stem cells and cardiac, hepatic, and splenic cells.