Project description:The low efficiency of photodynamic therapy (PDT) is caused by tumor hypoxia and the adaptive immune resistance/evasion of tumor cells, while the currently emerging immune checkpoint therapy restores the intrinsic immune capacities but can't directly attack the tumor cells. Methods: Herein we report an integrated nanoplatform that combines PDT with immunotherapy to enhance photodynamic therapeutic effects and simultaneously inhibit tumor cells resistance/evasion. To achieve this, we fabricated Mn@CaCO3/ICG nanoparticles and loaded them with PD-L1-targeting siRNA. Results: Thanks to the protection of CaCO3 on the loaded ICG and the oxygen produced by MnO2, an enhanced photodynamic therapeutic effect in vitro was observed. In vivo experiments demonstrated that the nanoplatform could efficiently deliver the loaded drug to the tumor tissues and significantly improve tumor hypoxia, which further contributes to the therapeutic effect of PDT in vivo. Moreover, the synergistic benefits derived from the siRNA, which silenced the checkpoint gene PD-L1 that mediates the immune resistance/evasion, resulted in a surprising therapeutic effect to rouse the immune system. Conclusions: The combination treatment strategy has great potential to be developed as a new and robust method for enhanced PDT therapy with high efficiency and a powerful antitumor immune response based on PD-L1 blockade.
Project description:The combination of chemotherapy and photodynamic therapy provides a promising approach for enhanced tumor eradication by overcoming the limitations of each individual therapeutic modality. However, tumor is pathologically featured with extreme hypoxia together with the adaptable overexpression of anti-oxidants, such as glutathione (GSH), which greatly restricts the therapeutic efficiency. Here, a combinatorial strategy was designed to simultaneously relieve tumor hypoxia by self-oxygenation and reduce intracellular GSH level to sensitize chemo-photodynamic therapy. In our system, a novel multi-functional nanosystem based on MnO2-doped graphene oxide (GO) was developed to co-load cisplatin (CisPt) and a photosensitizer (Ce6). With MnO2 doping, the nanosystem was equipped with intelligent functionalities: (1) catalyzes the decomposition of H2O2 into oxygen to relieve the tumor hypoxia; (2) depletes GSH level in tumor cells, and (3) concomitantly generates Mn2+ to proceed Fenton-like reaction, all of which contribute to the enhanced anti-tumor efficacy. Meanwhile, the surface hyaluronic acid (HA) modification could facilitate the targeted delivery of the nanosystem into tumor cells, thereby resulting in amplified cellular toxicity, as well as tumor growth inhibition in nude mice model. This work sheds a new light on the development of intelligent nanosystems for synergistic combination therapy via regulating tumor microenvironment.
Project description:(19)F magnetic resonance imaging (MRI) is a powerful noninvasive, sensitive, and accurate molecular imaging technique for early diagnosis of diseases. The major challenge of (19)F MRI is signal attenuation caused by the reduced solubility of probes with increased number of fluorine atoms and the restriction of molecular mobility. Herein, we present a versatile one-pot strategy for the fabrication of a multifunctional nanoprobe with high (19)F loading (∼2.0 × 10(8 19)F atoms per Cu1.75S nanoparticle). Due to the high (19)F loading and good molecular mobility that results from the small particle size (20.8 ± 2.0 nm) and ultrathin polymer coating, this nanoprobe demonstrates ultrahigh (19)F MRI signal. In vivo tests show that this multifunctional nanoprobe is suitable for (19)F MRI and photothermal therapy. This versatile fabrication strategy has also been readily extended to other single-particle nanoprobes for ablation and sensitive multimodal imaging.
Project description:Recently, the widespread use of antibiotics is becoming a serious worldwide public health challenge, which causes antimicrobial resistance and the occurrence of superbugs. In this context, MnO2 has been proposed as an alternative approach to achieve target antibacterial properties on Streptococcus mutans (S. mutans). This requires a further understanding on how to control and optimize antibacterial properties in these systems. We address this challenge by synthesizing δ-MnO2 nanoflowers doped by magnesium (Mg), sodium (Na), and potassium (K) ions, thus displaying different bandgaps, to evaluate the effect of doping on the bacterial viability of S. mutans. All these samples demonstrated antibacterial activity from the spontaneous generation of reactive oxygen species (ROS) without external illumination, where doped MnO2 can provide free electrons to induce the production of ROS, resulting in the antibacterial activity. Furthermore, it was observed that δ-MnO2 with narrower bandgap displayed a superior ability to inhibit bacteria. The enhancement is mainly attributed to the higher doping levels, which provided more free electrons to generate ROS for antibacterial effects. Moreover, we found that δ-MnO2 was attractive for in vivo applications, because it could nearly be degraded into Mn ions completely following the gradual addition of vitamin C. We believe that our results may provide meaningful insights for the design of inorganic antibacterial nanomaterials.
Project description:Coupling between thermal and charge transport in crystalline materials has always been one of the greatest challenges in understanding the underlying physics of thermoelectric materials. In this sense, CaO(CaMnO3)m Ruddlesden-Popper layered perovskites, comprising m perovskite subcells separated by CaO planes, exhibit intriguing thermal and electronic transport properties that can be tuned by altering their crystal periodicities. Applying the well-established phonon glass electron crystal (PGEC) concept enables us to increase the transparency of these CaO planes to electron transport at the same time while preserving their opacity to phonon transport. First-principles calculations indicate that the total local potential at CaO planes, where Y substitutes for Ca, is lower by ca. 50% compared to La substitution. Measurements of the electrical conductivity and Seebeck coefficients for Ca2-xRxMnO4 (R = La or Y; x = 0.01, 0.05, 0.1, and 0.15) bulk materials in the range of 300-1000 K confirm that compounds doped with Y exhibit higher electrical conductivity values than their La-doped counterparts. We attribute this to lower polaron hopping energy values (up to 23%) evaluated using the small polaron hopping model. This study introduces an original way to employ the PGEC approach for thermoelectric oxides.
Project description:The development of targeted nanoprobes is a promising approach to cancer diagnostics and therapy. In the present work, a novel multifunctional photo/magnet-diagnostic nanoprobe (MNPs-PEG2K-FA@Ce6) has been developed. This nanoprobe is built using folic acid (FA), bifunctional polyethylene glycol (PEG2K) and photosensitizer chlorin e6 (Ce6). The MNPs-PEG2K-FA@Ce6 nanoprobes are superparamagnetic, can be synthesized on a large scale by a one-pot hydrothermal process without further surface modification and are stable in an aqueous environment for eight months. Compared with free Ce6 nanoprobes in vitro studies, the MNPs-PEG2K-FA@Ce6 nanoprobes significantly enhance cellular uptake efficiency and promote the effectiveness of photodynamic therapy (PDT) with the assistance of 633 nm laser irradiation. The unique nanoprobes show superior penetration and a retention time of more than six days with less accumulation in the liver allowing highly effective tumor recognition and monitoring. Additionally, there was little damage to healthy organs or tissues. These exciting new nanoprobes could be potential building blocks to develop new clinical therapies and translational medicine.
Project description:Extensive research indicates that graphene oxide (GO) can effectively deliver photosensitives (PSs) by π-π stacking for photodynamic therapy (PDT). However, due to the tight complexes of GO and PSs, the fluorescence of PSs are often drastically quenched via an energy/charge transfer process, which limits GO-PS systems for photodiagnostics especially in fluorescence imaging. To solve this problem, we herein strategically designed and prepared a novel photo-theranostic agent based on sinoporphyrin sodium (DVDMS) loaded PEGylated GO (GO-PEG-DVDMS) with improved fluorescence property for enhanced optical imaging guided PDT. The fluorescence of loaded DVDMS is drastically enhanced via intramolecular charge transfer. Meanwhile, the GO-PEG vehicles can significantly increase the tumor accumulation efficiency of DVDMS and lead to an improved PDT efficacy as compared to DVDMS alone. The cancer theranostic capability of the as-prepared GO-PEG-DVDMS was carefully investigated both in vitro and in vivo. Most intriguingly, 100% in vivo tumor elimination was achieved by intravenous injection of GO-PEG-DVDMS (2 mg/kg of DVDMS, 50 J) without tumor recurrence, loss of body weight or other noticeable toxicity. This novel GO-PEG-DVDMS theranostics is well suited for enhanced fluorescence imaging guided PDT.
Project description:With the fast bloom of flexible electronics and green vehicles, it is vitally important to rationally design and facilely construct customized functional materials with excellent mechanical properties as well as high electrochemical performance. Herein, by utilizing two modern industrial techniques, digital light processing (DLP) and chemical vapor deposition (CVD), a unique 3D hollow graphite foam (HGF) is demonstrated, which shows a periodic porous structure and robust mechanical properties. Finite element analysis (FEA) results confirm that the properly designed gyroidal porous structure provides a uniform stress area and mitigates potential structural failure caused by stress concentrations. A typical HGF can show a high Young's modulus of 3.18 MPa at a low density of 48.2 mg cm-3. The porous HGF is further covered by active MnO2 material with a high mass loading of 28.2 mg cm-2 (141 mg cm-3), and the MnO2/HGF electrode still achieves a satisfactory specific capacitance of 260 F g-1, corresponding to a high areal capacitance of 7.35 F cm-2 and a high volumetric capacitance of 36.75 F cm-3. Furthermore, the assembled quasi-solid-state asymmetric supercapacitor also shows remarkable mechanical properties as well as electrochemical performance.
Project description:The need for alternative strategies to fight bacteria is evident from the emergence of antimicrobial resistance. To that respect, photodynamic antimicrobial chemotherapy steadily rises in bacterial eradication by using light, a photosensitizer and oxygen, which generates reactive oxygen species that may kill bacteria. Herein, we report the encapsulation of 5,10,15,20-tetrakis(4-hydroxyphenyl)-21H,23H-porphyrin into acetylated lignin water-dispersible nanoparticles (THPP@AcLi), with characterization of those systems by standard spectroscopic and microscopic techniques. We observed that THPP@AcLi retained porphyrin's photophysical/photochemical properties, including singlet oxygen generation and fluorescence. Besides, the nanoparticles demonstrated enhanced stability on storage and light bleaching. THPP@AcLi were evaluated as photosensitizers against two Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa, and against three Gram-positive bacteria, Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecalis. THPP@AcLi were able to diminish Gram-positive bacterial survival to 0.1% when exposed to low white LED light doses (4.16 J/cm2), requiring concentrations below 5 μM. Nevertheless, the obtained nanoparticles were unable to diminish the survival of Gram-negative bacteria. Through transmission electron microscopy observations, we could demonstrate that nanoparticles did not penetrate inside the bacterial cell, exerting their destructive effect on the bacterial wall; also, a high affinity between acetylated lignin nanoparticles and bacteria was observed, leading to bacterial flocculation. Altogether, these findings allow to establish a photodynamic antimicrobial chemotherapy alternative that can be used effectively against Gram-positive topic infections using the widely available natural polymeric lignin as a drug carrier. Further research, aimed to inhibit the growth and survival of Gram-negative bacteria, is likely to enhance the wideness of acetylated lignin nanoparticle applications.
Project description:Doxorubicin-loaded MnO2@zeolitic imidazolate framework-8 (DOX/MnO2@ZIF-8) nanoparticles, a smart multifunctional therapeutic platform, were prepared for the treatment of lung cancer. The morphology, structure, and redox and photothermal properties of MnO2@ZIF-8 were characterized by the corresponding methods. The anticancer drug DOX released from the DOX/MnO2@ZIF-8 nanoparticles was measured. The cell viability of Lewis lung cancer (LLC) cells treated with MnO2@ZIF-8 or DOX/MnO2@ZIF-8 nanoparticles was determined using the cell counting kit-8 (CCK-8) method. The cellular uptake of DOX/MnO2@ZIF-8 nanoparticles into LLC cells was observed using a confocal laser scanning microscope. TUNEL staining was performed to evaluate the in vivo therapeutic efficacy of DOX/MnO2@ZIF-8 nanoparticles. The results showed that the as-prepared MnO2@ZIF-8 nanoparticles had an average particle size of 155.59 ± 13.61 nm and the DOX loading efficiency was 12 wt %. MnO2@ZIF-8 could react with H2O2 to generate O2 and showed a great photothermal conversion effect both in vitro and in vivo. Up to 82% of total DOX could be released from DOX/MnO2@ZIF-8 nanoparticles at pH = 5.0. The CCK-8 assay showed that MnO2@ZIF-8 had low cytotoxicity to LLC cells, while DOX/MnO2@ZIF-8 can significantly reduce the cell viability. DOX/MnO2@ZIF-8 can be accumulated in LLC cells over time. Compared with PBS and DOX/MnO2@ZIF-8 groups, the mice in the DOX/MnO2@ZIF-8 + NIR group had the most apoptotic cells and significantly reduced tumor volume. In conclusion, these findings suggest that the as-prepared MnO2@ZIF-8 nanoparticles with synergetic therapeutic effects by photothermal therapy and improved tumor microenvironment and as a pH-responsive nanocarrier for delivering the nonspecific anticancer drug DOX might be applied in the treatment of lung cancer.