Multifunctional nanosheets based on folic acid modified manganese oxide for tumor-targeting theranostic application.

It is highly desirable to develop smart nanocarriers with stimuli-responsive drug-releasing and diagnostic-imaging functions for cancer theranostics. Herein, we develop a reduction and pH dual-responsive tumor theranostic platform based on degradable manganese dioxide (MnO2) nanosheets. The MnO2 nanosheets with a size of 20-60 nm were first synthesized and modified with (3-Aminopropyl) trimethoxysilane (APTMS) to get amine-functionalized MnO2, and then functionalized by NH2-PEG2000-COOH (PEG). The tumor-targeting group, folic acid (FA), was finally conjugated with the PEGylated MnO2 nanosheets. Then, doxorubicin (DOX), a chemotherapeutic agent, was loaded onto the modified nanosheets through a physical adsorption, which was designated as MnO2-PEG-FA/DOX. The prepared MnO2-PEG-FA/DOX nanosheets with good biocompatibility can not only efficiently deliver DOX to tumor cells in vitro and in vivo, leading to enhanced anti-tumor efficiency, but can also respond to a slightly acidic environment and high concentration of reduced glutathione (GSH), which caused degradation of MnO2 into manganese ions enabling magnetic resonance imaging (MRI). The longitudinal relaxation rate r1 was 2.26 mM(-1) s(-1) at pH 5.0 containing 2 mM GSH. These reduction and pH dual-responsive biodegradable nanosheets combining efficient MRI and chemotherapy provide a novel and promising platform for tumor-targeting theranostic application.

The Application of Nanobody in CAR-T Therapy.

Chimeric antigen receptor (CAR) T therapy represents a form of immune cellular therapy with clinical efficacy and a specific target. A typical chimeric antigen receptor (CAR) construct consists of an antigen binding domain, a transmembrane domain, and a cytoplasmic domain. Nanobodies have been widely applied as the antigen binding domain of CAR-T due to their small size, optimal stability, high affinity, and manufacturing feasibility. The nanobody-based CAR structure has shown a proven function in more than ten different tumor-specific targets. After being transduced in Jurkat cells, natural killer cells, or primary T cells, the resulting nanobody-based CAR-T or CAR-NK cells demonstrate anti-tumor effects both in vitro and in vivo. Interestingly, anti-BCMA CAR-T modulated by a single nanobody or bi-valent nanobody displays comparable clinical effects with that of single-chain variable fragment (scFv)-modulated CAR-T. The application of nanobodies in CAR-T therapy has been well demonstrated from bench to bedside and displays great potential in forming advanced CAR-T for more challenging tasks.

Benzyl N'-benzhydrylidene-hydrazine-carbodithio-ate.

In the title mol-ecule, C(21)H(18)N(2)S(2), the C=N-N angle of 117.6 (2)° is significantly smaller than the ideal value of 120° expected for sp(2)-hybridized N atoms. This is probably a consequence of repulsion between the nitro-gen lone pairs and the adjacent N atom, as suggested in Zheng, Qiu, Lin & Liu [Acta Cryst. (2006), E62, o1913-o1914]. The two neighbouring benzene rings form a dihedral angle of 75.95 (3)° with each other, while subtending dihedral angles of 84.18 (3) and 8.44 (2)° with the third ring in the structure.

4-Chloro-N-(3-phenyl-allyl-idene)aniline.

In the title mol-ecule, C(15)H(12)ClN, the C=N and C=C bond lengths are 1.273 (2) and 1.324 (2) Å, respectively. The two aromatic rings form a dihedral angle of 3.27 (3)°.

Multifunctional nanoplatform for enhanced photodynamic cancer therapy and magnetic resonance imaging.

Co-delivery of photosensitizers and synergistic agents by one single nanoplatform is interesting for enhancing photodynamic therapy (PDT) of cancer. Here, a multifunctional nanoplatform for enhanced photodynamic therapy and magnetic resonance imaging of cancer was constructed. The poly (lactide-co-glycolide) (PLGA) nanoparticles (NPs) loaded with hematoporphyrin monomethyl ether (HMME) were coated with multifunctional manganese dioxide (MnO2) shells, which were designed as PLGA/HMME@MnO2 NPs. Once the NPs were effectively taken up by tumor cells, the intracellular H2O2 was catalysed by the MnO2 shells to generate O2. Meanwhile, the higher glutathione (GSH) promoted the degradation of MnO2 into Mn2+ ions with the ability of magnetic resonance (MR) imaging. After the degradation of outer layer, the release of photosensitizer was promoted. Under irradiation, the released HMME produced cytotoxic reactive oxygen species (ROS) to damage the tumor cells when the O2 was generated in the hypoxic tumor site. Furthermore, the decreased GSH level further inhibited the consumption of the produced ROS, which greatly enhanced the PDT efficacy. Therefore, this study suggested that this multifunctional system has the potential for enhanced photodynamic therapy and magnetic resonance imaging.

Manganese dioxide nanosheets-based redox/pH-responsive drug delivery system for cancer theranostic application.

The aim of this study was to construct redox- and pH-responsive degradable manganese dioxide (MnO2) nanosheets for cancer theranostic application. The small MnO2 nanosheets were synthesized, and then functionalized by hyaluronic acid (HA), demonstrating excellent stability and tumor-targeting ability. Cisplatin (cis-diamminedichloroplatinum [CDDP]) was absorbed by the nanosheets through a physical action, which was designed as MnO2/HA/CDDP. The prepared MnO2/HA/CDDP formulation was able to efficiently deliver CDDP to tumor cells in vitro and in vivo, resulting in improved therapeutic efficiency. Subsequently, they were triggered by lower pH and higher level of reduced glutathione to generate Mn(2+), enabling magnetic resonance imaging. The smart multifunctional system combining efficient magnetic resonance imaging and chemotherapy has the potential to be used as a tumor-targeting theranostic nanomedicine.

Gold nanostars mediated combined photothermal and photodynamic therapy and X-ray imaging for cancer theranostic applications.

Gold nanomaterials possess unique physical and chemical properties, which attracted much attention in recent years. As a new type of gold nanomaterials, gold nanostars (GNSTs) have been prepared and characterized in this study. GNSTs under near-infrared (NIR) light irradiation can exert not only cancer photothermal therapy via heat production but also photodynamic therapy via generation of reactive oxygen species. GNSTs were able to enter the cytoplasm as well as nuclei of human breast michigan cancer foundation-7 (MCF-7) cells. Under NIR light irradiation, GNSTs caused more severe DNA damage, arrest the cell cycle in G0/G1 phase, and reduce more cellular glutathione level, causing more severe apoptosis and cell death in vitro. Intratumoral injection of GNSTs with NIR light irradiation significantly inhibited tumor growth in vivo. In addition, GNSTs were demonstrated to be a contrast agent for X-ray imaging. All the in vitro and in vivo results showed that GNSTs can be used for the potential diagnosis and medical treatment of cancer.

The tumor-targeting core-shell structured DTX-loaded PLGA@Au nanoparticles for chemo-photothermal therapy and X-ray imaging.

In this study, an organic-inorganic hybrid nanocomposite was synthesized by deposition of Au onto the surface of docetaxel (DTX)-loaded poly (lactide-co-glycolide) (PLGA) nanoparticle cores to form the core-shell structured DTX-loaded PLGA@Au nanoparticles. The tumor targeting peptide, angiopep-2, was then introduced onto the gold nanoshell through Au-S bond, achieving drug delivery with active targeting capability. This novel system allowed combined chemotherapy and thermal therapy for cancer, resulting from DTX and gold nanoshell. The formation of tumor-targeting gold nanoshell surrounding PLGA nanocore, designated as ANG/GS/PLGA/DTX NPs, was confirmed by its surface plasmon resonance (SPR) band in the UV-Vis spectrum and by a transmission electron microscope (TEM). The release profiles of DTX from this system showed strong dependence on near-infrared (NIR) laser. Compared with DTX alone, the ANG/GS/PLGA/DTX NPs afforded much higher anti-tumor efficiency without obvious toxic effects. Besides, it also showed potential X-ray imaging ability. These results demonstrated that the tumor-targeting core-shell structured DTX-loaded PLGA@Au nanoparticles could be used as a multifunctional nanomaterial system with NIR-triggered drug-releasing properties for tumor-targeted chemo-photothermal therapy and theranostics.

Targeted Imaging and Chemo-Phototherapy of Brain Cancer by a Multifunctional Drug Delivery System.

The aim of this study was to develop multifunctional poly lactide-co-glycolide (PLGA) nanoparticles with the ability to simultaneously deliver indocyanine green (ICG) and docetaxel (DTX) to the brain by surface decoration with the brain-targeting peptide angiopep-2 to achieve combined chemo-phototherapy for glioma under near-infrared (NIR) imaging. ICG was selected as a near-infrared imaging and phototherapy agent and DTX was employed as a chemotherapeutic agent. ICG and DTX were simultaneously incorporated into PLGA nanoparticles with higher stability. These nanoparticles were further decorated with angiopep-2 via the outer maleimide group of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000]-maleinimide incorporated in the nanoparticles. The NIR image-guided chemo-phototherapy of the angiopep-2 modified PLGA/DTX/ICG nanoparticles (ANG/PLGA/DTX/ICG NPs) not only highly induced U87MG cell death in vitro, but also efficiently prolonged the life span of the brain orthotopic U87MG glioma xenograft-bearing mice in vivo. Thus, this study suggests that ANG/PLGA/DTX/ICG NPs have the potential for combinatorial chemotherapy and phototherapy for glioma.

[Prevalence survey on Cyclospora cayetanensis and Cryptosporidium ssp. in diarrhea cases in Yunnan Province].

OBJECTIVE: To investigate the prevalence and distribution characteristics of Cyclospora cayetanensis and Cryptosporidium ssp. infection in diarrhea cases of Yunnan Province. METHODS: To collect fresh faeces from diarrhea cases in 7 counties/cities, examine the specimens by direct smear with iodine staining and modified acid-fast staining. RESULTS: The infection rate of C. cayetanensis and Cryptosporidium ssp. was 3.97% and 5.29%, respectively. The infection rate of the two pathogenic coccidians was as high as 10.64% and 8.51% in preschool children. C. cayetanensis was found in 3 counties and Cryptosporidium in 6 counties. CONCLUSION: Both C. cayetanensis and Cryptosporidium ssp. are prevalent in Yunnan Province with the latter distributed more widely, and the two pathogens are more prevalent in preschool children.