Notes

Recognition involving 3 defense molecular subtypes linked to immune system single profiles, immune checkpoints, along with clinical outcome throughout multiple myeloma.
The ligand-receptor PEC sensing strategy has promising potential for the detection of tumor cells and protein biomarkers.Carboxymethyl cellulose/agar-based functional halochromic films were fabricated by adding alizarin and grapefruit seed extract (GSE). The fillers were evenly dispersed in the polymer matrix to form compatible composite films. The addition of alizarin has improved the film's mechanical strength (20%) and water resistance (40%) with potent antioxidant and excellent color indicating properties. In contrast, GSE has imparted strong antibacterial and antioxidant activities to the film. Also, the addition of alizarin and GSE slightly improved the water vapor barrier properties but did not affect the thermal stability of the film. The composite film also exhibited UV blocking properties with adequate transparency. The composite film showed an excellent pH-dependent color change with color reversibility and color stability and a volatile gas detection function. The film also showed potent antimicrobial activity against foodborne pathogenic bacteria, Escherichia coli and Listeria monocytogenes, and showed an intense antioxidant action.We designed a biodegradable hybrid nanostructure for near-infrared (NIR)-induced photodynamic therapy (PDT) using an ultrasmall upconversion (UC) phosphor (β-NaYF4Yb3+, Er3+ nanoparticle NPs) and a hydrocarbonized rose bengal (C18RB) dye, a hydrophobized rose bengal (RB) derivative. The UC-NPs were encapsulated along with C18RB in the hydrophobic core of the micelle composed of poly(ethylene glycol) (PEG)-block-poly(ε-caprolactone) (PCL). The UC-NPs were well shielded from the aqueous environment, owing to the encapsulation in the hydrophobic PCL core, to efficiently emit green UC luminescence by avoiding the quenching by the hydroxyl groups. The hydrophobic part of C18 of C18RB worked well to be involved in the PCL core and located RB on the surface of the PCL core, making the efficient absorption of green light and the emission of singlet oxygen to surrounding water possible. Moreover, as the location is covered by PEG, the direct contact of RB to cells is prohibited to avoid their irradiation-free toxic effect on the cells. The hybrid nanostructure proved to be degradable by the hydrolysis of PEG-b-PCL. This degradation potentially results in renal excretion by the decomposition of the nanostructure into sub-10 nm size particles and makes them viable for clinical uses. These nanostructures can potentially be used for PDT of cancer in deep tissues.Phototherapy including photothermal therapy (PTT) and photodynamic therapy (PDT) uses photosensitizers and light to kill cancer cells and has become a promising therapeutic modality because of advantages such as minimal invasiveness and high cancer selectivity. However, PTT or PDT as a single treatment modality has insufficient therapeutic efficacy. Moreover, oxygen consumption by PDT activates angiogenic factors and leads to cancer recurrence and progression. Therefore, the therapeutic outcomes of phototherapy would be maximized by employing photosensitizers for concurrent PTT and PDT and suppressing angiogenic factors. Therefore, integrating photosensitive agents and antiangiogenic agents in a single nanoplatform would be a promising strategy to maximize the therapeutic efficacy of phototherapy. In this study, we developed hyaluronic acid-coated fluorescent boronated polysaccharide (HA-FBM) nanoparticles as a combination therapeutic agent for phototherapy and antiangiogenic therapy. Upon a single near-infrared laser irradiation, HA-FBM nanoparticles generated heat and singlet oxygen simultaneously to kill cancer cells and also induced immunogenic cancer cell death. Beside their fundamental roles as photosensitizers, HA-FBM nanoparticles exerted antiangiogenic effects by suppressing the vascular endothelial growth factor (VEGF) and cancer cell migration. In a mouse xenograft model, intravenously injected HA-FBM nanoparticles targeted tumors by binding CD44-overexpressing cancer cells and suppressed angiogenic VEGF expression. Upon laser irradiation, HA-FBM nanoparticles remarkably eradicated tumors and increased anticancer immunity. Given their synergistic effects of phototherapy and antiangiogenic therapy from tumor-targeting HA-FBM nanoparticles, we believe that integrating the photosensitizers and antiangiogenic agents into a single nanoplatform presents an attractive strategy to maximize the anticancer therapeutic efficacy of phototherapy.A biodegradable amphiphilic liquid polymer was designed to form self-emulsifying nanodroplets in water for delivering poorly soluble drugs. The polymer was composed of multiple short blocks of poly(ethylene glycol) (PEG) and poly(caprolactone) (PCL) connected through acid-labile acetal linkages. With an overall average molecular weight of over 18 kDa, the polymer remained as a viscous liquid under room and physiological temperatures. Dispersing the polymer in an aqueous buffer gave rise to highly stable micelle-like nanodroplets with an average size of approximately 15-20 nm. The nanodroplet dispersions underwent reversible temperature-sensitive aggregation with cloud points ranging from 45 to 50 °C, depending on polymer concentration. Nuclear magnetic resonance (NMR) and dynamic light scattering analyses revealed that while the nanodroplets were stable at pH 7.4 for several days, hydrolysis of the acetal linkages in the polymer backbone was much accelerated under mildly acidic pH 5.0, resulting in the formation of large microdroplets. Nile red (NR), a poorly water-soluble fluorophore, can be solubilized in the nanodroplets, and efficient intracellular delivery of NR was achieved. The hydrophobic indocyanine green (ICG) was also encapsulated in the nanodroplets. Near-infrared (NIR) fluorescence imaging and in vivo biocompatibility of the ICG-loaded nanodroplets were demonstrated in mice. In summary, the self-emulsifying nanodroplets of amphiphilic liquid polymer would be a promising material system for poorly soluble drug delivery and imaging in vivo.Delivering injectable microspheres in a minimally invasive way to repair complexly shaped tissue defects renders them attractive for clinical use. Especially, open porous microspheres that provide sufficient internal space for cell proliferation and nutrient diffusions can efficiently aid to completing reconstructions of tissue defects. In this work, chemically synthesized and biodegradable poly(4-hydroxybutyrate) (P4HB), which is the U.S. FDA-approved polyhydroxyalkanoate (PHA), was employed for fabricating open porous microspheres using a double-emulsion solvent evaporation method. The influences of fabrication parameters were discussed. It was found that the P4HB-based cell-free and growth factor-free open porous microspheres can enhance osteoblast differentiation of adipose-derived stem cells in vitro and accelerate rat calvarial bone-defect healing in vivo. These results demonstrated that the injectable open porous P4HB microspheres present a remarkable potential in bone tissue regeneration.In the treatment of tumor-targeted small-molecule anti-cancer drugs, antibody-mediated therapies, especially for antibody-drug conjugates (ADCs), have revealed great latent force. click here However, the therapeutic drugs provided by ADCs possess limitation. Considering that the combination of antibodies and nano-drugs can broaden their applicability in the field of tumor treatment, herein, we developed an antibody conjugated polymeric prodrug nanoparticles SAE-PEG-b-PBYP-ss-CPT for targeted camptothecin (CPT) delivery to liver tumor cells. The diblock copolymer was composed of PEG and biodegradable polyphosphoester (PBYP) containing alkynyl groups in the side chain. A derivative of CPT (CPT-ss-N3) was bonded to the PBYP via "click" reaction. The diethyl squarate (SAE) in the terminal of PEG chain was used as a functional group to bond with CD147 monoclonal antibody (CD147 mAb). The particle size and size distribution of the both nanoparticles, with antibody binding (namely CD147-CPT NPs) and without antibody (abbreviated as CPT-loaded NPs), were measured by dynamic light scattering (DLS). The morphologies of both two kinds of nanoparticles were observed by transmission electron microscope (TEM). The results of X-ray photoelectron spectroscopy (XPS) showed that CD147 mAb had been coupled to the surface of CPT-loaded NPs. Endocytosis test indicated that CD147-CPT NPs had higher uptake rate and accumulation in HepG2 cells than those of CPT-loaded NPs without antibodies, due to CD147 mAb can specifically bind to CD147 protein overexpressed in HepG2 cells. We establish a method to bond monoclonal antibodies to anti-cancer polymeric prodrugs, and endow biodegradable polymeric prodrugs with precise targeting functions to liver cancer cells.The antitumor efficacy of photodynamic therapy (PDT) is greatly impeded by the nonspecific targeting of photosensitizers and limited oxygen supply in hypoxic tumors. Aiming to overcome the problem, a dual-locked porphyrin/enzyme-loading zeolitic imidazolate framework (ZIF) nanoplatform was constructed for starvation therapy and O2 self-sufficient PDT. The fluorescence recovery and PDT of photosensitizers could be cooperatively triggered by dual pathological parameters, the low pH and overexpressed GSH in tumor tissues, which makes the PDT process conduct precisely in a tumor microenvironment. The cascade catalysis of glucose oxidase and catalase promotes the nanoplatform dissociation, inhibits the energy supply of tumors (starvation therapy), and provides enough O2 to ameliorate the hypoxia and enhance PDT efficacy. In vitro and in vivo studies were performed to confirm the high antitumor efficacy of the porphyrin/enzyme-loading ZIF nanoplatform. Thus, this work offers a path for precise and efficient PDT-based combination therapy against a hypoxia tumor.Exogenous photothermal agents absorbing in the second near-infrared optical window (NIR-II, 1000-1700 nm) have received much attention due to their use in noninvasive photothermal therapy. A small quantity of organic NIR-II photothermal agents have been exploited, and the development of organic NIR-II photothermal materials is an urgent need for biological applications. In this study, we designed and synthesized three dithiolene nickel(II) complexes with different ligands-bis(phenyl) dithiolene for NiBD-Ph, bis(fluorenyl) dithiolene for NiBD-Fl, and bis(carbazolyl) dithiolene for NiBD-Cz-and investigated their photophysical properties. These complexes exhibited ligand-dependent NIR absorption performance, centered at 854 nm for NiBD-Ph, 942 nm for NiBD-Fl, and 1010 nm for NiBD-Cz, respectively. NiBD-Cz is wrapped in ethylene oxide/propylene oxide block copolymer (F-127) through a hydrophilic-hydrophobic interaction to form water-soluble NiBD-Cz/F-127 nanoparticles (NiBD-Cz NPs), and the absorption peak of NiBD-Cz NPs are red-shifted to 1036 nm. NiBD-Cz NPs exhibit good dispersibility in water, robust photostability, and a high photothermal conversion efficiency (PCE) of 63.6% under 1064 nm laser irradiation, which is the highest PCE among metal bis(dithiolene) complexes up to now. The high PCE makes it possible to achieve better photothermal treatment effects even at low concentrations and under low-power laser irradiation.
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