Polymyxin E biomineralized and doxorubicin-loaded gold nanoflowers nanodrug for chemo-photothermal therapy.

Gold nanoparticles are a kind of good photothermal agents. However, gold nanoparticle photothermal agents have low photothermal conversion efficiency and low tumor inhibiting ability. To overcome these problems, polymyxin E (PE) biomineralized and doxorubicin-loaded gold nanoflowers (DOX-SH@AuNFs) nanodrug was synthesized by the green synthesis method using the biological antimicrobial peptide PE as a stabilizer and grower of crystal seed, and doxorubicin-thiol (DOX-SH) was further loaded on the gold nanoparticles through the Au-S bond. The final DOX-SH@AuNFs displayed a wide absorption band in the UV-Vis spectra, and their photothermal conversion efficiency was 33.9%. Furthermore, the inhibition rate of DOX-SH@AuNFs on A549 cells was as high as 80.1% under the irradiation of near-infrared light at 808 nm. The tumor inhibition rate of DOX-SH@AuNFs was as high as 87.81% in vivo experiments. The high tumor suppression rate was attributed to the high photothermal conversion ability of DOX-SH@AuNFs and the delivery of doxorubicin. Taken together, the method of preparing DOX-SH@AuNFs provides a new idea for the treatment of cancer by photothermal therapy and chemotherapy synergistic system.

Long-circulation zwitterionic dendrimer nanodrugs for phototherapy of tumors.

The development of stealth and effective antitumor nanodrugs has been drawing great attention. Herein, generation five poly(amide amine) dendrimer (G5 PAMAM) was modified by zwitterionic material carboxybetaine methacrylamide (CBMAA) on its surface to prepare zwitterionic dendrimer (G5-CBMAAn). The results showed that G5-CBMAA30 had the longest blood circulation time due to its thickest zwitterionic layer, and its residual rate after injection into mice at 2 and 12 h was as high as 47.22 % and 14.37 %, respectively. Nanodrug G5-CBMAA30-ICG was prepared by containing indocyanine green (ICG) in the cavity of G5-CBMAA30. G5-CBMAA30-ICG had better tumor targeting ability and antitumor effect than free ICG in mice after laser irradiation, and the tumor inhibition rate was 96.6 % after 14 days' treatment. The prepared G5-CBMAA30-ICG has great potential applications in the field of antitumor by phototherapy.

Biomineralized synthesis of palladium nanoflowers for photothermal treatment of cancer and wound healing.

Photothermal therapy uses photothermal agents (PTAs) to convert light energy to heat energy under near-infrared light to kill local tumors in cancer patients or speed up wound healing in diabetic patients. However, it is difficult to achieve high photothermal conversion efficiency for most of PTAs. Herein, daptomycin (Dap) micelles-stabilized palladium nanoflowers (Dap-PdNFs) were prepared for the first time. The palladium nanoflowers (PdNFs) inside of the Dap-PdNFs were 106 nm. The temperature of the Dap-PdNFs solution quickly rose from 26.8 °C to 52.0 °C within 10 min under irradiation with high photothermal conversion efficiency up to 38%. In addition, the cell viability of HeLa cells and HT-29 cells of Dap-PdNFs exceeded 95% in the absence of near-infrared light, indicating that Dap-PdNFs had good biocompatibility. Meanwhile, the inhibition rate of Dap-PdNFs on HeLa cells was as high as 71.2% under irradiation of 808 nm near-infrared light. More importantly, Dap-PdNFs had a good healing effect on wounds of diabetic mice under irradiation of 808 nm near-infrared light. In short, this research provides a facile method for the application of Dap-PdNFs in safe and efficient tumor treatment and wound healing.

"Stealth" dendrimers with encapsulation of indocyanine green for photothermal and photodynamic therapy of cancer.

Poly(amido amine) dendrimers and indocyanine green have inevitable interaction with proteins and cells, which induces biological toxicity and reduces therapeutic efficacy in vivo. To overcome these shortcomings, a new drug delivery system G5MEK7C(n)-ICG with a "stealth" layer was prepared. The surface of G5MEK7C(n)-ICG was modified with double-layer super hydrophilic zwitterionic materials. In the "stealth" double-layer structure, the outer layer was consisted of zwitterionic Glu-Lys-Glu-Lys-Glu-Lys-Cys (EK7) peptide, and the inner layer was composed of amino and carboxyl groups with a ratio of 1:1. DLS results showed that the average hydrodynamic size of G5MEK7C(n)-ICG was about 25-30 nm, and the zeta potential was proven to undergo a slight charge reversal with the increasing pH values of solutions. Furthermore, G5MEK7C(n)-ICG exhibited excellent biocompatibility to red blood cells and proteins resistance. Photothermal and photodynamic experiments demonstrated that G5MEK7C(n)-ICG had a good photothermal conversion effect and generated singlet oxygen (1O2) under laser irradiation. The MTT and hemolysis results showed that the toxicity of G5 PAMAM was significantly reduced after modification double-layer structure. Cytotoxicity studies and flow cytometry showed G5MEK7C(70)-ICG under laser irradiation had a good effect on killing A549 cells. More importantly, the tumor inhibition rate of mice treated with G5MEK7C(70)-ICG (under laser irradiation) was 78.2% in vivo, which was higher than that of mice treated with free ICG. Compared with free ICG, G5MEK7C(70)-ICG caused less damage to the liver according to the enzyme activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Therefore, dendrimers modified with a zwitterionic double layer will be a promising candidate as a drug delivery system.

Synthesis of gold nanoflowers stabilized with amphiphilic daptomycin for enhanced photothermal antitumor and antibacterial effects.

The development of effective agents for cancer therapy and inhibition of bacterial infection has drawn a great deal of interest. Photothermal therapy has been widely used for the thermal ablation of tumor cells. In addition, antibiotics have the ability to inhibit the growth of bacteria. Thus, the combination of photothermal therapy and antibiotics may be one of the methods to address the problem. Herein, it is the first time that daptomycin (Dap) micelles were used as the template and reducing agents to prepare stable daptomycin-gold nanoflowers (Dap-AunNFs) under mild conditions. The energy dispersive spectrometer (EDS) spectrum and X-ray diffraction (XRD) spectrum indicated that Dap-AunNFs were successfully prepared. When the molar ratio of HAuCl4 to Dap was 6, the gold nanoparticles inside of Dap-AunNFs were about 80 nm with flower-like shape. In addition, the photothermal conversion efficiency of Dap-Au6NFs was about 40%. More importantly, Dap-Au6NFs inhibited the growth of tumors and bacteria under the radiation of near-infrared light at 808 nm. The prepared Dap-Au6NFs could be used as photothermal antitumor and antibacterial agents in the future.

Green synthesis of palladium nanoparticles using lentinan for catalytic activity and biological applications.

The green synthesis of palladium nanoparticles (Pd NPs) for catalysis and biological applications has been gaining great interest. To replace complex plant extracts, lentinan (LNT) may be a good reducing and stabilizing agent. In this work, a simple and green method using LNT to reduce and stabilize palladium Pd NPs was verified. The resulting LNT stabilized palladium nanoparticles (Pd n -LNT NPs) were characterized by UV-Vis spectroscopy, DLS, TEM, and XPS. The results indicated that Pd NPs inside of Pd n -LNT NPs had a small size (2.35-3.32 nm). Pd n -LNT NPs were stable in solution for 7 days. In addition, Pd n -LNT NPs had higher catalytic activity towards the reduction of 4-nitrophenol than other catalysts. More importantly, Pd n -LNT NPs had negligible cytotoxicity towards cells and showed good antioxidant activity. Taken together, the prepared Pd n -LNT NPs have great potential bio-related applications.

Curcumin induces therapeutic angiogenesis in a diabetic mouse hindlimb ischemia model via modulating the function of endothelial progenitor cells.

BACKGROUND: Neovascularization is impaired in diabetes mellitus, which leads to the development of peripheral arterial disease and is mainly attributed to the dysfunction of endothelial progenitor cells (EPCs). Previous studies proved the promotional effect of curcumin on neovascularization in wound healing of diabetes. Thus, we hypothesize that curcumin could promote neovascularization at sites of hindlimb ischemia in diabetes and might take effect via modulating the function of EPCs. METHODS: Streptozotocin-induced type 1 diabetic mice and nondiabetic mice both received unilateral hindlimb ischemic surgery. Curcumin was then administrated to the mice by lavage for 14 days consecutively. Laser Doppler perfusion imaging was conducted to demonstrate the blood flow reperfusion. Capillary density was measured in the ischemic gastrocnemius muscle. In addition, angiogenesis, migration, proliferation abilities, and senescence were determined in EPCs isolated from diabetic and nondiabetic mice. Quantitative PCR was then used to determine the mRNA expression of vascular endothelial growth factor (VEGF) and angiopoetin-1 (Ang-1) in EPCs. RESULTS: Curcumin application to type 1 diabetic mice significantly improved blood reperfusion and increased the capillary density in ischemic hindlimbs. The in-vitro study also revealed that the angiogenesis, migration, and proliferation abilities of EPCs and the number of senescent EPCs were reversed by curcumin application. Quantitative PCR confirmed the overexpression of VEGF-A and Ang-1 in EPCs after curcumin treatment. CONCLUSION: Curcumin could enhance neovascularization via promoting the function of EPCs in a diabetic mouse hindlimb ischemia model.

Gold nanoshell-based betulinic acid liposomes for synergistic chemo-photothermal therapy.

A novel synthesis approach is first developed to fabricate a multifunctional smart nanodrug delivery system: gold nanoshell-coated betulinic acid liposomes (AuNS-BA-Lips) mediated by a glutathione. The AuNS-BA-Lips exhibited good size distribution (149.4±2.4nm), preferable photothermal conversion ability and synergistic chemo-photothermal therapy. Additionally, the absorption wavelength of AuNS-BA-Lips showed a significantly red-shifted to near infrared (NIR) region, which can strongly absorbed NIR laser and efficiently convert it into localized heat, thus providing controlled drug release and antitumor thermotherapy. Moreover, the nanocarriers excited by NIR light significantly promoted cell uptake compared to those without irradiation, resulting in an enhanced intracellular drug accumulation. Upon NIR irradiation, the AuNS-BA-Lips showed highly efficient antitumor effects on tumor-bearing mice with an inhibition rate of 83.02%, thus demonstrating a remarkable synergistic therapeutic effect of chemotherapy and thermotherapy. Therefore, this work provides new insight into developing a multifunctional antitumor drug.