Green dual-template synthesis of AgPd core-shell nanoparticles with enhanced electrocatalytic activity.

A key challenge in developing an ethanol oxidation reaction is nontoxic fabrication of highly active stable and low-cost catalysts. Here we design a green synthetic strategy of AgPd bimetallic nanosphere by a dual-template cascade method. The Pd nanoshell is firstly prepared using Vapreotide acetate as a primary template, and then the Ag nanoshell acts as a secondary template for the distribution of AgPd alloy nanoparticles. The AgPd nanoparticles have core-shell structures and various sizes, and their shell thicknesses are tuned by controlling the amount of PdCl2. The six different samples are prepared, named AgPd-1, AgPd-2, AgPd-3, AgPd-4, AgPd-5, and AgPd-6, respectively. The mass current density of AgPd-5, is higher 3.87 times that of commercial Pd/C, and exhibits the best ethanol oxidation reaction activity and long-term stability. The main reasons are that the AgPd-5 possessed excellent specific surface area due to their rough structure, and Ag can remove more CO-like species. This is the first time a Vapreotide acetate/Ag-template method has been used to synthesize a AgPd core-shell structure, which would have broad application prospects for direct ethanol fuel cells.

Direct synthesis of ultralong platinum nanowires with prominent electrocatalytic performance using lanreotide biotemplate.

Due to the dependence on the morphology, size and composition of Pt-based nanomaterials on their catalytic properties, rational design can improve the utilization efficiency and catalytic performance of Pt. As inspired by this, the ultralong Pt nanowires (ULPtNWs) with a diameter of 25 nm were prepared by a mild, green and direct peptide mediated biological template method. Impressively, ULPtNWs with a large electrochemical active surface area (57.2 m2 g-1) were obtained, exhibiting that the peak current density for the methanol oxidation was approximately three-fold better than commercial Pt/C catalyst owing to the high aspect ratio (1.6 × 103 or more). Additionally, the excellent poison resistance of the product was demonstrated, which can be attributed to the high (111) plane. These enhancements indicate that ULPtNWs as a promising catalyst have broad application prospects in the field of direct methanol fuel cells or other electrocatalysis.

Trimodal synergistic antitumor drug delivery system based on graphene oxide.

A multifunctional antitumor drug delivery system was synthesized based on graphene oxide (GO) for near-infrared (NIR) light controlling chemotherapeutic/photothermal (PTT) /photodynamic (PDT) trimodal synergistic therapy. The system named ICG-Wed-GO was formed by co-loading wedelolactone (Wed) and indocyanine green (ICG) on the surface of GO through π-π stacking interaction. Under NIR laser irradiation, ICG-Wed-GO could effectively absorb and transform optical energy to heat, generate reactive oxygen species (ROS) to ablating and damage tumor cells. The temperature of ICG-Wed-GO solution reached up to 79.4 °C in 10 min with NIR irradiation. In in vitro and in vivo study, ICG-Wed-GO showed excellent antitumor effect. After 14-day treatment of ICG-Wed-GO with NIR laser irradiation, the tumor disappeared completely on tumor-bearing mice. The low biotoxicity of ICG-Wed-GO was also proved. The system achieved the synergistic trimodal chemotherapeutic/photothermal/photodynamic treatment and demonstrated excellent antitumor effect, which is expected to have a greater potential for cancer therapy.

Gold-nanobranched-shell based drug vehicles with ultrahigh photothermal efficiency for chemo-photothermal therapy.

Development of combined chemo-photothermal nanoplatform is of great interest for enhancing antitumor efficacy. Herein, a multifunctional drug delivery system was synthesized based on gold-nanobranched coated betulinic acid liposomes (GNBS-BA-Lips) for chemo-photothermal synergistic therapy. In this system, GNBS-BA-Lips exhibited broad near-infrared (NIR) absorption, preferable photothermal response and good photostability under NIR irradiation. Importantly, the gold-nanobranched nanostructure possessed high photothermal conversion efficiency (η = 55.7%), and the temperature change (ΔT) reached 43.2 °C after laser irradiation for 5 min. Upon NIR irradiation, the nanocarriers apparently endowed higher cell uptake, resulting in an enhanced intracellular drug accumulation. Furthermore, the tumor growth inhibition ratio achieved from chemo-photothermal therapy of GNBS-BA-Lips was 86.9 ±â€¯1.1%, which was higher than that of the chemotherapy or photothermal therapy alone, showing an outstanding synergistic anticancer effect. Our data suggested that the nanoplatform should be considered as a critical platform in the development of cancer multi-mode therapies.

Doxorubicin/gold nanoparticles coated with liposomes for chemo-photothermal synergetic antitumor therapy.

Hybrid liposome/metal nanoparticles are promising candidate drug-carriers for therapy of various diseases due to their unique photothermal effect. In this study, self-crystallized gold nanoparticles (Au NPs) and doxorubicin (DOX) were co-encapsulated within liposomes (Au/DOX-Lips) by thin film hydration and gel separation technology. The surface plasmon resonance bands of drug-carriers were controllable in the near-infrared (NIR) zone. When the complex liposome/metallic hybrids were irradiated by NIR light, they displayed higher endocytosis efficiency following the fracture of liposomal membranes and the release of Au NPs. Then, the Au NPs penetrated further into deeper tumor tissue to accomplish photothermal treatment. The Au/DOX-Lips showed an excellent antitumor effect, whose inhibition rate for tumor cells was up to 78.28%. In experiments on mice bearing tumors, the Au/DOX-Lips treated mice exhibited superior tumor suppression. This novel drug system provides huge potential for biomedical application.

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.

Combined Near Infrared Photothermal Therapy and Chemotherapy Using Gold Nanoshells Coated Liposomes to Enhance Antitumor Effect.

Novel antitumor system based on the targeting photothermal and pH-responsive nanocarriers, gold nanoshells coated oleanolic acid liposomes mediating by chitosan (GNOLs), is designed and synthesized for the first time. The GNOLs present spherical and uniform size (172.03 nm) with zeta potential (20.7 ± 0.4 mV), which are more easily accumulated in tumor. Meanwhile, the GNOLs exhibit a slow and controlled release of oleanolic acid at pH 7.4, as well as a rapid release at pH 5.5, which is beneficial for tumor-targeting drug release. Under near infrared (NIR) irradiation, hyperthermia can be generated by activated gold nanoshells to perform photothermal therapy effect, which triggers drug release from the carriers by activating the gel to liquid crystalline phase transition of the liposomes. Moreover, the NIR assisting drug release can be easily and selectively activated locally due to the spatially and real-timely controllable property of light. The experimental results also verify that the GNOLs with NIR irradiation achieve more ideal antitumor effects than other oleanolic acid formulations in vitro and in vivo. Hence, the drug delivery system exhibits a great potential in chemo-photothermal antitumor therapy.

Gold Nanoshells: Combined Near Infrared Photothermal Therapy and Chemotherapy Using Gold Nanoshells Coated Liposomes to Enhance Antitumor Effect (Small 30/2016).

Gold nanoshell coated oleanolic acid liposomes mediating by chitosan (GNOLs), are designed and successfully synthesized for the first time by D. Gao and co-workers on page number 4103. An excellent near infrared (NIR) photothermal effect, pH-responsive drug controlled release and tumor targeting properties are demonstrated. By combining NIR photothermal therapy and chemotherapy, the smart drug delivery system exhibits a superior antitumor property in vitro and in vivo.

Nanomagnetic liposome-encapsulated parthenolide and indocyanine green for targeting and chemo-photothermal antitumor therapy.

Aim: To synthesize a drug-delivery system with chemo-photothermal function and magnetic targeting, to validate its antitumor effect. Materials & methods: Parthenolide (PTL), employing chemotherapy and indocyanine green (ICG) providing phototherapy, were encased separately in the lipid and aqueous phases of liposomes (Lips). The Fe3O4 nanoparticles (MNPs), endowing magnetic targeting, were modified on the surface of Lips. The antitumor effects were investigated in vitro and in vivo. Results: ICG-PTL-Lips@MNPs showed outstanding synergistic antitumor efficacy in vitro and in vivo. Especially, after 14-day treatment, the tumor volumes decreased significantly and the biotoxicity was very low. Conclusion: The designed ICG-PTL-Lips@MNPs possess synergistic effects of chemotherapy, photothermal and targeting therapy, which are expected to provide an alternative way to further improve antitumor efficacy.

Sequential Intra-Intercellular Delivery of Nanomedicine for Deep Drug-Resistant Solid Tumor Penetration.

Cells in the center of solid tumors have always been an abyss untouched by treatments because of their deep location and increased drug resistance. Herein, we designed a rational strategy for sequential intra-intercellular delivery of nanomedicine to deep sites of drug-resistant solid tumors. In our formulation, dopamine and hemoglobin were polymerized to form a smart nanocarrier (PDA/Hb). Subsequently, the doxorubicin and nitric oxide donor were connected on the surface of PDA/Hb to obtain D/N-PDA/Hb. Ultimately, the hyaluronic acid was combined with D/N-PDA/Hb to form D/N-PDA/Hb@HA. Concretely, acidic and neutral environments of tumor cells were treated as a switch to turn on or off the drug release of a nanodrug. Meanwhile, the generation of nitric oxide in situ was exploited to favor the lysosomal escape of nanocarriers and overcome the drug resistance of deep solid tumor cells. The results indicated that the nanodrug based on sequential intra-intercellular delivery showed exciting penetration efficiency and resistance reversal of solid tumors. Conventional nanodrug delivery was highly dependent on the enhanced permeability and retention (EPR) effect and limited by tumorous interstitial fluid pressure. Plenty of drugs stayed on the surface of solid tumors, and the infiltrated drugs were inefficient due to strict resistance. To conquer this dilemma, this work proposed a new mechanism reversing the EPR effect for drug delivery, leading to better penetration and resistance reversal of solid tumors.

Sensitive measurement of tumor markers somatostatin receptors using an octreotide-directed Pt nano-flakes driven electrochemical sensor.

Tumor markers play an important role in the early diagnosis and therapeutic effect monitoring of tumors. An electrochemical biosensor was developed based on multi-branched gold nanoshells (BGSs) and octreotide (OCT) functionalized Pt nano-flakes (PtNFs) modified electrodes, which was used for detection of tumor-specific markers to evaluate tumor cells. Sandwich-type nano-hybrid materials were prepared by layer-by-layer modification. First, reduced graphene oxide (RGO) and BGSs were modified as electronic materials onto glassy carbon electrodes (GCE). This modified electrode has strong electron transfer capability and large electrode surface area. The OCT was then anchored to the surface of BGSs to sensitively detect Somatostatin receptors (SSTRs) on the surface of HeLa cells. In addition, PtNFs were synthesized using a dual-template method, and OCT template on the surface of PtNFs, as an adsorption bioprobe, was used to reduce the H2O2 and amplify the electrochemical signal of biosensor. The proposed biosensor can be applied to the quantitative broad linear range of HeLa cells covering from 10 to 1 × 106 cells mL-1 (R2 = 0.9998) and the limit of detection (LOD) was 2 cells mL-1. The experimental results also show that the sensor has good stability, biocompatibility and high selectivity, which has great potential for clinical application.

Near-Infrared Responsive Bimetallic Nanovesicles for Enhanced Synergistic Chemophotothermal Therapy.

Limited therapeutic effects and obvious side effects are two critical problems affecting tumor therapy. Herein, we designed an ingenious nanocarrier, platinum/gold bimetallic-nanoshell-coated triptolide liposomes (Pt@Au-TP-Lips), to achieve enhanced chemophotothermal therapy against cancer. Compared to conventional gold nanoflower structures, the platinum/gold bimetallic (Pt@Au) core-shells exhibited broader near-infrared (NIR) absorption due to the ultrastrong plasmonic coupling effect. With NIR light irradiation, the Pt@Au nanostructure could efficiently and sustainably convert light energy into substantial heat. The ultrahigh photothermal conversion efficiency (56.5%) of Pt@Au-TP-Lips was significantly higher than that of gold nanoflowers (35.7%). Specifically, hyperthermia could induce a phase change in the liposome membrane to accelerate the release of triptolide (TP); meanwhile, it could ablate tumor cells directly and facilitate the cellular uptake of drugs to enhance chemotherapy. More importantly, owing to the cooperation of TP and platinum, Pt@Au-TP-Lips exhibited significant tumor growth suppression with a high inhibitory rate of 90.7%, achieving superior chemophotothermal combination therapy. This work provides new insight into the development of a cooperative theranostic agent for oncotherapy.

A chemo-photothermal synergetic antitumor drug delivery system: Gold nanoshell coated wedelolactone liposome.

In this study, an antitumor drug delivery system, gold nanoshell coated wedelolactone liposomes (AuNS-Wed-Lip), were designed and synthesized. In the drug delivery system, wedelolactone liposome and gold-nanoshell were linked by l-cysteine, which had been shown an effective nanocarrier for antitumor drug delivery, on-demand drug release, and phototherapy under near-infrared (NIR) light irradiation. It was capable of absorbing 780-850 nm NIR light and converting light energy to heat rapidly. The hyperthermia promoted wedelolactone release rapidly from the systems. The release amount of AuNS-Wed-Lip under NIR irradiation reached up to 97.34% over 8 h, achieving the on-demand drug release. Moreover, a high inhibition rate up to 95.73% for 143B tumor cells by AuNS-Wed-Lip upon laser irradiation at 808 nm was observed. The excellent inhibition efficacy was also displayed in vivo antitumor study with S180 tumor-bearing mice. The results demonstrated that AuNS-Wed-Lip, as an antitumor drug delivery system, achieved chemo-photothermal synergetic effect, which has great potential in cancer therapy.

Dual-template cascade synthesis of highly multi-branched Au nanoshells with ultrastrong NIR absorption and efficient photothermal therapeutic intervention.

With the rapid development of photothermal therapy (PTT) in cancer treatment, it is necessary to obtain effective plasma-responsive tunable photothermal transducing agents. Inspired by the peptide-directed hierarchical mineralized Ag nanocages (Ag NCs), scientists designed a new duel-template cascade preparation method, and novel unique multi-branched gold nanoshells (BGSs) were successfully prepared under mild conditions using green strategy. The length, density and diameter of the branches were tuned, which led to the adjustment of the surface plasma response of the nanostructure. Because of the hierarchical structure and anisotropic surface, an obvious red shift of the local surface plasmon resonance spectrum was observed for the branched Au nanoshells. The excellent photothermal conversion efficiency (70.9%) and photo-induced heating responsive curves proved the superior photothermal conversion performance and photothermal stability of BGSs. The in vitro and in vivo results indicated that the heat generated by the intense NIR absorption of BGSs can selectively destroy cancer cells under laser irradiation. The nanostructures with ultrastrong absorption have promising prospects in tumor therapy.

Dual-targeting liposomes for enhanced anticancer effect in somatostatin receptor II-positive tumor model.

AIM: We developed octreotide-modified magnetic liposomes (OMlips) as dual-targeting drug carriers to enhance the drug accumulation in tumor site. MATERIALS & METHODS: Octreotide acts as a modified ligand for receptor-mediated targeting and the coated Fe3O4 nanoparticles offer the magnetic targeting property. SSTR2 overexpressed A549 cells and S180 cells were chosen to explore the targeting ability and antitumor effect of the oleanolic acid (OA)-loaded OMlips in vitro and in vivo. RESULTS: The OMlips platform significantly improves the targeting, penetrating and accumulation of OA at the SSTR2 overexpressed cells and SSTR2-positive tumor-bearing mice. CONCLUSION: The OA-loaded OMlips have better antitumor effect and lower systemic toxicity. Such a receptor-mediated and magnetically-orienting dual-targeting drug nanocarriers may have great potentials in clinical practice.

Multistimuli-responsive drug vehicles based on gold nanoflowers for chemophotothermal synergistic cancer therapy.

AIM: To design and synthesize a novel multistimuli-responsive drug vehicle based on gold nanoflowers (AuNFs) for chemophotothermal synergistic cancer therapy. MATERIALS & METHODS: Multistimuli-responsive drug-delivery system based on doxorubicin (DOX)/polydopamine (PDA)-functionalized AuNFs (Lan-AuNFs@PDA/DOX) was prepared. The structural characteristics, photothermal properties and stimuli-responsive drug release properties of Lan-AuNFs@PDA/DOX were evaluated. Antitumor studies in vivo and in vitro were performed. RESULTS: Lan-AuNFs@PDA/DOX exhibited uniform morphology, excellent biocompatibility and photothermal conversion efficiency, which could also respond to stimulus including near infrared light and pH to trigger on demand drug release. The excellent synergistic therapeutic efficacy was confirmed both in vitro and in vivo. CONCLUSION: Lan-AuNFs@PDA/DOX would be a promising drug carrier, endowing a great potential for multistimuli-responsive chemophotothermal synergistic cancer therapy.

Self-Assembly of Stimuli-Responsive Au-Pd Bimetallic Nanoflowers Based on Betulinic Acid Liposomes for Synergistic Chemo-Photothermal Cancer Therapy.

Synergistic cancer therapy through the combination of chemotherapy with photothermal therapy has been gained more and more insights. Bimetallic nanostructures with near-infrared (NIR) plasmonic responses are considered prime candidates based on their superior photothermal conversion properties. Herein, novel poly branched Au-Pd bimetallic-nanoflowers-coated betulinic acid liposomes (BA-Lips@Pd@Au NFs) were designed and developed. The as-prepared BA-Lips@Pd@Au NFs with optimal size (144.4 nm) possessed good photostability under NIR-irradiation, high photothermal conversion efficiency (64.6%), and good biocompatibility. Moreover, the hyperthermia of drug delivery induced by NIR-irradiation dramatically improved the cell uptake of nanocapsules and enhanced the chemotherapeutic efficacy of tumor. Upon illumination by NIR light, the BA-Lips@Pd@Au NFs exhibited prominent synergetic effects of chemo-photothermal therapy with a tumor inhibition ratio (91.7%), which was higher than that of chemotherapy or photothermal therapy alone. Therefore, this rational design of nanocapsule with stimuli-responsive capability showed a versatile strategy to provide smart nanocapsule paradigms for cancer therapy.

Gold nanoshell coated thermo-pH dual responsive liposomes for resveratrol delivery and chemo-photothermal synergistic cancer therapy.

Stimuli-responsive drug delivery and release have a great significance in cancer therapy. Herein, a multifunctional responsive drug carrier was designed and developed by loading resveratrol (Res) in chitosan (CTS) modified liposomes, and coated by gold nanoshells (GNS@CTS@Res-lips). The resultant GNS@CTS@Res-lips possess broad near-infrared (NIR) absorbance, high capability, stability, and also high photothermal conversion ability for efficient photothermal therapy (PTT) applications. In addition, the GNS@CTS@Res-lips exhibit the on-demand pH/photothermal-sensitive drug release, and a high loading capacity of Res. Under NIR laser irradiation, the drug delivery system could significantly enhance the cellular uptake of drugs. More importantly, compared to the single chemotherapy or PTT, the carriers with NIR irradiation displayed a higher therapeutic effect for HeLa cells. Therefore, the GNS@CTS@Res-lips with a combination of chemotherapy and PTT will show great potential for application in cancer therapy.

Antitumor drug effect of betulinic acid mediated by polyethylene glycol modified liposomes.

Betulinic acid (BA), as a natural pentacyclic lupine-type triterpene, principally derives from bark of white birch, due to its potent pharmacological properties and low side-effect, which has been demonstrated a prominent efficiency on cancer therapy. However, the poor solubility and low bioavailability limit its pharmaceutical effect. Herein, we reported the rapid efficient synthesis of the polyethylene glycol modified (PEGylated) BA liposomes using ethanol injection technique for the first time. In the study, hydrophobic BA was encapsulated in the lipid bilayer of liposomes, meanwhile hydrophilic PEG layer covered the surface of liposomes. The mean diameter of PEGylated BA liposomes was 142nm, which can effectively accumulate in the tumor tissues. In vitro drug release study showed that the PEGylated BA liposomes had a better sustained drug release effect than BA liposomes. The PEGylated BA liposomes also exhibited a better tumor inhibitory effect compared with those of free BA or BA liposomes in vitro and in vivo experiments. Therefore, the PEGylated BA liposomes could serve as a better alternative for the cancer therapy in future.