Gold-based hybrid nanostructures: more than just a pretty face for combinational cancer therapy.

The early diagnosis together with an efficient therapy of cancer is essential to treat cancer patients and to enhance their quality of life. The use of nanostructures, as a newer technology, has demonstrated proven benefits as efficient cancer theranostic agents in numerous recent studies. Having a tunable surface plasmon resonance, gold nanostructures have been the subject of many recent studies as excellent imaging and photothermal therapy agents. However, the potential cytotoxicity and weak stability of gold nanostructures necessitate further modifications using biocompatible materials for biological applications. Based on the composition of the final structure, these gold-based hybrid nanostructures (GHNs) could be divided into five major groups; each of which has specific pros and cons. Understanding the strengths and weaknesses of each group helps scientists to optimize GHN designs with multiple functions by synergizing the benefits of different groups. This review aims to summarize the advancements in GHN design and provide a perspective view of future requirements for successful GHN-based targeted combinational cancer theranostic platforms.

Removal of bisphenol A in aqueous solution using magnetic cross-linked laccase aggregates from Trametes hirsuta.

Enzymatic removal of Bisphenol A (BPA), acknowledged as an environmentally friendly approach, is a promising method to deal with hard degradable contaminants. However, the application of "enzymatic treatment" has been limited due to lower operational stability and practical difficulties associated with recovery and recycling. Enzyme immobilization is an innovative approach which circumvents these drawbacks. In this study, laccase from Trametes hirsuta was used for BPA removal. Amino-functionalized magnetic Fe3O4 nanoparticles were synthesized via the co-precipitation method followed by surface modification with (3-aminopropyl)trimethoxysilane (APTMS). The as-prepared nanoparticles were utilized for the immobilization of laccase with the magnetic cross-linked enzyme aggregates method (MCLEAs). Activity recovery of 27% was achieved, while no immobilized laccase was observed in the cross-linked enzyme aggregates method. The performance of immobilized laccase was measured by analyzing the degradation of BPA pollutant. The maximum removal efficiency of 87.3% was attained with an initial concentration of 60 ppm throughout 11 h.

Doxorubicin/Cisplatin-Loaded Superparamagnetic Nanoparticles As A Stimuli-Responsive Co-Delivery System For Chemo-Photothermal Therapy.

INTRODUCTION: To date, numerous iron-based nanostructures have been designed for cancer therapy applications. Although some of them were promising for clinical applications, few efforts have been made to maximize the therapeutic index of these carriers. Herein, PEGylated silica-coated iron oxide nanoparticles (PS-IONs) were introduced as multipurpose stimuli-responsive co-delivery nanocarriers for a combination of dual-drug chemotherapy and photothermal therapy. METHODS: Superparamagnetic iron oxide nanoparticles were synthesized via the sonochemical method and coated by a thin layer of silica. The nanostructures were then further modified with a layer of di-carboxylate polyethylene glycol (6 kDa) and carboxylate-methoxy polyethylene glycol (6 kDa) to improve their stability, biocompatibility, and drug loading capability. Doxorubicin (DOX) and cisplatin (CDDP) were loaded on the PS-IONs through the interactions between the drug molecules and polyethylene glycol. RESULTS: The PS-IONs demonstrated excellent cellular uptake, cytocompatibility, and hemocompatibility at the practical dosage. Furthermore, in addition to being an appropriate MRI agent, PS-IONs demonstrated superb photothermal property in 0.5 W/cm2 of 808 nm laser irradiation. The release of both drugs was effectively triggered by pH and NIR irradiation. As a result of the intracellular combination chemotherapy and 10 min of safe power laser irradiation, the highest cytotoxicity for iron-based nanocarriers (97.3±0.8%) was achieved. CONCLUSION: The results of this study indicate the great potential of PS-IONs as a multifunctional targeted co-delivery system for cancer theranostic application and the advantage of employing proper combination therapy for cancer eradication.

Fabrication of hierarchically porous silk fibroin-bioactive glass composite scaffold via indirect 3D printing: Effect of particle size on physico-mechanical properties and in vitro cellular behavior.

In order to regenerate bone defects, bioactive hierarchically scaffolds play a key role due to their multilevel porous structure, high surface area, enhanced nutrient transport and diffusion. In this study, novel hierarchically porous silk fibroin (SF) and silk fibroin-bioactive glass (SF-BG) composite were fabricated with controlled architecture and interconnected structure, by combining indirect three-dimensional (3D) inkjet printing and freeze-drying methods. Further, the effect of 45S5 Bioactive glass particles of different sizes (<100 nm and 6 µm) on mechanical strength and cell behavior was investigated. The results demonstrated that the hierarchical structure in this scaffold was composed of two levels of pores in the order of 500-600 µm and 10-50 µm. The prepared SF-BG composite scaffolds utilized by nano and micro particles possessed mechanical properties with a compressive strength of 0.94 and 1.2 MPa, respectively, in dry conditions. In a wet condition, the hierarchically porous scaffolds did not exhibit any fluctuation after compression load cell and were incredibly flexible, with excellent mechanical stability. The SF-BG composite scaffold with nanoparticles presented a significant 50% increase in attachment of human bone marrow stem cells in comparison with SF and SF-BG scaffold with microparticles. Moreover, SF-BG scaffolds promoted alkaline phosphatase activity as compared to SF scaffolds without BG particles on day 14. In brief, the 3D porous silk fibroin-based composites containing BG nanoparticles with excellent mechanical properties are promising scaffolds for bone tissue regeneration in high load-bearing applications.

Inorganic nanomaterials for chemo/photothermal therapy: a promising horizon on effective cancer treatment.

During the last few decades, nanotechnology has established many essential applications in the biomedical field and in particular for cancer therapy. Not only can nanodelivery systems address the shortcomings of conventional chemotherapy such as limited stability, non-specific biodistribution and targeting, poor water solubility, low therapeutic indices, and severe toxic side effects, but some of them can also provide simultaneous combination of therapies and diagnostics. Among the various therapies, the combination of chemo- and photothermal therapy (CT-PTT) has demonstrated synergistic therapeutic efficacies with minimal side effects in several preclinical studies. In this regard, inorganic nanostructures have been of special interest for CT-PTT, owing to their high thermal conversion efficiency, application in bio-imaging, versatility, and ease of synthesis and surface modification. In addition to being used as the first type of CT-PTT agents, they also include the most novel CT-PTT systems as the potentials of new inorganic nanomaterials are being more and more discovered. Considering the variety of inorganic nanostructures introduced for CT-PTT applications, enormous effort is needed to perform translational research on the most promising nanomaterials and to comprehensively evaluate the potentials of newly introduced ones in preclinical studies. This review provides an overview of most novel strategies used to employ inorganic nanostructures for cancer CT-PTT as well as cancer imaging and discusses current challenges and future perspectives in this area.

Evaluation of cellular attachment and proliferation on different surface charged functional cellulose electrospun nanofibers.

Fabrication and characterization of different surface charged cellulose electrospun scaffolds including cellulose acetate (CA), cellulose, carboxymethyl cellulose (CMC) and quaternary ammonium cationic cellulose (QACC) for biomedical applications have been reported in this research. Several instrumental techniques were employed to characterize the nanofibers. MTT assay and cell attachment studies were also carried out to determine the cytocompatibility, viability and proliferation of the scaffolds. Fabricated CA, cellulose, CMC and QACC nanofibers had 100-600 nm diameter, -9, -1.75, -12.8, + 22 mV surface potential, 2.5, 4.2, 7.2, 7 MPa tensile strength, 122, 320, 515, 482 MPa Young modules, 430, 530, 670 and 642% water uptake and 92°, 58°, 45°, 47° contact angle respectively. The findings showed that cell adhesion and proliferation is strongly enhanced on the modified surfaces with quaternary ammonium and carboxymethyl groups. We believe the use of cationic and anionic surface modified cellulose electrospun nanofibers presents promising materials for biomedical applications.

A Biomimetic Heparinized Composite Silk-Based Vascular Scaffold with sustained Antithrombogenicity.

Autologous grafts, as the gold standard for vascular bypass procedures, associated with several problems that limit their usability, so tissue engineered vessels have been the subject of an increasing number of works. Nevertheless, gathering all of the desired characteristics of vascular scaffolds in the same construct has been a big challenge for scientists. Herein, a composite silk-based vascular scaffold (CSVS) was proposed to consider all the mechanical, structural and biological requirements of a small-diameter vascular scaffold. The scaffold's lumen composed of braided silk fiber-reinforced silk fibroin (SF) sponge covalently heparinized (H-CSVS) using Hydroxy-Iron Complexes (HICs) as linkers. The highly porous SF external layer with pores above 60 µm was obtained by lyophilization. Silk fibers were fully embedded in scaffold's wall with no delamination. The H-CSVS exhibited much higher burst pressure and suture retention strength than native vessels while comparable elastic modulus and compliance. H-CSVSs presented milder hemolysis in vitro and significant calcification resistance in subcutaneous implantation compared to non-heparinized ones. The in vitro antithrombogenic activity was sustained for over 12 weeks. The cytocompatibility was approved using endothelial cells (ECs) and vascular smooth muscle cells (SMCs) in vitro. Therefore, H-CSVS demonstrates a promising candidate for engineering of small-diameter vessels.

A new bifunctional hybrid nanostructure as an active platform for photothermal therapy and MR imaging.

As a bi-functional cancer treatment agent, a new hybrid nanostructure is presented which can be used for photothermal therapy by exposure to one order of magnitude lower laser powers compared to similar nanostructures in addition to substantial enhancment in magnetic resonance imaging (MRI) contrast. This gold-iron oxide hybrid nanostructure (GIHN) is synthesized by a cost-effective and high yield water-based approach. The GIHN is sheilded by PEG. Therefore, it shows high hemo and biocompatibility and more than six month stability. Alongside earlier nanostructures, the heat generation rate of GIHN is compareable with surfactnat-capped gold nanorods (GNRs). Two reasons are behind this enhancement: Firstly the distance between GNRs and SPIONs is adjusted in a way that the surface plasmon resonance of the new nanostructure is similar to bare GNRs and secondly the fraction of GNRs is raised in the hybrid nanostructure. GIHN is then applied as a photothermal agent using laser irradiation with power as low as 0.5 W.cm(-2) and only 32% of human breast adenocarcinoma cells could survive. The GIHN also acts as a dose-dependent transvers relaxation time (T2) MRI contrast agent. The results show that the GINH can be considered as a good candidate for multimodal photothermal therapy and MRI.