Journal of interdisciplinary nanomedicine最新文献

Natural killer (NK) cells are at the forefront of immunotherapies, as they have potent innate cytolytic effects on cancer cells. The success of NK cell therapies requires that they overcome immunosuppression in the tumor microenvironment. Tumors produce immunosuppressive factors like transforming growth factor beta (TGF-β) that inhibit the effector functions of NK cells. Silencing of TGF-beta signaling in NK cells is a potential approach to enhance their functions. However, transfection of NK cells by conventional methods is challenging. Here, we report the development of a nanoparticle (NP) system that delivers small interfering RNA for the TGF-β receptor 2 (TGFBR2) into NK cells to restore their activation against cancer cells. Manganese dioxide NPs were synthesized by the reduction of potassium permanganate by poly (allylamine), which effectively complexed siRNA and protected it from degradation. The NPs were cytocompatible with NK cells and, upon loading with TGFBR2 siRNA, resulted in a 90% knockdown of the TGFBR2 receptor. NP-mediated TGFBR2 receptor knockdown protected NK cells against TGF-β suppression, which was studied in both two-dimensional and three-dimensional lung cancer cell culture systems. Namely, NK cells treated with TGFBR2 siRNA loaded NPs demonstrated higher interferon gamma production, infiltration, and killing of lung cancer cells compared with control NK cells. This study demonstrates the feasibility of NP-mediated RNA interference in NK cells to increase their resilience to the immunosuppressive environments in solid tumors.

In the last years, there has been an alarming increase in antibiotic resistance by pathogenic microbes, which has become a major public health concern. There is a great interest in developing new antimicrobial for reducing the impact. Silver nanoparticles (AgNPs) as antibacterial agents are currently being studied to be used to fight these pathogenic microbes. The aim of the present study was to synthesize AgNPs of different sizes through the use of microwave and determine their antimicrobial activities. Synthesis of size-dependent l-glutathione-capped spherical nanoparticles through one-pot microwave synthesis was achieved, and their antimicrobial properties were determined. Different sizes of AgNPs between 5–10, 15–35, and 50–80 nm were made by varying the concentration of silver nitrate and using sodium borohydride (NaBH₄) as a reducing agent. l-glutathione was used to stabilize the AgNPs to prevent them from aggregation in the colloidal solution. The synthesized AgNPs showed ultraviolet absorption at around 400 nm with high concentration of AgNO₃ having sharp peaks. The formed particles were crystalline in nature with uniform spherical shape. The formed AgNPs were of crystalline size of 9.94, 18.45, 34.96, 52.40, and 58.50 nm. Fourier transform infrared analysis confirmed conjugation of glutathione as a capping agent to AgNPs as the result of the formed spectra showing the absence of ─SH stretch. The high temperature generated by microwave helped to synthesize nanoparticles within a short time and by varying the concentration of AgNO₃ helped obtain the desired particle size. Glutathione conjugated well with AgNPs as a result of interaction of negative thiol resulting to colloidal stabilization and reduced aggregation. The antibacterial activity of AgNPs was found to be size dependent with the smaller size of 9.94 nm being more efficient than 18.45, 34.96, 52.40, and 58.50 nm against the tested strains Bacillus subtilis (ATCC 6633), Escherichia coli (ATCC 25922), Salmonella spp. (ATCC 700623), and Staphylococcus aureus (ATCC 25923). Of the four stains, E. coli was found to be the least affected by all three different particle sizes of the synthesized AgNPs.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), causes the most human deaths than any other diseases from a single infectious agent. Treatments are long and costly and have many associated side effects. Intracellular bacilli are slow growing and difficult to target, which is augmenting the emergence of multi-drug resistance. A hallmark trait of TB is the formation of granulomas, chronic cellular aggregates, which limit bacterial growth but provides a survival reservoir where bacilli may disseminate from. Targeting intracellular Mtb is challenging, but nanomedicine may offer a solution. Nanomedicine is a significantly growing research area and offers the potential for specific disease targeting, dosage reduction, and intracellular drug delivery. This review discusses the application of the various forms of nanomedicine towards targeting of Mtb.

The therapeutic potential of plumbagin, a naphthoquinone extracted from the officinal leadwort with anticancer properties, is hampered by its failure to specifically reach tumours at a therapeutic concentration after intravenous administration, without secondary effects on normal tissues. Its use in clinic is further limited by its poor aqueous solubility, its spontaneous sublimation, and its rapid elimination in vivo. We hypothesize that the entrapment of plumbagin within liposomes grafted with transferrin, whose receptors are overexpressed on many cancer cells, could result in a selective delivery to tumours after intravenous administration. The objectives of this study were therefore to prepare and characterize transferrin-targeted liposomes entrapping plumbagin and to evaluate their therapeutic efficacy in vitro and in vivo. The entrapment of plumbagin in transferrin-bearing liposomes led to an increase in plumbagin uptake by cancer cells and improved antiproliferative efficacy and apoptosis activity in B16-F10, A431, and T98G cell lines compared with that observed with the drug solution. In vivo, the intravenous injection of transferrin-bearing liposomes entrapping plumbagin led to tumour suppression for 10% of B16-F10 tumours and tumour regression for a further 10% of the tumours. By contrast, all the tumours treated with plumbagin solution or left untreated were progressive. The animals did not show any signs of toxicity. Transferrin-bearing liposomes entrapping plumbagin are therefore highly promising therapeutic systems that should be further optimized as a therapeutic tool for cancer treatment.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been considered as a potential anticancer agent owing to its selectivity for malignant cells. However, its clinical use remains limited because of its poor efficacy. Attempts to increase its antitumor activity include, among others, its functionalization by nanoparticles (NPs). In the present study, TRAIL was grafted onto magnetic spinel iron oxide NPs of defined core size, 10 and 100 nm on average, to see whether the size of the resulting nanovectors, NV10 and NV100, respectively, might affect TRAIL efficacy and selectivity. Apoptosis induced by NV10 and NV100 was higher than by TRAIL alone in both HCT116 and HepG2 cells. At equimolar concentrations, neither the nanovectors nor the corresponding NPs displayed cytotoxicity towards normal primary hepatocytes or TRAIL receptor-deficient HCT116 cells. NV100 exhibited superior proapoptotic activity than NV10, as evidenced by methylene blue and annexin V staining. Consistently, both caspase activation and TRAIL death-induced signaling complex formation, as assessed by immunoblot analysis, were found to be increased in cells treated with NV100 as compared with NV10 or TRAIL alone. These results suggest that the size of NPs is important when TRAIL is vectorized for cancer therapy.

Silver nanoparticles (Ag NPs) have been used widely for antibacterial applications; however, the effects of their sizes on antibacterial activities and toxicities to human cells, particularly for the laser-generated Ag NPs, are not fully understood. In this study, sucrose gradient centrifugation was used to separate laser-generated Ag NPs into different fractions by size. Transmission electron microscopy was used to analyze the size distribution of the Ag NPs, and well diffusion method was used to evaluate the antibacterial activity of the Ag NP fractions against the Escherichia coli. Results showed that the antibacterial effects of laser-generated Ag NPs inversely correlated to the particle size. Among Ag NP fractions with average sizes ranging 19–47 nm, the 19-nm Ag NPs presented the highest bactericidal effect. The smaller sized laser Ag NPs also significantly induced the generation of reactive oxygen species when applied to E. coli, compared with that of the larger sized laser Ag NPs. Cytotoxicity analysis revealed that the different sized laser-generated Ag NPs were not significantly toxic to the human fibroblasts and lung epithelial cells in a 72-h in vitro cell culture period. Understanding the size-dependent functional properties of the laser-generated Ag NPs helps informing the designs for future applications of the laser-generated Ag NPs.

The structural, microstructural, and magnetic properties of ~5-nm-sized Co_0.6Zn_0.4Fe_2 − xGd_xO₄ nanoparticles were investigated in order to evaluate their capability to enhance the magnetic resonance imaging contrast as high magnetization agents. A focus was made on the solubility of Gd³⁺ cations within the spinel lattice. By coupling X-ray diffraction to X-ray fluorescence spectroscopy, we demonstrated that only a limited fraction of Gd³⁺ can substitute Fe³⁺ ions into the whole crystal structure and does not exceed 6 at.-%. At this concentration, the room temperature (27°C) saturation magnetizations of the prepared superparamagnetic nanocrystals were found to be close to 80 emu g⁻¹. Coating these nanoparticles with hydrophilic dopamine ligands leads to the formation of ~50-nm-sized clusters in water. As a consequence, relatively high r₂/r₁ ratios of transverse to longitudinal proton relaxivities and high r₂ values were measured in the resulting colloids at physiological temperature (37°C) for an applied magnetic field of 1.41 T: 33 and 188 mM⁻¹ sec⁻¹, respectively, for the richest system in gadolinium. Moreover, after incubation with healthy human model cells (fibroblasts) at doses as high as 10 μg mL⁻¹, they induce neither cellular death nor acute cellular damage making the engineered probes particularly valuable for negative magnetic resonance imaging contrasting.

Cationic and highly branched poly (trimethylphosphonium ethylacrylate-co-poly (ethylene glycol) acrylate) (p (TMPEA-co-PEGA)), and its ammonium equivalent, have been synthesised from post-polymerisation modification of a poly (bromo ethylacrylate-co-poly (ethylene glycol) acrylate) (p (BEA-co-PEGA)) precursor polymer produced using reversible addition fragmentation chain transfer (RAFT) polymerisation. The cationic polymers were evaluated for their ability to complex nucleic acids, their in vitro cytotoxicity and their GFP pDNA transfection efficiency. The results show RAFT copolymerisation of BEA and PEGA is a simple route to polyphosphoniums showing reduced cytotoxicities and higher transfection efficiencies than their polyammonium alternatives.

Pharmaceutical quality by design (QbD) is a systematic approach to drug development that begins with predefined objectives and emphasises product and process understanding and control based on sound science and quality risk management. First and foremost, QbD is an experimental design philosophy, which emphasises the value of thorough intellectual planning prior to the commencement of laboratory studies. Academic researchers whose ambitions lie in translational science may benefit from the lessons learned by the pharmaceutical industry following implementation of QbD into their development philosophy. However, because of the very interdisciplinary nature of academic nanomedicine research, it is likely that very few investigators are aware of QbD and how aspects of it may be judiciously implemented in an academic research setting. This review provides an introduction to the main elements of QbD and gives examples of case studies where QbD has been applied to nanomedicine research.

Ductal carcinoma in situ is the most commonly diagnosed early stage breast cancer. The efficacy of intraductally delivered poly(ethylene glycol)-doxorubicin (PEG-DOX) nanocarriers, composed of one or more DOX conjugated to various PEG polymers, was investigated in an orthotopic ductal carcinoma in situ-like rat model. In vitro cytotoxicity was evaluated against 13762 Mat B III cells using MTT assay. The orthotopic model was developed by inoculating cancer cells into mammary ducts of female Fischer 344 retired breeder rats. The ductal retention and in vivo antitumour efficacy of two of the six nanocarriers (5 kDa PEG-DOX and 40 kDa PEG-(DOX)₄) were investigated based on in vitro results. Mammary retention of DOX and PEG-DOX nanocarriers was quantified using in vivo imaging. Histopathologic effects of DOX and PEG-DOX nanocarriers on mammary ductal structure were also investigated. Cytotoxicities of small linear PEG-DOX nanocarriers (5 and 10 kDa) were not different from DOX whereas larger PEG-DOX nanocarriers showed reduced potency. The order of mammary retention was 40 kDa PEG-(DOX)₄ > 5 kDa PEG-DOX >> DOX, in normal and tumour-bearing rats. Intraductally administered PEG-DOX nanocarriers and DOX were effective in reducing tumour incidence and increasing survival rate, with no significant differences found among the three treatment groups. However, nanocarriers administered intravenously at the same doses were not effective, and intraductally administered free DOX caused severe local toxicity. Intraductal administration of PEG-DOX nanocarriers is effective and less toxic than that of free DOX, as well as IV DOX/PEG-DOX. Furthermore, PEG-DOX nanocarriers demonstrate the added benefit of prolonging DOX ductal retention, which would necessitate less frequent dosing.