Responses of bimetallic Ag/ZnO alloy nanoparticles and urea on morphological and physiological attributes of wheat.

Wheat (Triticum aestivum L.) is the most important staple food crop globally. According to economic survey 2018-19, agriculture sector of Pakistan grew by 0.85%, with wheat accounting for 8.9% of agriculture and 1.6% of GDP, and its production fell short of the target by 4.9%. Wheat requires beneficial ties to improve its efficiency with the help of modern technology. Nanotechnology modifies conventional agricultural practices as these are stimulating agents for plant growth. Green bimetallic Ag/ZnO alloy nanoparticles (NPs) synthesised from salts reduced by Moringa oleifera and characterised by UV-visible spectroscopy, scanning electron microscopy, and energy-dispersive X-ray spectroscopy are studied herein. Different concentrations of urea and Ag/ZnO alloy NPs were applied exogenously to wheat plants (Pakistan-13 and Galaxy13). A significant effect of 100 mg/L urea and 75 ppm Ag/ZnO alloy NPs was observed on the morphology of wheat, with a maximum increase of 58% plant length, 85% leaf area, 89% plant fresh weight and 76% plant dried weight. In physiological parameters, relative water content and membrane stability index have shown maximum increases of 39% and 77%, while chlorophyll a, b, and total chlorophyll content (TCC) showed maximum increases of 92%, 71%, and 84% respectively. Evidence of the morpho-physiological responses of urea and green synthesised alloy NPs on wheat varieties are reported on.

Transdermal delivery of rapamycin with poor water-solubility by dissolving polymeric microneedles for anti-angiogenesis.

Angiogenesis plays an important role in the occurrence and development of skin tumors and vascular anomalies (VAs). Many drugs have been adopted for the inhibition of angiogenesis, among which rapamycin (RAPA) possesses good application prospects. However, the clinical potential of RAPA for VAs is limited by its poor solubility, low bioavailability, and high cytotoxicity. To extend its application prospect for VAs treatment, in this study, we develop RAPA-loaded dissolving polymeric microneedles (RAPA DMNs) made of polyvinylpyrrolidone (PVP) due to its excellent solubilizing ability. RAPA DMNs are shown to have sufficient mechanical strength to overcome the skin barrier of the stratum corneum and could deliver RAPA to a depth of 200 µm. The microneedle shafts completely dissolve and 80% of the drug could be released within 10 min after insertion ex vivo. The DMNs-penetrated mice skin could repair itself within 4 h after the application of RAPA DMNs. RAPA DMNs also show good anti-angiogenic effect by inhibiting the growth of human umbilical vein endothelial cells (HUVECs) and decreasing the secretion of vascular endothelial growth factor (VEGF). Therefore, RAPA DMNs promisingly provide a safe and efficient approach for VAs treatment.

Polyethylenimine Hybrid Thin-Shell Hollow Mesoporous Silica Nanoparticles as Vaccine Self-Adjuvants for Cancer Immunotherapy.

Conventional adjuvants (e.g., aluminum) are insufficient to trigger cell-mediated immunity, which plays a crucial role in triggering specific immunity against cancer. Therefore, developing appropriate adjuvants for cancer vaccines is a central way to stimulate the antitumor immune response. Hollow mesoporous silica nanoparticles (HMSNs) have been proven to stimulate Th1 antitumor immunity in vivo and promote immunological memory in the formulation of novel cancer vaccines. Yet, immune response rates of existing HMSNs for anticancer immunity still remain low. Here, we demonstrate the generation of polyethylenimine (PEI)-incorporated thin-shell HMSNs (THMSNs) through a facile PEI etching strategy for cancer immunotherapy. Interestingly, incorporation of PEI and thin-shell hollow structures of THMSNs not only improved the antigen-loading efficacy and sustained drug release profiles but also enhanced the phagocytosis efficiency by dendritic cells (DCs), enabled DC maturation and Th1 immunity, and sustained immunological memory, resulting in the enhancement of the adjuvant effect of THMSNs. Moreover, THMSNs vaccines without significant side effects can significantly reduce the potentiality of tumor growth and metastasis in tumor challenge and rechallenge models, respectively. THMSNs are considered to be promising vehicles and excellent adjuvants for the formulation of cancer vaccines for immunotherapy.

Biodegradable Polymer Microparticles with Tunable Shapes and Surface Textures for Enhancement of Dendritic Cell Maturation.

In this report, we present a facile approach to produce biodegradable polymeric microparticles with uniform sizes and controllable morphologies by blending hydrophobic poly(d, l-lactic-co-glycolide) (PLGA) and amphiphilic poly(d, l-lactic acid)-b-poly(ethylene glycol) (PLA-b-PEG) in a microfluidic chip. Microparticles with tentacular, hollow hemispherical, and Janus structures were obtained after complete evaporation of the organic solvent by manipulating the interfacial behavior of emulsion droplets and the phase separation behavior inside the droplets. The number and length of the tentacles on the surface of tentacular microparticles could be tailored by varying the initial concentration and blending ratios of the polymers. The organic solvent played an important role in controlling the morphologies of microparticles. For example, blending PLA16k-b-PEG5k with PLGA100k in dichloromethane resulted in tentacular microparticles, whereas hollow hemispherical microparticles were obtained in trichloromethane. Moreover, these microparticles with controllable shapes and surface textures have significant influence on the immune response of dendritic cells (DCs), showing a morphology-dependent enhancement of DC maturation.

Liposomes-coated gold nanocages with antigens and adjuvants targeted delivery to dendritic cells for enhancing antitumor immune response.

For nanovaccine-based cancer immunotherapy, dendritic cells (DCs) are one of the most powerful antigen presenting cells (APCs) that initiate and promote the maturation of antigen-specific cytotoxic T lymphocytes (e.g., CD8+ T cells) to induce the local and systemic antitumor immunity and further suppress the tumor metastasis and produce long-term protection against tumor. Thus, the activation and maturation of DCs is the prerequisite for efficient CD8+ T cell-based antitumor immune responses, which is considered as a primary and promising task for nanovaccine engineering. Herein, we introduce a versatile nanovaccine of liposomes-coated gold nanocages (Lipos-AuNCs) modified with DCs specific antibody aCD11c for targeted delivery of adjuvant MPLA and melanoma antigen peptide TRP2 to promote the activation and maturation of DCs, and enhance tumor specific T lymphocytes responses. Moreover, AuNCs accumulation and AuNCs-engulfed DCs migration to regional lymph nodes (RLNs) became real-time visualization through in vivo fluorescence and photoacoustic (PA) imaging to monitor the immunity process. In vivo experimental results demonstrated that the targeted antigen/adjuvants-loaded AuNCs exhibited enhanced antitumor immune response to inhibit tumor growth and metastasis in both B16-F10 prophylactic and lung metastasis models, which may act as a promising nanoplatform for antitumor immunotherapy and in vivo tracking.