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Nanomaterials, especially graphene derivatives, have become major tools in the biomedical area. Understanding the way that graphene interacts with component elements of biological systems, like biological membranes, is critical for the development of successful biomedical applications. The interaction mechanism of graphene sheets with a model cell membrane was investigated in this study using molecular dynamics (MD) simulations under three different conditions: pristine graphene (PG), carboxyl group-functionalized graphene (G-COOH), and amine group-functionalized graphene (G-NH2). The MD simulations demonstrated that functional groups on graphene surfaces improve their interaction with the head groups of the membrane. In 200 nanoseconds, PG reached equilibrium outside and near the phospholipid membrane. G-NH2 was positioned away from the model membrane’s surface, while G-COOH and G-NH2 also achieved equilibrium outside the membrane. It was shown by molecular dynamics simulations that after 200 ns, all three systems had attained their stable states. Crucially, it is discovered that the kind of functional groups greatly affected how the nanoparticles and membrane interacted. Each and every nanocarrier has a strong propensity to break through the membrane. The van der Waals interaction energies for the PG, G-NH2, and G-COOH systems were further shown by the obtained data to be roughly −400.66, −397.52, and −876.36 kJ/mol, respectively. These results support the notion that G-COOH interacts with the model cell bilayer more strongly than PG and G-NH2. This work highlights the influence of functional groups on the interaction of graphene sheets with biological membranes, offering important insights into the equilibrium behavior and entry mechanism of graphene sheets in a model cell membrane.

Alzheimer's disease is characterized by a combination of several neuropathological hallmarks, such as extracellular aggregates of beta amyloid (Aβ). Numerous alternatives have been studied for inhibiting Aβ aggregation but, at this time, there are no effective treatments available. Here, we developed the tri-component nanohybrid system AuNPs@POM@PEG based on gold nanoparticles (AuNPs) covered with polyoxometalates (POMs) and polyethylene glycol (PEG). In this work, AuNPs@POM@PEG demonstrated the inhibition of the formation of amyloid fibrils, showing a 75% decrease in Aβ aggregation in vitro. As it is a potential candidate for the treatment of Alzheimer's disease, we evaluated the cytotoxicity of AuNPs@POM@PEG and its ability to cross the blood–brain barrier (BBB). We achieved a stable nanosystem that is non-cytotoxic below 2.5 nM to human neurovascular cells. The brain permeability of AuNPs@POM@PEG was analyzed in an in vitro microphysiological model of the BBB (BBB-on-a-chip), containing 3D human neurovascular cell co-cultures and microfluidics. The results show that AuNPs@POM@PEG was able to cross the brain endothelial barrier in the chip and demonstrated that POM does not affect the barrier integrity, giving the green light to further studies into this system as a nanotherapeutic. [ABSTRACT FROM AUTHOR]

The regulation of tumor immunosuppressive microenvironments via precise drug delivery is a promising strategy for preventing tumor recurrence and metastasis. Inspired by the stealth strategy, a stealthy nanovehicle based on neutrophil camouflage is developed to achieve precise delivery and tumor immunotherapy by triggering pyroptosis. The nanovehicle comprises anti‐CD11b‐ and IR820‐conjugated bovine serum albumin nanoparticles loaded with decitabine. Camouflaged by neutrophils, the nanovehicles achieve efficient tumor delivery by neutrophil hitchhiking owing to the biotropism of neutrophils for tumors. The fluorescent signal molecule, IR820, on the nanovehicle acts as a navigation monitor to track the precise delivery of the nanovehicle. The released decitabine upregulates gasdermin E, and laser irradiation activates caspase‐3, thereby resulting in pyroptosis, which improves the system's adaptive immune response. In a triple‐negative breast cancer animal model, it regulates the immunosuppressive microenvironment for effective tumor immunotherapy and induces a long‐lasting and strong immune memory to prevent lung metastasis. [ABSTRACT FROM AUTHOR]

Although solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have been successfully used as drug delivery systems for about 30 years, the usage of these nanoparticles as food-grade nanovehicles for nutraceuticals or bioactive compounds has been, relatively speaking, scarcely investigated. With fast-increasing interest in the incorporation of a wide range of bioactives in food formulations, as well as health awareness of consumers, there has been a renewed urge for the development of food-compatible SLNs and/or NLCs as nanovehicles for improving water dispersibility, stability, bioavailability, and bioactivities of many lipophilic nutraceuticals or poorly soluble bioactives. In this review, the development of food-grade SLNs and NLCs, as well as their utilization as nanosized delivery systems for lipophilic or hydrophobic nutraceuticals, was comprehensively reviewed. First, the structural composition and preparation methods of food-grade SLNs and NLCs were simply summarized. Next, some key issues about the usage of such nanoparticles as oral nanovehicles, e.g., incorporation and release of bioactives, oxidative stability, lipid digestion and absorption, and intestinal transport, were critically discussed. Then, recent advances in the utilization of SLNs and NLCs as nanovehicles for encapsulation and delivery of different liposoluble or poorly soluble nutraceuticals or bioactives were comprehensively reviewed. The performance of such nanoparticles as nanovehicles for improving stability, bioavailability, and bioactivities of curcuminoids (and curcumin in particular) was also highlighted. Lastly, some strategies to improve the oral bioavailability and delivery of loaded nutraceuticals in such nanoparticles were presented. The review will be relevant, providing state-of-the-art knowledge about the development of food-grade lipid-based nanovehicles for improving the stability and bioavailability of many nutraceuticals. [ABSTRACT FROM AUTHOR]

BACKGROUND: The formulation of phytosterol (PS)‐enriched functional foods has attracted increasing interest in the recent years, owing to its potential health effects. However, the poor solubility and bioavailability greatly limit PS application in this regard. This study investigated whether soy protein isolate (SPI) could effectively perform as a nanocarrier for improving the water solubility, bioaccessibility, and cholesterol‐lowering activity of PSs. RESULTS: In this work, we fabricated SPI–PS nanocomplexes, which not only can enhance the stability and bioaccessibility of PS, but also improve the cholesterol‐lowering ability of SPI. This improvement was mainly due to the formation of protein‐active substance complexes, through hydrophobic interactions. The complexation with PSs resulted in formation of nanosized particles with greater sizes, lower ζ‐potential, and higher surface hydrophobicity. The encapsulation efficiency, loading amount, and solubility of PS were closely related to the applied PS concentration in the mixed dispersions, and the maximal PS solubility in the aqueous phase reached about 1.63 mg mL−1 at the highest PS concentration (2.0 mg mL−1). The PS molecules in the nanocomplexes were mainly present in the amorphous form. The enhanced in vitro cholesterol‐lowering activity of PS nanocomplexes relative to free PS seemed to be closely related to its higher bioaccessibility. CONCLUSION: The findings are of relevance for the development of food‐grade PS ingredients suitable for the formulations of PS‐enriched functional foods. © 2022 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

One of the main challenges of transmucosal drug delivery is that of enabling particles and molecules to move across the mucosal barrier of the mucosal epithelial surface. Inspired by nanovehicles and mucus-penetrating nanoparticles, a magnetically driven, mucus-inert Janus-type nanovehicle (Janus-MMSN-pCB) was fabricated by coating the zwitterionic polymer poly(carboxybetaine methacrylate) (pCB) on the mesoporous silica nanorod, which was grown on one side of superparamagnetic Fe3O4 nanoparticle using the sol–gel method. X-ray diffraction, transmission electron microscopy, vibrating sample magnetometry, and Fourier infrared spectroscopy were used to characterize the structure and morphology of the nanovehicles, proving the success of each synthesis step. The in vitro cell viability assessment of these composites using Calu-3 cell lines indicates that the nanovehicles are biocompatible in nature. Furthermore, the multiparticle tracking, Transwell® system, and cell imaging experimental results demonstrate that both the modification of pCB and the application of a magnetic field effectively accelerated the diffusion of the nanovehicles in the mucus and improved the endocytosis through Calu-3. The favorable cell uptake performance of Janus-MMSN-pCB in mucus systems with/without magnetic driving proves its potential role in the diagnosis, treatment, and imaging of mucosal-related diseases. [ABSTRACT FROM AUTHOR]

The poor water solubility and inadequate oral bioavailability of gefitinib (Gef) remain a critical issue to achieve the therapeutic outcomes. Herein, we designed a poly(maleic anhydride-alt-1-octadecene) (PMA/C18) based lipid nanovehicle (PLN) to improve the intestinal absorption and oral bioavailability of poorly water-soluble Gef. PLN was nanometer-sized particles, and Gef was dispersed in the PLN formulation as amorphous or molecular state. At 4 h of oral administration, the tissue concentration of Gef in duodenum, jejunum, and ileum was profoundly enhanced 3.37-, 8.94-, and 8.09-fold by PLN when comparing to the counterpart lipid nanovehicle. Moreover, the oral bioavailability of Gef was significantly enhanced 2.48-fold by the PLN formulation when comparing to the free drug suspension. Therefore, this study provides an encouraging bioadhesive delivery platform to improve the oral delivery of poorly water-soluble drugs. [ABSTRACT FROM AUTHOR]

The regulation of immunosuppressive microenvironments in tumors through targeted drug delivery shows promise for immunochemotherapy in bladder cancer. Drawing inspiration from stealth tactics, a nano-vehicle camouflaged with platelets (PLTs) was developed to enable precise delivery and trigger pyroptosis for tumor immunotherapy. Methods: Erdafitinib (Erda) was nano-sized and encapsulated in PLTs to construct nano-Erda@PLT. Characterization of the PLTs camouflaged nano-vehicle was conducted using Zetasizer, SEM, and confocal laser scanning microscopy. The excellent targeted delivery property of the PLTs nano-vehicle was investigated through intravital imaging, three-dimensional microspheres, and SEM. Validation of pyroptosis in bladder cancer cells via the caspase-3/GSDME pathway was performed using western blot, immunofluorescence, and ELISA tests. Immunotherapy by nano-Erda@PLT treatment in vivo was confirmed using H&E, immunohistochemical, and flow cytometry. Lastly, the side effects of nano-Erda@PLT were assessed. Results: Proteomic analysis revealed that the activation of p-selectin on platelets facilitated the identification of nano-Erda@PLT targeted therapies. Nanoscale of Erda released in response to adenosine diphosphate, facilitated intratumoral permeation. This could contribute to an upregulation of the key proteins of pyroptosis, caspase-3 and GSDME, in bladder cancer cells due to nano-Erda@PLT accumulation. Additionally, the burst release of numerous inflammatory factors may enhance the system's adaptive immune response. In a bladder cancer animal model, this treatment was found to regulate the immunosuppressive microenvironment, resulting in effective tumor immunotherapy and the induction of a long-lasting, robust immune memory. Conclusion: PLTs-camouflaged nano-vehicles enable nano-Erda-mediated tumor immunotherapy through the induction of pyroptosis. These findings introduce a novel approach in exploring nanomaterial-mediated pyroptosis for cancer immunotherapy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Although solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have been successfully used as drug delivery systems for about 30 years, the usage of these nanoparticles as food-grade nanovehicles for nutraceuticals or bioactive compounds has been, relatively speaking, scarcely investigated. With fast-increasing interest in the incorporation of a wide range of bioactives in food formulations, as well as health awareness of consumers, there has been a renewed urge for the development of food-compatible SLNs and/or NLCs as nanovehicles for improving water dispersibility, stability, bioavailability, and bioactivities of many lipophilic nutraceuticals or poorly soluble bioactives. In this review, the development of food-grade SLNs and NLCs, as well as their utilization as nanosized delivery systems for lipophilic or hydrophobic nutraceuticals, was comprehensively reviewed. First, the structural composition and preparation methods of food-grade SLNs and NLCs were simply summarized. Next, some key issues about the usage of such nanoparticles as oral nanovehicles, e.g., incorporation and release of bioactives, oxidative stability, lipid digestion and absorption, and intestinal transport, were critically discussed. Then, recent advances in the utilization of SLNs and NLCs as nanovehicles for encapsulation and delivery of different liposoluble or poorly soluble nutraceuticals or bioactives were comprehensively reviewed. The performance of such nanoparticles as nanovehicles for improving stability, bioavailability, and bioactivities of curcuminoids (and curcumin in particular) was also highlighted. Lastly, some strategies to improve the oral bioavailability and delivery of loaded nutraceuticals in such nanoparticles were presented. The review will be relevant, providing state-of-the-art knowledge about the development of food-grade lipid-based nanovehicles for improving the stability and bioavailability of many nutraceuticals.

Oral chemotherapy offers a more convenient treatment option for cancer patients but the effectiveness is significantly hindered by the limited drug delivery efficiency. Herein, we designed legumain-activable melittin (LM) decorated polymeric nanovehicles loading IR-780 and sorafenib (LPN) to enhance their oral delivery to tumors, with efficient accumulation and penetration capacity, for combinational photothermal-chemotherapy of gastric cancer. The nanosized LPN displayed good stability in simulated gastrointestinal fluids. After oral administration, the oral bioavailability of sorafenib was remarkably improved (75.9-fold by LPN versus free drug suspension). Moreover, the orally administered LPN could preferentially accumulate at the tumor site and penetrate into the interior regions of the tumor mass. Upon combination with laser irradiation, LPN produced notable inhibition of tumor growth, which was more effective than the counterpart unmodified nanovehicles. Therefore, LPN represents an encouraging oral delivery nanoplatform with favorable tumor accumulation and penetration capability for oral combinational cancer therapy. Unlabelled Image • Legumain-activable melittin decorated polymeric nanovehicles (LPN) improve the oral delivery of water-insoluble sorafenib. • Orally administered LPN preferentially accumulates at the tumor site with deep penetrating capacity. • Upon combination with laser irradiation, LPN produced notable inhibition of tumor growth versus counterpart nanovehicles. • LPN represents an encouraging oral delivery nanoplatform for oral combinational cancer therapy. [ABSTRACT FROM AUTHOR]

Though early detection and treatment of primary tumors has significantly improved in recent years, metastatic disease remains among the most significant challenges in cancer therapy. Cancer cells can disseminate before the primary tumor is detected to form micro or gross metastases, requiring toxic systemic therapies. To prevent and suppress metastases, we have developed a nontoxic, long-circulating nanoscale coordination polymer (NCP) protecting microRNA (miRNA) in circulation and releasing it in tumors. PtIV(en) 2 [en = ethylenediamine] containing NCPs (PtEN) can release a nontoxic, kinetically inert PtII(en) 2 compound and carbon dioxide which aids the endosomal escape of its miRNA cargo, miR-655-3p. Without the presence of the PtEN core, the miRNA showed cellular uptake but no effect. When transfected into human colorectal HCT116 cells by NCPs, this oligometastatic miRNA limited proliferation and epithelial-to-mesenchymal transition by preventing β-catenin nuclear translocation and tumor cell invasion. Systemic administrations of PtEN/miR-655-3p sustained effective transfection to reduce liver colonization and tumor burden in a xenogenic hepatic metastatic model of HCT116 without any observable toxicity. Image 1 [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Graphene oxide (GO), as a drug delivery carrier, has attracted considerable attention because of its interesting properties. However, GO tends to aggregate in aqueous solution. Amphiphilic molecules are usually necessary to stabilize GO. The introduction of these non-functional macromolecules on the one hand reduces drug loading, but on the other hand may cause unpredictable side effects. This study proposes a new strategy for stabilizing GO with a functional photothermal agent, IR820 (new indocyanine green) derivative. IR820 derivative results from the conjugation of active targeted lactobionic acid (LA) with IR820 for the formation of IR820-LA. IR820-LA features central aromatic groups that can associate with the GO basal plane through π-π interactions. The flanking moiety of hydrophilic LA and sulfonic groups thus provides steric stabilization of GO in aqueous solution. Moreover, IR820-LA endows GO/doxorubicin (GO/DOX) nanovehicles with fluorescence imaging ability and actively targeted chemo-photothermal therapy. Experimental results both in vitro and in vivo have indicated its good chemo-photothermal therapeutic effect according to its active tumor targeting ability and pH-sensitive drug release characteristics. Therefore, our GO/DOX/IR820-LA nanohybrids can be excellent nanoplatforms for active tumor-targeted chemo-photothermal therapy with imaging guidance. [ABSTRACT FROM AUTHOR]

Abstract Soy proteins as an important food ingredient have been widely applied in food formulations, due to their good nutritional value, high functionalities, and health-benefiting effects. Evidences have been fast accumulating to indicate that soy proteins are a kind of excellent building materials to be fabricated into a variety of nanostructured delivery systems for food bioactive ingredients. This review mainly presents the state-of-the-art knowledge about the fabrication of different kinds of nanostructures of soy proteins, as well as their applications to perform as nanocarriers for bioactives, achieved during the past decade. The composition, structure and physicochemical properties of soy proteins (including glycinin, β -conglycinin, and soy protein isolate) are first summarized. Then, the main strategies and techniques to fabricate a variety of nanostructured soy proteins are reviewed, including heat-induced aggregation, complexation with polysaccharides, emulsification-evaporatioin, desolvation/solvent displacement, crosslinking, self-assembly, electrospraying, nanoemulsions and interfacially nanostructured emulsions. Lastly, the feasibility of these nanostructured soy proteins (especially nanoparticles) to peroform as effective nanocarriers or delivery systems for bioactives are discussed. Due to the fast increasing interest of the food industry and consumer health awareness for the incorporation of soy proteins in functional food formulations, this review is of importance for guiding the development of novel 'dual-function' nanostructured soy protein-bioactive formulations. Graphical abstract Nanostructured Soy Proteins: Fabrication and Applications as Delivery Systems for Bioactives. Image 1016 Highlights • Soy proteins exhibit a great potential to be fabricated into a variety of nanostructures. • Soy protein nanoparticles can be fabricated via a number of strategies. • Nanostructured soy proteins can perform as effective delivery systems for bioactives. • Novel 'dual-function' nanostructured soy protein-bioactive formulations can be produced. • More efforts are still needed to demonstrate the effectiveness of these delivery systems. [ABSTRACT FROM AUTHOR]

In this work, the effect of egg white protein (EWP) concentration on linoeic acid (LA) binding capacity and particle size of heat-induced EWP nanovehicles (EWPn) was studied. Two heat treatment were applied at the following conditions: i) 80 °C, 10 min, pH 10.8, varying protein concentration between 0.85 and 3.41 % wt. and ii) 80 °C, 5 min, pH 11.4, varying protein concentration between 0.85 and 4.26 % wt. Turbidity and LA binding capacity were measured using absorbance at 400 nm. LA was taken as a model lipophilic compound. Particle size analysis was performed by means of DLS. Results indicated that both turbidity and average particle diameter (Z-Ave) increased linearly with protein concentration; although there is no clear tendency in volume based particle size distributions (PSDv). Particle size results indicated that nanosized particles (<100 nm) were obtained for both treatments (i and ii). Moreover, protein concentration had a negligible effect on LA binding capacity of EWPn. Finally, EWPn obtained at 80 °C, 5 min, pH 11.4 and 3.41 % wt. protein, were spray dried, obtaining a white fine powder (8.72 ± 0.13% moisture content). In general, PSDv and LA binding capacity of EWPn did not change after spray drying. Remarkably, results suggest that EWPn can be obtained by a simple process (involving dilution, centrifugation, pH adjustment, heat treatment and, optionally, spray drying) using egg white as a commercially available raw material. [ABSTRACT FROM AUTHOR]

In the present work, nanovehicles for hydrophobic compounds were obtained by controlled heat treatment of commercial egg white protein (EWP) dispersions. The effect of heating time (0–20 min) and solution pH (9.6–11.4) on particle size, surface hydrophobicity and binding capacity for a model hydrophobic compound, linoleic acid (LA), was evaluated. Correlations between process variables and structural parameters were made, in order to understand EWP nanovehicles functionality. In general, a decrease in particle size was observed with the increase in pH, which was attributed to a predominance of electrostatic repulsions between protein anionic charges. EWP nanovehicles showed higher surface hydrophobicity values in comparison with native EWP; however, no clear influence of heating time and solution pH was evidenced. On the other hand, the increase in pH increased the nanovehicles LA binding capacity. A strong positive linear correlation (R > 0.9) was observed between surface area/volume (A/V) for EWP nanovehicles (assuming spherical form) and solution pH. A strong positive correlation was also observed between A/V and LA binding capacity. Information derived from this work could be of practical interest for hydrophobic bioactive compound vehiculization. [ABSTRACT FROM AUTHOR]

In this study, we report a facile method to construct a bioactive (poly(phenylalanine)- b -poly( l -histidine)- b -poly(ethylene glycol) polypeptide nanoconstruct to co-load doxorubicin (DOX) and quercetin (QUR) (DQ-NV). The smart pH-sensitive nanovehicle was fabricated with precisely tailored drug-to-carrier ratio that resulted in accelerated, sequential drug release. As a result of ratiometric loading, QUR could significantly enhance the cytotoxic potential of DOX, induced marked cell apoptosis; change cell cycle patterns, inhibit the migratory capacity of sensitive and resistant cancer cells. In particular, pro-oxidant QUR from DQ-NV remarkably reduced the GSH/GSSG ratio, indicating high oxidative stress and damage to cellular components. DQ-NV induced tumor shrinkage more effectively than the single drugs in mice carrying subcutaneous SCC-7 xenografts. DQ-NV consistently induced high expression of caspase-3 and PARP and low expression of Ki67 and CD31 immunomarkers. In summary, we demonstrate the development of a robust polypeptide-based intracellular nanovehicle for synergistic delivery of DOX/QUR in cancer chemotherapy. Statement of Significance In this study, we report a facile method to construct bioactive and biodegradable polypeptide nanovehicles as an advanced platform technology for application in cancer therapy. We designed a robust (poly(phenylalanine)- b -poly( l -histidine)- b -poly(ethylene glycol) nanoconstruct to co-load doxorubicin (DOX) and quercetin (QUR) (DQ-NV). The conformational changes of the histidine block at tumor pH resulted in accelerated, sequential drug release. QUR could significantly enhance the cytotoxic potential of DOX, induce marked cell apoptosis, change cell cycle patterns, and inhibit the migratory capacity of sensitive and resistant cancer cells. DQ-NV induced tumor shrinkage more effectively than the single drugs and the 2-drug cocktail in tumor xenografts . In summary, we demonstrate the development of an intracellular nanovehicle for synergistic delivery of DOX/QUR in cancer chemotherapy. [ABSTRACT FROM AUTHOR]

Highlights: [•] Hyperbranched amylopectin derivatives were synthesized through a one-step reaction. [•] They consisted of hydrophobic shells and large hydrophilic cores. [•] Their weight molecular weights were extremely high. [•] They exhibited high encapsulation capabilities toward water-soluble molecules. [•] They could be used as functional nanovehicles. [ABSTRACT FROM AUTHOR]

Abstract: Curcumin is an antioxidant and anti-inflammatory bioflavonoid that has been recently identified as an anti-amyloid agent as well. To make it more available in its potent form as a potential amyloid disaggregation agent, we employed high-density lipoproteins (HDL), which are lipid–protein complexes that transport plasma cholesterol, to transport curcumin. The objective of this study was to employ reconstituted HDL containing human apoE3 N-terminal (NT) domain, as a vehicle to transport curcumin. The NT domain serves as a ligand to mediate binding and uptake of lipoprotein complexes via the low-density lipoprotein receptor (LDLr) family of proteins located at the cell surface. Reconstituted HDL was prepared with phospholipids and recombinant apoE3-NT domain in the absence or presence of curcumin. Non-denaturing polyacrylamide gel electrophoresis indicated that the molecular mass and Stokes'' diameter of HDL bearing curcumin were ~670kDa and ~17nm, respectively, while electron microscopy revealed the presence of discoidal particles. Fluorescence emission spectra of HDL bearing (the intrinsically fluorescent) curcumin indicated that the wavelength of maximal fluorescence emission (λmax) of curcumin was ~495nm, which is highly blue-shifted compared to λmax of curcumin in solvents of varying polarity (λmax ranging from 515–575nm) or in aqueous buffers. In addition, an enormous enhancement in fluorescence emission intensity was noted in curcumin-containing HDL compared to curcumin in aqueous buffers. Curcumin fluorescence emission was quenched to a significant extent by lipid-based quenchers but not by aqueous quenchers. These observations indicate that curcumin has partitioned efficiently into the hydrophobic milieu of the phospholipid bilayer of HDL. Functional assays indicated that the LDLr-binding ability of curcumin-containing HDL with apoE3-NT is similar to that of HDL without curcumin. Taken together, we report that apoE-containing HDL has a tremendous potential as a ‘nanovehicle’ with a homing device to transport curcumin to target sites. [Copyright &y& Elsevier]

Abstract: Delivery of poorly soluble drugs has been problematic due to its low absorption profile and bioavailability. In this work, ursodeoxycholic acid (UDCA), a poorly-soluble drug, was intercalated into inorganic nanovehicle, layered double hydroxides (LDHs), with a molecular level to enhance its solubility in biological fluid. The UDCA-loaded nanovehicle (i.e., UDCA-LDHs) was also coated with an anionic polymer, Eudragit® S100, to increase the dissolution rate of UDCA. According to the powder X-ray diffraction (PXRD) patterns of UDCA-LDHs, the gallery height of LDHs was expanded from 3.6Å to 28.3Å, indicating that the UDCA molecules were successfully intercalated into the interlayer space of LDHs. Fourier transform infrared (FT-IR) spectra also revealed that the UDCA molecules were well stabilized in the LDHs through electrostatic interaction. The in vitro dissolution test in a simulated biological fluid (pH=6.8) showed that the total dissolved fraction of UDCA for the first 2h was about 60.2% for the Eudragit® S100 coated UDCA-LDHs, which was a dramatic increase as compared with 19.0% dissolution from intact UDCA. It is, therefore, concluded that LDHs nanovehicle coated with an anionic polymer is a promising delivery system for improving aqueous solubility of poorly soluble drugs. [ABSTRACT FROM AUTHOR]

Abstract: Zwitterionic diazeniumdiolate, a nitric oxide precursor, was dissolved in basic buffer solution (pH=9.0) and encapsulated in thermo-sensitive liposomes composed of phospholipids of different sensitive temperatures. The basic intra-liposomal environment dramatically delayed spontaneous NO release. When the liposomes were placed in physiological buffer solution and temperatures were increased to the sensitive temperatures of the phospholipids’ membranes, extra-liposomal protons started to influx to collapse the pH gradient and subsequently induce a significant NO release. Moreover, the presence of a stronger pH gradient when the liposomes were applied to a more acidic environment caused a higher proton influx driving force to trigger the influx of protons and, subsequently, NO release. In this work, we demonstrate that thermo-sensitive liposomes can be used to create a stable pH gradient in a nanoenvironment entrapping zwitterionic diazeniumdiolate for sustained and heat/acid-activated NO release. [Copyright &y& Elsevier]

This article provides an overview of principles and barriers relevant to intracellular drug and gene transport, accumulation and retention (collectively called as drug delivery) by means of nanovehicles (NV). The aim is to deliver a cargo to a particular intracellular site, if possible, to exert a local action. Some of the principles discussed in this article apply to noncolloidal drugs that are not permeable to the plasma membrane or to the blood–brain barrier. NV are defined as a wide range of nanosized particles leading to colloidal objects which are capable of entering cells and tissues and delivering a cargo intracelullarly. Different localization and targeting means are discussed. Limited discussion on pharmacokinetics and pharmacodynamics is also presented. NVs are contrasted to micro-delivery and current nanotechnologies which are already in commercial use. Newer developments in NV technologies are outlined and future applications are stressed. We also briefly review the existing modeling tools and approaches to quantitatively describe the behavior of targeted NV within the vascular and tumor compartments, an area of particular importance. While we list “elementary” phenomena related to different level of complexity of delivery to cancer, we also stress importance of multi-scale modeling and bottom-up systems biology approach. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:3518–3590, 2008 [ABSTRACT FROM AUTHOR]

Hypoxia is a critical cause of tumor immunosuppression, and it significantly limits the efficacy of many anticancer modalities. Herein, we report an amphiphilic F 11 -derivative-based oxygen-delivering polyfluorocarbon nanovehicle loading photodynamic DiIC 18 (5) and reactive oxygen species (ROS)-sensitive prodrug of chemo-immunomodulatory gemcitabine (PF 11 DG), aimed at relieving tumor hypoxia and boosting antitumor immunity for cancer therapy. We optimized F 11 -based polyfluorocarbon nanovehicles with a 10-fold enhancement of tumor oxygenation. PF 11 DG exhibited intriguing capabilities, such as oxygen-dissolving, ROS production, and responsive drug release. In tumors, PF 11 DG exhibited flexible intratumoral permeation and boosted robust antitumor immune responses upon laser irradiation. Notably, the treatment of PF 11 DG plus laser irradiation (PF 11 DG+L) significantly retarded the tumor growth with an 82.96% inhibition in the 4T1 breast cancer model and a 93.6% inhibition in the PANC02 pancreatic cancer model with better therapeutic benefits than non-oxygen-delivering nanovehicles. Therefore, this study presents an encouraging polyfluorocarbon nanovehicle with deep tumor-penetrating and hypoxia-relieving capacity to boost antitumor immunity for cancer treatment.

Visualizing siRNA delivery through medical imaging methods has drawn much attentions in recent gene therapy studies. Among them, iron oxide-based magnetic resonance imaging (MRI) is regarded as one of the most promising imaging modalities for its high spatial resolution as well as deep penetration and real-time properties. In this chapter, a detailed protocol of an amphiphilic superparamagnetic iron oxide (SPIO) nanovehicle-based siRNA delivery is described, mainly focusing on SPIO/siRNA complexes formation and characterization, in vitro and in vivo siRNA delivery, MRI study of the delivery and transfection efficiency evaluation.

The aim of this work is the preparation of an active nanovehicle for the effective administration of α-tocopheryl succinate (α-TOS). α-TOS is loaded in the core of nanoparticles (NPs) based on amphiphilic pseudo-block copolymers of N-vinyl pyrrolidone and a methacrylic derivative of α-TOS. These well-defined spherical NPs have sizes below 165 nm and high encapsulation efficiencies. In vitro activity of NPs is tested in hypopharynx squamous carcinoma (FaDu) cells and nonmalignant epithelial cells, demonstrating that the presence of additional α-TOS significantly enhances its antiproliferative activity; however, a range of selective concentrations is observed. These NPs induce apoptosis of FaDu cells by activating the mitochondria death pathway (via caspase-9). Both loaded and unloaded NPs act via complex II and produce high levels of reactive oxygen species that trigger apoptosis. Additionally, these NPs effectively suppress the vascular endothelial growth factor (VEGF) expression of human umbilical vein endothelial cells (HUVECs). These results open the possibility to use this promising nanoformulation as an α-TOS delivery system for the effective cancer treatment, effectively resolving the current limitations of free α-TOS administration., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The complexation of nanoparticles in unheated and heated (at 75-95°) soy protein isolate (SPI) with curcumin and the effects on curcumin stability/bioaccessibility and in vitro protein digestibility were investigated. The nanoparticles did not display noticeable changes in size and morphology upon nanocomplexation with curcumin, except their surface hydrophobicity. The encapsulation efficiency of curcumin progressively decreased with increasing initial curcumin concentration in the dispersion, while the load amount linearly increased. The solubility of curcumin in water was enhanced by the complexation above 98000-fold (vs free curcumin in water). The formation of the nanocomplexes considerably improved the storage stability of curcumin. In vitro simulated digestion experiments indicated that the complexation also improved the bioaccessibility of curcumin; the bioaccessibility was greatly impaired by hydrolysis-induced protein aggregation. Addtionally, the nanocomplexation significantly improved the in vitro protein digestibility of both unheated and heated SPI.

Multifunctional biocompatible nanomaterials containing both fluorescent and vehicle functions are highly favored in bioimaging, therapeutic, and drug delivery applications. Nevertheless, the rational design and synthesis of highly biocompatible multifunctional materials remain challenging. We present here the development of novel protein-gold hybrid nanocubes (PGHNs), which were assembled using gold nanoclusters, bovine serum albumin, and tryptophan as building blocks. The green-synthesized PGHNs in this study are blue-emitting under UV exposure and cube-shaped with a size of approximately 100 nm. These hybrid nanomaterials are highly biocompatible as shown by cytotoxicity experiments and can be readily internalized by different types of cells. Moreover, PGHNs can act as nanovehicles that successfully deliver dyes or drugs into the cells. The protein-metal hybrid nanocubes can serve as a new type of dual-purpose tool: a blue-emitting cell marker in bioimaging investigation and a nanocarrier in drug delivery studies.