Poly Glycerol Research Articles

Sustained release investigation of curcumin and ciprofloxacin on coaxial electrospun nanocomposite scaffold of poly (3-hydroxybutyrate)-poly glycerol sebacate: an approach for skin regeneration

Sustained release investigation of curcumin and ciprofloxacin on coaxial electrospun nanocomposite scaffold of poly (3-hydroxybutyrate)-poly glycerol sebacate: an approach for skin regeneration

Abstract We012: Sheet like extracellular matrix secreting single cell microvesicles for reprogrammed endothelial cell therapy towards vascular regeneration

To enhance cell survival and engraftment for cell therapy, cell encapsulated injectable biomaterials have been widely used. However, the challenges were hypoxia and nutrient shortage in the core, inflammatory cell infiltration and limited distribution of cells from injection sites. Encapsulation of single cells in sub-100-micron microgels with higher surface to volume ratios provides more efficient oxygen and mass exchange. However, typical production of single-cell-laden microgels by microfluidics devices results in cell damage and compromised biological properties. We hypothesized that stimuli responsive amphiphilic copolymer bearing RGD peptides may self-assemble around single cells induced by cell adhesion moieties would result in single cell microvesicles (MV). A stimuli responsive amphiphilic copolymer GPM (Gelatin Poly glycerol sebacate Methacrylate) was synthesized by grafting hydrophobic synthetic polymer PGS into hydrophilic natural polymer gelatin via methacrylation followed by aza-Michael addition reaction. Single cell microvesicles of endothelial cells (EC-MVs) were fabricated by self-assembly of GPM at room temperature. For in vivo studies, sub-50-micron EC-MVs made of reprogrammed endothelial cells (rECs) were clustered into 200 micron spheres (mGPM) using sodium alginate and injected into a hindlimb ischemia model to investigate cell survival and biological function. The mGPM microspheres functioned as a barrier from immune cell infiltration and also enhanced cellular distribution. The encapsulated rECs were released over 2-4 wks in vivo and were shown robust engraftment, migration, and survival in limb tissues, promoting blood flow recovery and sustained vascular regeneration over 6 months. Interestingly, in in vitro culture, rEC-MVs secreted sheet like extra cellular matrix (ECM) which appeared to make an important role for vessel formation (neovascularization) in vivo (Figure 1). The current study clearly demonstrated the favorable biological applicability of GPM single cell MVs toward vascular regeneration by reprogrammed ECs.

Oral formulations for highly lipophilic drugs: Impact of surface decoration on the efficacy of self-emulsifying drug delivery systems

AimTo evaluate the impact of the surface decoration of cannabidiol (CBD) loaded self-emulsifying drug delivery systems (SEDDS) on the efficacy of the formulations to cross the various barriers faced by orally administered drugs. MethodsPolyethylene glycol (PEG)-free polyglycerol (PG)-based SEDDS, mixed zwitterionic phosphatidyl choline (PC)/PEG-containing SEDDS and PEG-based SEDDS were compared regarding stability against lipid degrading enzymes, surface properties, permeation across porcine mucus, cellular uptake and cytocompatibility. ResultsSEDDS with a size of about 200 nm with narrow size distributions were developed and loaded with 20–21 % of CBD. For PG containing PEG-free SEDDS increased degradation by lipid degrading enzymes was observed compared to PEG-containing formulations. The surface hydrophobicity of placebo SEDDS increased in the order of PG-based to mixed PC/PEG-based to PEG-based SEDDS. The influence of this surface hydrophobicity was also observed on the ability of the SEDDS to cross the mucus gel layer where highest mucus permeation was achieved for most hydrophobic PEG-based SEDDS. Highest cellular internalization was observed for PEG-based Lumogen Yellow (LY) loaded SEDDS with 92 % in Caco-2 cells compared to only 30 % for mixed PC/PEG-based SEDDS and 1 % for PG-based SEDDS, leading to a 100-fold improvement in cellular uptake for SEDDS having highest surface hydrophobicity. For cytocompatibility all developed placebo SEDDS showed similar results with a cell survival of above 75 % for concentrations below 0.05 % on Caco-2 cells. ConclusionHigher surface hydrophobicity of SEDDS to orally deliver lipophilic drugs as CBD seems to be a promising approach to increase the intracellular drug concentration by an enhanced permeation through the mucus layer and cellular internalization.

Optimization and investigation of Physical, chemical, and biological properties of nanofibers produced from (poly glycerol Sebacate-co-caprolactone)/gelatin/peptide and scaffold’s cellular behavior

Recently, peptide and Poly(Glycerol Sebacat) PGS-based materials have garnered significant attention in tissue engineering. In this study, we synthesized two novel nanofibrous webs, namely Poly (glycerol sebacate)/gelatin/peptide (PGS/Gel/PT) and Poly (glycerol sebacate co caprolactone)/gelatin/peptide (P(GScoCL)/Gel/PT), utilizing the electrospinning technique with acetic acid as a cost-effective and eco-friendly solvent. To optimize the diameter of the electrospun nanofibrous samples, we employed response surface methodology and artificial neural network, investigating the impact of various electrospinning parameters. Nanofibrous webs with a diameter of 232 nm under the optimized conditions. Nanofibers were characterized using FTIR, DSC, contact angle measurement, and mechanical testing. The biological properties including biodegradability, cell adhesion, MTT assay, and antibacterial efficacy were performed. Nanofibrous samples antibacterial activity, displaying 99% effectiveness against both Gram-positive and Gramnegative bacteria. Moreover, in-vitro studies on the cellular proliferation of human Mesenchymal Stem Cells (hMSCs) nanofiber scaffold demonstrated normal cell morphology and significantly enhanced cell growth after 4 days.

Enhanced wound regeneration by PGS/PLA fiber dressing containing platelet-rich plasma: an in vitro study

Novel wound dressings with therapeutic effects are being continually designed to improve the wound healing process. In this study, the structural, chemical, physical, and biological properties of an electrospun poly glycerol sebacate/poly lactide acid/platelet-rich plasma (PGS/PLA-PRP) nanofibers were evaluated to determine its impacts on in vitro wound healing. Results revealed desirable cell viability in the Fibroblast (L929) and macrophage (RAW-264.7) cell lines as well as human umbilical vein endothelial cells (HUVEC). Cell migration was evident in the scratch assay (L929 cell line) so that it promoted scratch contraction to accelerate in vitro wound healing. Moreover, addition of PRP to the fiber structure led to enhanced collagen deposition (~ 2 times) in comparison with PGS/PLA scaffolds. While by addition PRP to PGS/PLA fibers not only decreased the expression levels of pro-inflammatory cytokines (IL-6 and TNF-α) in RAW-264.7 cells but also led to significantly increased levels of cytokine (IL-10) and the growth factor (TGF-β), which are related to the anti-inflammatory phase (M2 phenotype). Finally, PGS/PLA-PRP was found to induce a significant level of angiogenesis by forming branching points, loops, and tubes. Based on the results obtained, the PGS/PLA-PRP dressing developed might be a promising evolution in skin tissue engineering ensuring improved wound healing and tissue regeneration.

In Vitro Biocompatibility and Endothelial Permeability of Branched Polyglycidols Generated by Ring-Opening Polymerization of Glycidol with B(C6F5)3 under Dry and Wet Conditions.

Polyglycidol or polyglycerol (PG), a polyether widely used in biomedical applications, has not been extensively studied in its branched cyclic form (bcPG), despite extensive research on hyperbranched PG (HPG). This study explores the biomedical promise of bcPG, particularly its ability to cross the blood-brain barrier (BBB). We evaluate in vitro biocompatibility, endothelial permeability, and formation of branched linear PG (blPG) as topological impurities in the presence of water. Small angle X-ray scattering in solution revealed a fractal dimension of approximately two for bcPG and the mixture bc+blPG, suggesting random branching. Comparisons of cytotoxicity and endothelial permeability between bcPG, bc+blPG, and HPG in a BBB model using hCMEC/D3 cells showed different biocompatibility profiles and higher endothelial permeability for HPG. bcPG showed a tendency to accumulate around cell nuclei, in contrast to the behavior of HPG. This study contributes to the understanding of the influence of polymer topology on biological behavior.

Size, polyglycerol grafting, and net surface charge of iron oxide nanoparticles determine their interaction and toxicity in Caenorhabditis elegans

The widespread application of engineered nanoparticles (NPs) in environmental remediation has raised public concerns about their toxicity to aquatic organisms. Although appropriate surface modification can mitigate the ecotoxicity of NPs, the lack of polymer coating to inhibit toxicity completely and the insufficient knowledge about charge effect hinder the development of safe nanomaterials. Herein, we explored the potential of polyglycerol (PG) functionalization in alleviating the environmental risks of NPs. Iron oxide NPs (ION) of 20, 100, and 200 nm sizes (IONS, IONM and IONL, respectively) were grafted with PG to afford ION-PG. We examined the interaction of ION and ION-PG with Caenorhabditis elegans (C. elegans) and found that PG suppressed non-specific interaction of ION with C. elegans to reduce their accumulation and to inhibit their translocation. Particularly, IONS-PG was completely excluded from worms of all developmental stages. By covalently introducing sulfate, carboxyl and amino groups onto IONS-PG, we further demonstrated that positively charged IONS-PG-NH3+ induced high intestinal accumulation, cuticle adhesion and distal translocation, whereas the negatively charged IONS-PG-OSO3– and IONS-PG-COO– were excreted out. Consequently, no apparent deleterious effects on brood size and life span were observed in worms treated by IONS-PG and IONS-PG bearing negatively charged groups. This study presents new surface functionalization approaches for developing ecofriendly nanomaterials.

In vitro evaluation of physicochemical-dependent effects of polymeric nanoparticles on their cellular uptake and co-localization using pulmonary calu-3 cell lines

Objective The study evaluated physicochemical properties of eight different polymeric nanoparticles (NPs) and their interaction with lung barrier and their suitability for pulmonary drug delivery. Methods Eight physiochemically different NPs were fabricated from Poly lactic-co-glycolic acid (PLGA, PL) and Poly glycerol adipate-co-ω-pentadecalactone (PGA-co-PDL, PG) via emulsification-solvent evaporation. Pulmonary barrier integrity was investigated in vitro using Calu-3 under air-liquid interface. NPs internalization was investigated using a group of pharmacological inhibitors with subsequent microscopic visual confirmation. Results Eight NPs were successfully formulated from two polymers using emulsion-solvent evaporation; 200, 500 and 800 nm, negatively-charged and positively-charged. All different NPs did not alter tight junctions and PG NPs showed similar behavior to PL NPs, indicating its suitability for pulmonary drug delivery. Active endocytosis uptake mechanisms with physicochemical dependent manner were observed. In addition, NPs internalization and co-localization with lysosomes were visually confirmed indicating their vesicular transport. Conclusion PG and PL NPs had shown no or low harmful effects on the barrier integrity, and with effective internalization and vesicular transport, thus, prospectively can be designed for pulmonary delivery applications.

Comparative Analysis of PEG-Free and PEG-Based Self-Emulsifying Drug Delivery Systems for Enhanced Oral Bioavailability of Therapeutic (Poly) Peptides.

This study aims to compare the potential of Polyethylene glycol (PEG-free and PEG-based self-emulsifying drug delivery systems (SEDDS) for the oral administration of insulin glargine (IG). Hydrophobic ion pairs (HIPs) of IG are formed using various counterions. HIPs are assessed for log P octanol/water and dissociation behavior. They are incorporated into SEDDS based on polyglycerol (PG) and zwitterionic surfactant (ZW) using response surface methodology and compared to conventional PEG-SEDDS in size, stability, and log D SEDDS/release medium. Oral IG bioavailability in PG/ZW-SEDDS and PEG-SEDDS is evaluated in rats. Among the various counterions studied, IG-BIS (bis(isotridecyl)sulfosuccinate) HIPs demonstrated the highest log P and an improved dissociation profile. PG/ZW-SEDDS and PEG-SEDDS have similar ≈40nm sizes and are stable over 24 h. Both formulations have log D > 4 in water and >2 in 50mM phosphate buffer pH 6.8. PG/ZW-SEDDS yielded an oral bioavailability of 2.13 ± 0.66% for IG, while the employment of PEG-SEDDS resulted in an oral bioavailability of 1.15 ± 0.35%. This study highlights the prospective utilization of PEG-free SEDDS involving the concurrent application of PG and ZW surfactants, an alternative to conventional PEG surfactants, for improved oral therapeutic (poly) peptide delivery.

An in vitro evaluation of the biocompatibility of proline‐alanine‐serine peptides compared with polyethylene glycol and polyglycerol

AbstractPASylation has been recently reported as a feasible alternative to PEGylation, which in essence is using polypeptides constituted of a combination of proline, alanine and serine for the hydrophilic modification of pharmaceuticals. In this work, we focused on the biocompatibility evaluation of two PAS peptides, (PAS)8 and (PA3)7 as well as the more frequently used polymers polyethylene glycol (PEG) and polyglycerol (PG). It has been verified in this study that (PAS)8 and (PA3)7 both exhibited low cell toxicity against HUVEC and RAW 264.7 cell lines. They also showed negligible RBC hemolysis and agglutination, which demonstrated adequate hemocompatibility. Their potential interactions with bovine serum albumin have also been investigated, and the results indicated little hydrophobic interactions between the polymers and protein. In conclusion, (PAS)8 and (PA3)7 as well as PEG and PG all showed considerable compatibility and safety in these studies, suggesting that (PAS)8 and (PA3)7 could be considered as potential candidates for PEG replacement in future studies.

Polyglycerol-Decorated Hollow Mesoporous Ruthenium Nanoparticles for Long Circulation and Antitumor Effect

Hollow mesoporous ruthenium nanoparticles (HMRu NPs) are especially beneficial for drug delivery and photothermal therapy due to their distinguished specific surface area and photothermal properties. However, poor circulation performance in vivo means that the NPs are subject to rapid clearance before reaching the target tissue. Polyethylene glycol (PEG) modified nanoparticles have become the classical standard to extend circulation by reducing protein adsorption and escaping macrophage phagocytosis, but PEGylation tends to have an accelerated blood clearance effect after repeated use. Considering that the hyperbranched polymers exhibit excellent performance in protein shielding, that makes it possible for them to have the potential to replace PEG. Thus, HMRu NPs were decorated by polyglycerol (PG) in this work compared to PEGylation. The antiprotein adsorption capacity and macrophage escape were assayed by the bicinchoninic acid method and confocal microscopy, suggesting that PG-coating could avoid macrophage phagocytosis more efficiently than PEGylation. Finally, the resultant HMRu-PG could be used as drug carrier for synergistic chemotherapy and photothermal therapy in tumor treatment. This work provides a promising multimodal and versatile nanocarrier in tumor therapy.

Effect of the crosslinking agent on the biorepulsive and mechanical properties of polyglycerol membranes

Polyglycerol (PG) based surfaces materials and surfaces are well-established bio-compatible materials. Crosslinking of the dendrimeric molecules via their OH groups improves their mechanical stability up to the point that free-standing materials can be attained. Here, we investigate the effect of different crosslinkers on PG films regarding their biorepulsivity and mechanical properties. For this purpose, PG films with different thicknesses (15, 50 and 100 nm) were prepared by polymerizing glycidol in a ring-opening polymerization onto hydroxyl-terminated Si substrates. These films were then crosslinked using ethylene glycol diglycidyl ether (EGDGE), divinyl sulfone (DVS), glutaraldehyde (GA), 1,11-di(mesyloxy)−3,6,9-trioxaundecane (TEG-Ms2) or 1,11-dibromo-3,6,9-trioxaundecane (TEG-Br2), respectively. While DVS, TEG-Ms2, and TEG-Br2 resulted in slightly thinned films, presumably due to loss of unbound material, increase of film thickness was observed with GA and, in particular, EDGDE, what can be explained by the different crosslinking mechanisms. The biorepulsive properties of the crosslinked PG films were characterized by water contact angle (WCA) goniometry and various adsorption assays involving proteins (serum albumine, fibrinogen, γ-globulin) and bacteria (E. coli), showing that some crosslinkers (EGDGE, DVS) improved the biorepulsive properties, while others deteriorated them (TEG-Ms2, TEG-Br2, GA). As the crosslinking stabilized the films, it was possible to use a lift-off procedure to obtain free-standing membranes if the thickness of the films was 50 nm or larger. Their mechanical properties were examined with a bulge test showing high elasticities, with the Young’s moduli increasing in the order GA ≈ EDGDE < TEG-Br2 ≈ TEG-Ms2 < DVS.

Polyglycerol‐modified polyvinyl alcohol with improved stability during thermoplastic processing

AbstractPolyvinyl alcohol (PVA), which can be synthesized via a non‐petroleum route, is a multi‐hydroxyl polymer with good comprehensive properties and environmental friendliness. However, poor thermal processability impedes its development. Herein, polyglycerol (PGL) was firstly adopted to substitute parts of glycerin as one of the plasticizers to prepare modified PVA with greater thermal stability. FTIR spectra revealed the strong hydrogen‐bonding interaction between PGL and PVA which would be destroyed during heating, indicating that PGL was suitable for plasticizing PVA. The introduction of PGL weakened the volatilization of plasticizer as T5% of modified PVA was remarkably improved from 174.7°C to 245.8°C with the addition of 20 wt% PGL. The effects of PGL content on the crystallization behaviors, melting characteristics, dynamic rheological behaviors, and mechanical properties of PVA were investigated. It revealed that the substitution of PGL for glycerin did not influence the final crystalline structure and crystallinity of PVA, but shortened the crystallization time, improved the tensile strength and decreased the melt index owing to the entanglement between PVA and PGL molecules. Dynamic oscillatory rheological measurement showed that the lowest complex viscosity was obtained when 10 wt% PGL was incorporated, which is beneficial for practical processing and film forming. Under proper processing conditions, the production and application of this hot‐blown PVA film were realized at an experimental scale. This work sheds light on the exploitation of new plasticizers with high plasticizing efficiency and thermal stability during processing of PVA.

Activation and Inhibition of Isomerization of a Cationic Azobenzene Surfactant in the Large Void Space of Polyglycerol Dendron Micelles.

Owing to the unique geometric structure of dendritic amphiphiles with voluminous dendrons, their micelles can harbor a large void space, which provides a new research focus and approach for micellar functionalization. In this work, we used the void space to construct a UV responsive micelle system of the mixed dendritic amphiphile (C12-(G3)2) and cationic azobenzene surfactant (C4AzoTAB). The synthesized C12-(G3)2 that possesses double third generation polyglycerol (PG) dendrons and a single alkyl chain is expected to highlight the large void space within the inside of the micelles. Thus, the aims of this work are to achieve the isomerization of C4AzoTAB in situ and to deeply understand the intermolecular interaction in the mixed micelles. The effect of the large void room with a wall decorated with the ether oxygen atoms on the isomerization of C4AzoTAB was studied by isomerization kinetics, conductivity measurements, isothermal titration calorimetry (ITC), and 1H NMR and 2D NOESY spectroscopies. The isomerization behavior of C4AzoTAB in C12-(G3)2 micelles was presented in terms of its kinetic constant, counterionic association, interaction enthalpy, and position and orientation of C4AzoTAB. The results of NMR and conductivity show that the quaternary ammonium group of C4AzoTAB situates on the surface of the mixed micelles with C12-(G3)2 both before and after UV-irradiation, while the position of azobenzene group in C12-(G3)2 micelles depends on its conformation. The C12-(G3)2 micelles can inhibit the UV response of the trans-isomer and activate the thermal relaxation of the cis-isomer, which has a potential application in the field of light-controlled smart nanocarriers.

Synthesis of photodynamic intramolecularly crosslinked polyether-copolymers in-chain functionalized with hexaarylbiimidazoles

Intramolecularly crosslinked network polyether-copolymers in-chain functionalized with reversibly photocleavable linkings derived from hexaarylbiimidazoles have been developed, and their nanoparticles were successfully formed in water.

Development of a Potassium-Ion-Responsive Star Copolymer with Controlled Aggregation/Dispersion Transition.

Stimuli-responsive star polymers are promising functional materials whose aggregation, adhesion, and interaction with cells can be altered by applying suitable stimuli. Among several stimuli assessed, the potassium ion (K+), which is known to be captured by crown ethers, is of considerable interest because of the role it plays in the body. In this study, a K+-responsive star copolymer was developed using a polyglycerol (PG) core and grafted copolymer arms consisting of a thermo-responsive poly(N-isopropylacrylamide) unit, a metal ion-recognizing benzo-18-crown-6-acrylamide unit, and a photoluminescent fluorescein O-methacrylate unit. Via optimization of grafting density and copolymerization ratio of grafted arms, along with the use of hydrophilic hyperbranched core, microsized aggregates with a diameter of 5.5 μm were successfully formed in the absence of K+ ions without inducing severe sedimentation (the lower critical solution temperature (LCST) was 35.6 °C). In the presence of K+ ions, these aggregates dispersed due to the shift in LCST (47.2 °C at 160 mM K+), which further induced the activation of fluorescence that was quenched in the aggregated state. Furthermore, macrophage targeting based on the micron-sized aggregation state and subsequent fluorescence activation of the developed star copolymers in response to an increase in intracellular K+ concentration were performed as a potential K+ probe or K+-responsive drug delivery vehicle.

Emulsification – A promising approach to improve performance and reduce exhaust emissions of a biodiesel fuelled light-duty diesel engine

The effectiveness of employing emulsions prepared with water and ethanol to reduce the inherently higher levels of oxides of nitrogen (NOx) emission with biodiesel, whilst improving or maintaining the smoke emission, is investigated in the present work. To facilitate a one-to-one comparison, the water/ethanol to biodiesel ratio for the emulsions was similar at 18% by mass. Experiments were conducted on a light-duty diesel engine at a constant speed and varying loads with diesel, biodiesel, biodiesel-water and biodiesel-ethanol emulsions. A novel surfactant, Poly Glycerol Poly Ricinoleate (PGPR), was used for preparing biodiesel-water emulsion that exhibited no phase separation for over four months. The results obtained with both emulsions were compared with neat biodiesel as the reference fuel. Ignition delay and peak pressure increased for both emulsions. The biodiesel-water emulsion resulted in advanced combustion phasing while it was retarded with ethanol emulsion. The brake thermal efficiency increased with biodiesel-water emulsion up to 7% at 6.3 bar brake mean effective pressure (BMEP) while at 3% with ethanol emulsion. The brake specific fuel consumption (BSFC) was reduced by 20% with biodiesel-water emulsion, while it remained the same as biodiesel with ethanol emulsion. The emulsions simultaneously reduced NOx and smoke emissions; the biodiesel-water emulsion was more effective, resulting in a maximum reduction of 45% and 37% in NOx and smoke emissions, respectively. The biodiesel-water emulsion also significantly reduced carbon monoxide (CO) emissions, with a maximum reduction of 54% at 6.3 bar BMEP. Overall, the emulsification of biodiesel provides considerable benefits in terms of reduced exhaust emissions and improved engine performance.

High-Purity Corundum as Support for Affinity Extractions from Complex Samples

Nonporous corundum powder, known as an abrasive material in the industry, was functionalized covalently with protein binders to isolate and enrich specific proteins from complex matrices. The materials based on corundum were characterized by TEM, ESEM, BET, DLS, EDS, and zeta potential measurements. The strong Al-O-P bonds between the corundum surface and amino phosphonic acids were used to introduce functional groups for further conjugations. The common crosslinker glutaraldehyde was compared with a hyperbranched polyglycerol (PG) of around 10 kDa. The latter was oxidized with periodate to generate aldehyde groups that can covalently react with the amines of the surface and the amino groups from the protein via a reductive amination process. The amount of bound protein was quantified via aromatic amino acid analysis (AAAA). This work shows that oxidized polyglycerol can be used as an alternative to glutaraldehyde. With polyglycerol, more of the model protein bovine serum albumin (BSA) could be attached to the surface under the same conditions, and lower non-specific binding (NSB) was observed. As a proof of concept, IgG was extracted with protein A from crude human plasma. The purity of the product was examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). A binding capacity of 1.8 mg IgG per gram of corundum powder was achieved. The advantages of corundum include the very low price, extremely high physical and chemical stability, pressure resistance, favorable binding kinetics, convenient handling, and flexible application.

Water-soluble ZnO quantum dots modified by polyglycerol: The pH-sensitive and targeted fluorescent probe for delivery of an anticancer drug

Efficacious specific anticancer drug delivery on the tumor site is the basic title of many investigations. In this paper we reported photoluminescence ZnO quantum dots (ZnO QDs) as a pH-responsive platform for delivery of anticancer drug doxorubicin (DOX). Biocompatible ZnO QDs was synthesized using zinc acetate in the alkaline medium. To improve the nanoparticles aqueous dispersion, ZnO QDs are directly functionalized with polyglycerol (PG) through ring-opening polymerization of glycidol. Moreover, folic acid was conjugated to the end of polyglycerol chains through esterification reaction to target the nanoparticles for cancer cells (ZnO QD-PG-FA). These nanocarriers were characterized by different techniques. The HRTEM images confirmed a final size of about 10 nm for ZnO QD-PG-FA. Doxorubicin was loaded on the ZnO QD-PG-FA in a different carrier: drug weight ratios. The photoluminescence property of ZnO QDs was remained after surface modification with PG, FA, and drug loading. The results showed that the drug was immediately released in acidic intracellular environments of tumor cells, while at neutral pH the complex was stable. Cell cytotoxicity assay confirmed the antitumor activity of DOX-ZnO QDs-PG-FA. Therefore, ZnO QD-PG-FA provides a valuable platform that can use as a diagnostic, targeting, and pH-responsive delivery of anticancer drug for tumor therapy.

Polyglycerol Functionalized 10 B Enriched Boron Carbide Nanoparticle as an Effective Bimodal Anticancer Nanosensitizer for Boron Neutron Capture and Photothermal Therapies.

Boron neutron capture therapy (BNCT) is a non-invasive cancer treatment with little adverse effect utilizing nuclear fission of 10 B upon neutron irradiation. While neutron source has been developed from a nuclear reactor to a compact accelerator, only two kinds of drugs, boronophenylalanine and sodium borocaptate, have been clinically used for decades despite their low tumor specificity and/or retentivity. To overcome these challenges, various boron-containing nanomaterials, or "nanosensitizers", have been designed based on micelles, (bio)polymers and inorganic nanoparticles. Among them, inorganic nanoparticles such as boron carbide can include a much higher 10 B content, but successful in vivo applications are very limited. Additionally, recent reports on the photothermal effect of boron carbide are motivating for the addition of another modality of photothermal therapy. In this study, 10 B enriched boron carbide (10 B4 C) nanoparticle is functionalized with polyglycerol (PG), giving 10 B4 C-PG with enough dispersibility in a physiological environment. Pharmacokinetic experiments show that 10 B4 C-PG fulfills the following three requirements for BNCT; 1) low intrinsic toxicity, 2) 10 B in tumor/tumor tissue (wt/wt) ≥ 20ppm, and 3) 10 B concentrations in tumor/blood ≥ 3. In vivo study reveals that neutron irradiation after intravenous administration of 10 B4 C-PG suppresses cancer growth significantly and eradicates cancer with the help of near-infrared light irradiation.