Enhancing the therapeutic potential of isoliensinine for hypertension through PEG-PLGA nanoparticle delivery: A comprehensive in vivo and in vitro study.

BACKGROUND: Hypertension, a highly prevalent chronic disease, is known to inflict severe damage upon blood vessels. In our previous study, isoliensinine, a kind of bibenzyl isoquinoline alkaloid which isolated from a TCM named Lotus Plumule (Nelumbo nucifera Gaertn), exhibits antihypertensive and vascular smooth muscle proliferation-inhibiting effects, but its application is limited due to poor water solubility and low bioavailability. In this study, we proposed to prepare isoliensinine loaded by PEG-PLGA polymer nanoparticles to increase its efficacy METHOD: We synthesized and thoroughly characterized PEG-PLGA nanoparticles loaded with isoliensinine using a nanoprecipitation method, denoted as, PEG-PLGA@Isoliensinine. Additionally, we conducted comprehensive investigations into the stability of PEG-PLGA@Isoliensinine, in vitro drug release profiles, and in vivo pharmacokinetics. Furthermore, we assessed the antihypertensive efficacy of this nano-system through in vitro experiments on A7R5 cells and in vivo studies using AngII-induced mice. RESULT: The findings reveal that PEG-PLGA@Isoliensinine significantly improves isoliensinine absorption by A7R5 cells and enhances targeted in vivo distribution. This translates to a more effective reduction of AngII-induced hypertension and vascular smooth muscle proliferation. CONCLUSION: In this study, we successfully prepared PEG-PLGA@Isoliensinine by nano-precipitation, and we confirmed that PEG-PLGA@Isoliensinine surpasses free isoliensinine in its effectiveness for the treatment of hypertension, as demonstrated through both in vivo and in vitro experiments. SIGNIFICANCE: This study lays the foundation for isoliensinine's clinical use in hypertension treatment and vascular lesion protection, offering new insights for enhancing the bioavailability of traditional Chinese medicine components. Importantly, no toxicity was observed, affirming the successful implementation of this innovative drug delivery system in vivo and offers a promising strategy for enhancing the effectiveness of Isoliensinine and propose an innovative avenue for developing novel formulations of traditional Chinese medicine monomers.

PEGylated chitosan-coated nanophotosensitizers for effective cancer treatment by photothermal-photodynamic therapy combined with glutathione depletion.

The combination of photothermal therapy (PTT) and photodynamic therapy (PDT) has emerged as a promising strategy for cancer treatment. However, the poor photostability and photothermal conversion efficiency (PCE) of organic small-molecule photosensitizers, and the intracellular glutathione (GSH)-mediated singlet oxygen scavenging largely decline the antitumor efficacy of PTT and PDT. Herein, a versatile nanophotosensitizer (NPS) system is developed by ingenious incorporation of indocyanine green (ICG) into the PEGylated chitosan (PEG-CS)-coated polydopamine (PDA) nanoparticles via multiple π-π stacking, hydrophobic and electrostatic interactions. The PEG-CS-covered NPS showed prominent colloidal and photothermal stability as well as high PCE (ca 62.8 %). Meanwhile, the Michael addition between NPS and GSH can consume GSH, thus reducing the GSH-induced singlet oxygen scavenging. After being internalized by CT26 cells, the NPS under near-infrared laser irradiation produced massive singlet oxygen with the aid of thermo-enhanced intracellular GSH depletion to elicit mitochondrial damage and lipid peroxide formation, thus leading to ferroptosis and apoptosis. Importantly, the combined PTT and PDT delivered by NPS effectively inhibited CT26 tumor growth in vivo by light-activated intense hyperthermia and redox homeostasis disturbance. Overall, this work presents a new tactic of boosting antitumor potency of ICG-mediated phototherapy by PEG-CS-covered NPS.

Development of lactic acid based chain extender and soybean oil-derived polyurethanes for ecofriendly sustained drug delivery systems.

In the present study, a range of sustainable, biocompatible and biodegradable polyurethanes (PU-1 to PU-4) were synthesized using different combinations of biobased polyol (obtained through the epoxidation of soybean oil, followed by ring opening with ethanol) and polyethylene glycol (PEG) and isophorone diisocyanate. The sustainable chain extender used in this study was synthesized by the esterification of lactic acid with ethylene glycol (EG). The synthesized PU samples were characterized through scanning electron microscopy (SEM), Fourier transformed infrared (FTIR) and nuclear magnetic resonance (1H NMR and 13C NMR) spectroscopy. Wetting ability and thermal degradation analysis (TGA) of the samples were also studied. Subsequently, these PUs were examined as potential drug delivery systems using Gabapentin as a model drug, which was loaded in the polymer matrix using the solvent evaporation method. The drug release studies were carried out in 0.06 N HCl as a release medium according to the method outlined in the United States Pharmacopeia. The maximum drug release was observed for sample PU-P1, which was found to be 53.0 % after 6 h. Moreover, a comparison of different PU samples revealed a trend wherein the values of drug release were decreased with an increase in the PEG content.

Synthesis and biodegradation testing of some synthetic oils based on ester.

Synthetic ester oils are widely used in many applications due to their ideal cleaning properties, lubricating performance and assured polarity. The majority of esters oils are more biodegradable. than any other base stock. For instance, oil soluble polyalkyleneglycols (PAGs) or polyalphaolephins (PAOs), are only biodegradable in the lower viscosity grades. The goal of this study is to create some synthetic base oils by two major protocols; the first is esterifying valeric acid with various glycols (ethylene glycol, propylene glycol, butylene glycol and poly (ethylene glycol 400). The second involves esterification of propanoic acid, heptanoic acid, or octanoic acid with ethylene glycol. The reaction yield varies between 85 and 94%. The chemical composition of the prepared esters was examined using various spectroscopic methods (Fourier-transform infrared (FT-IR) and proton nuclear magnetic resonance (1H-NMR) spectroscopy. The thermal properties investigation by thermo gravimetric analysis (TGA) showed pronounced thermal stability of the prepared esters. The biodegradability was verified versus two bacterial isolates (B1, B2). The results showed that percentage of degradation of the lube oil was in the range of 34% to 84% after 3 days of incubation. Moreover, the rheological study revealed that the prepared esters exhibited Newtonian rheological behaviours. Viscosity examination displayed that the esters based on ethylene glycol, such as (A), had the highest VI: 179 values when compared to those based on higher glycols. Viscosity and viscosity index results showed slight increase as the number of carbon atoms in the acid chain increases. At last, most of the synthesized esters possessed pour points ≤ - 32 °C: ≤ - 40 except in case of using higher acids like heptanoic acid and octanoic acid in preparation the pour point increases to - 9 °C and - 15 °C.

Tumor-activated targetable photothermal chemotherapy using IR780/zoledronic acid-containing hybrid polymeric nanoassemblies with folate modification to treat aggressive breast cancer.

To effectively treat aggressive breast cancer by tumor-activated targetable photothermal chemotherapy, in this work, folate (FA)-modified hybrid polymeric nanoassemblies (HPNs) with a poly(ethylene glycol) (PEG)-detachable capability are developed as vehicles for tumor-targeted co-delivery of IR780, a lipophilic photothermal reagent, and zoledronic acid (ZA), a hydrophilic chemotherapy drug. Through hydrophobic interaction-induced co-assembly, IR780 molecules and ZA/poly(ethylenimine) (PEI) complexes were co-encapsulated into a poly(lactic-co-glycolic acid) (PLGA)-rich core stabilized by the amphiphilic FA-modified D-α-tocopheryl poly(ethylene glycol) succinate (FA-TPGS) and acidity-sensitive PEG-benzoic imine-octadecane (C18) (PEG-b-C18) conjugates. The developed FA-ZA/IR780@HPNs with high ZA and IR780 payloads not only showed excellent colloidal stability in a serum-containing milieu, but also promoted IR780-based photostability and photothermal conversion efficiency. Furthermore, for FA-ZA/IR780@HPNs under simulated physiological conditions, the premature leakage of IR780 and ZA molecules was remarkably declined. In a mimetic acidic tumor microenvironment, the uptake of FA-ZA/IR780@HPNs by FA receptor-overexpressed 4T1 breast cancer cells was remarkably promoted by PEG detachment combined with FA receptor-mediated endocytosis, thus effectively hindering migration of cancer cells and augmenting the anticancer efficacy of photothermal chemotherapy. Notably, the in vivo studies demonstrated that the FA-ZA/IR780@HPNs largely deposited at 4T1 tumor sites and profoundly suppressed tumor growth and metastasis without severe systemic toxicity upon near infrared (NIR)-triggered IR780-mediated hyperthermia integrated with ZA chemotherapy. This work presents a practical strategy to treat aggressive breast tumors with tumor-triggered targetable photothermal chemotherapy using FA-ZA/IR780@HPNs.

Novel indocyanine green-loaded photothermal nanoparticles targeting TRPV1 for thermal ablation treatment of severe murine asthma induced by ovalbumin and lipopolysaccharide.

To identify a replacement strategy for bronchial thermoplasty (BT) with non-invasive and free-of-severe side effect is urgently needed in the clinic for severe asthma treatment. In this study, PLGA-PEG@ICG@TRPV1 pAb (PIT) photothermal nanoparticles targeting bronchial TRPV1 were designed for photothermal therapy (PTT) against severe murine asthma induced by ovalbumin and lipopolysaccharide. PIT was formulated with a polyethylene glycol (PEG)-grafted poly (lactic-co-glycolic) acid (PLGA) coating as a skeleton structure to encapsulate indocyanine green (ICG) and was conjugated to the polyclonal antibody against transient receptor potential vanilloid 1 (TRPV1 pAb). The results revealed that PIT held good druggability due to its electronegativity and small diameter. PIT demonstrated great photothermal effects both in vivo and in vitro and exhibited good ability to target TRPV1 in vitro because of its selective cell uptake and specific cell toxicity toward TRPV1-overexpressing cells. The PIT treatment effectively reduced asthma symptoms in mice. This is evident from improvements in expiratory airflow limitation, significant decreases in inflammatory cell infiltration in the airways, and increases in goblet cell and columnar epithelial cell proliferation. In conclusion, PIT alleviates severe murine asthma symptoms through a combination of TRPV1 targeting and photothermal effects.

Polydopamine-Modified 2D Iron (II) Immobilized MnPS3 Nanosheets for Multimodal Imaging-Guided Cancer Synergistic Photothermal-Chemodynamic Therapy.

Manganese phosphosulphide (MnPS3 ), a newly emerged and promising member of the 2D metal phosphorus trichalcogenides (MPX3 ) family, has aroused abundant interest due to its unique physicochemical properties and applications in energy storage and conversion. However, its potential in the field of biomedicine, particularly as a nanotherapeutic platform for cancer therapy, has remained largely unexplored. Herein, a 2D "all-in-one" theranostic nanoplatform based on MnPS3 is designed and applied for imaging-guided synergistic photothermal-chemodynamic therapy. (Iron) Fe (II) ions are immobilized on the surface of MnPS3 nanosheets to facilitate effective chemodynamic therapy (CDT). Upon surface modification with polydopamine (PDA) and polyethylene glycol (PEG), the obtained Fe-MnPS3 /PDA-PEG nanosheets exhibit exceptional photothermal conversion efficiency (η = 40.7%) and proficient pH/NIR-responsive Fenton catalytic activity, enabling efficient photothermal therapy (PTT) and CDT. Importantly, such nanoplatform can also serve as an efficient theranostic agent for multimodal imaging, facilitating real-time monitoring and guidance of the therapeutic process. After fulfilling the therapeutic functions, the Fe-MnPS3 /PDA-PEG nanosheets can be efficiently excreted from the body, alleviating the concerns of long-term retention and potential toxicity. This work presents an effective, precise, and safe 2D "all-in-one" theranostic nanoplatform based on MnPS3 for high-efficiency tumor-specific theranostics.

Vitexin-loaded poly(ethylene glycol) methyl ether-grafted chitosan/alginate nanoparticles: preparation, physicochemical properties and in vitro release behaviors.

BACKGROUND: Vitexin, a flavonoid in various foods and medicinal plants, has potential clinical, therapeutic and food applications due to its bioactive properties and beneficial health effects. However, its poor water solubility causes low oral bioavailability and poor absorption in the gastrointestinal tract, limiting its practical applications. Encapsulation is an efficient approach to overcome these limitations. This study demonstrates the encapsulation of vitexin into poly(ethylene glycol) methyl ether-grafted chitosan (mPEG-g-CTS)/alginate (ALG) polyelectrolyte complex nanoparticles. RESULTS: The vitexin-loaded mPEG-g-CTS/ALG nanoparticles were characterized by Fourier transform infrared spectroscopy, ultraviolet-visible spectroscopy and X-ray diffraction. The vitexin-loaded mPEG-g-CTS/ALG nanoparticles had a spherical shape, 50-200 nm in diameter, and negatively charged surface (-27 to -38 mV). They possessed a loading capacity of 4-60%, encapsulation efficiency of 50-100% and antioxidant activity (30-52% 2,2-diphenyl-1-picrylhydrazyl decoloration) when their initial vitexin content was 0.02-0.64 g g-1 polymers. Successful vitexin loading into mPEG-g-CTS/ALG nanoparticles was also indirectly confirmed by the enhanced thermal stability of both polymers and the residual soybean oil used in the emulsion preparation step and delayed oxidative degradation of the residual soybean oil. Vitexin's in vitro release from the mPEG-g-CTS/ALG nanoparticles was very fast in phosphate buffer at pH 11, followed by pH 7, and very slow in acetate buffer at pH 3. The gastrointestinal digestion of vitexin increased by encapsulating into mPEG-g-CTS/ALG nanoparticles. CONCLUSIONS: Vitexin-loaded mPEG-g-CTS/ALG nanoparticles were successfully fabricated using a two-step process of oil-in-water emulsion and ionic gelation without the use of pungent odor acids and other crosslinkers. The obtained nanoparticles are suitable for oral intestinal-specific delivery systems. © 2023 Society of Chemical Industry.

[Establishment of a quantitative method for GC analysis of polyoxyethylene (35) castor oil in microemulsion extracts].

With the continuous exploration of microemulsions as solvents for traditional Chinese medicine extraction, polyoxyethy-lene(35) castor oil(CrEL), a commonly used surfactant, is being utilized by researchers. However, the problem of detecting residues of this surfactant in microemulsion extracts has greatly hampered the further development of microemulsion solvents. Based on the chemical structures of the components in CrEL and the content determination method of castor oil in the 2020 edition of the Chinese Pharmacopoeia(Vol. Ⅳ), this study employed gas chromatography(GC) and single-factor experiments to optimize the preparation method of methyl ricinoleate from CrEL. The conversion coefficient between the two was validated, and the optimal sample preparation method was used to process microemulsion extracts of Zexie Decoction from three batches. The content of methyl ricinoleate generated was determined, and the content of CrEL in the microemulsion extracts of Zexie Decoction was calculated using the above conversion coefficient. The results showed that the optimal preparation method for CrEL was determined. Specifically, 10 mL of 1 mol·L~(-1) KOH-methanol solution was heated at 60 ℃ for 15 min in a water bath. Subsequently, 10 mL of boron trifluoride etherate-methanol(1∶3) solution was heated at 60 ℃ for 15 min in a water bath, followed by extraction with n-hexane twice. CrEL could stably produce 20.84% methyl ricinoleate. According to this conversion coefficient, the average mass concentration of CrEL in the three batches of Zexie Decoction microemulsion extracts was 11.94 mg·mL~(-1), which was not significantly different from the CrEL mass concentration of 11.57 mg·mL~(-1) during microemulsion formulation, indicating that the established content determination method of this study was highly accurate, sensitive, and repeatable. It can be used for subsequent research on microemulsion extracts of Zexie Decoction and provide a reference for quality control of other drug formulations containing CrEL.

An autocatalytic multicomponent DNAzyme nanomachine for tumor-specific photothermal therapy sensitization in pancreatic cancer.

Multicomponent deoxyribozymes (MNAzymes) have great potential in gene therapy, but their ability to recognize disease tissue and further achieve synergistic gene regulation has rarely been studied. Herein, Arginylglycylaspartic acid (RGD)-modified Distearyl acylphosphatidyl ethanolamine (DSPE)-polyethylene glycol (PEG) (DSPE-PEG-RGD) micelle is prepared with a DSPE hydrophobic core to load the photothermal therapy (PTT) dye IR780 and the calcium efflux pump inhibitor curcumin. Then, the MNAzyme is distributed into the hydrophilic PEG layer and sealed with calcium phosphate through biomineralization. Moreover, RGD is attached to the outer tail of PEG for tumor targeting. The constructed nanomachine can release MNAzyme and the cofactor Ca2+ under acidic conditions and self-assemble into an active mode to cleave heat shock protein (HSP) mRNA by consuming the oncogene miRNA-21. Silencing miRNA-21 enhances the expression of the tumor suppressor gene PTEN, leading to PTT sensitization. Meanwhile, curcumin maintains high intracellular Ca2+ to further suppress HSP-chaperone ATP by disrupting mitochondrial Ca2+ homeostasis. Therefore, pancreatic cancer is triple-sensitized to IR780-mediated PTT. The in vitro and in vivo results show that the MNAzyme-based nanomachine can strongly regulate HSP and PTEN expression and lead to significant pancreatic tumor inhibition under laser irradiation.

NIR-II responsive PEGylated MoO2 nanocrystals with LSPR for efficient photothermal and photodynamic performance enhancement.

Phototherapy, including photothermal and photodynamic therapy, has gained extensive attention in the tumor treatment field recently, while synergistic therapy can significantly improve curative effects. However, a complicated photo-responsive nanosystem, different excitation wavelengths, and low tissue depth hindered its actual application. Herein, single near-infrared responsive PEGylated defective MoO2 nanocrystals were fabricated by a green hydrothermal method. The photothermal and photodynamic performances of the samples were presented in detail under a safe power of 1064 nm (NIR-II, 1.0 W cm-2). Interestingly, the photodynamic properties were prompted by the localized surface plasmon resonance (LSPR) photothermal effect obviously, and the collaborative enhancement mechanism was explored in depth. Subsequently, the in vitro cytotoxicity was evaluated on the 4T1 cancer cells under NIR-II irradiation. This work may provide guidance for the facile fabrication of TMOs for NIR-II responsive and enhanced dual-modal phototherapy.

Mechanistic Study on the Degradation of Hydrolysable Core-Crosslinked Polymeric Micelles.

Core-crosslinked polymeric micelles (CCPMs) are an attractive class of nanocarriers for drug delivery. Two crosslinking approaches to form CCPMs exist: either via a low-molecular-weight crosslinking agent to connect homogeneous polymer chains with reactive handles or via cross-reactive handles on polymers to link them to each other (complementary polymers). Previously, CCPMs based on methoxy poly(ethylene glycol)-b-poly[N-(2-hydroxypropyl) methacrylamide-lactate] (mPEG-b-PHPMAmLacn) modified with thioesters were crosslinked via native chemical ligation (NCL, a reaction between a cysteine residue and thioester resulting in an amide bond) using a bifunctional cysteine containing crosslinker. These CCPMs are degradable under physiological conditions due to hydrolysis of the ester groups present in the crosslinks. The rapid onset of degradation observed previously, as measured by the light scattering intensity, questions the effectiveness of crosslinking via a bifunctional agent. Particularly due to the possibility of intrachain crosslinks that can occur using such a small crosslinker, we investigated the degradation mechanism of CCPMs generated via both approaches using various analytical techniques. CCPMs based on complementary polymers degraded slower at pH 7.4 and 37 °C than CCPMs with a crosslinker (the half-life of the light scattering intensity was approximately 170 h versus 80 h, respectively). Through comparative analysis of the degradation profiles of the two different CCPMs, we conclude that partially ineffective intrachain crosslinks are likely formed using the small crosslinker, which contributed to more rapid CCPM degradation. Overall, this study shows that the type of crosslinking approach can significantly affect degradation kinetics, and this should be taken into consideration when developing new degradable CCPM platforms.

Development of κ-carrageenan-PEG/lecithin bioactive hydrogel membranes for antibacterial adhesion and painless detachment.

The issue of wound dressing adherence poses a substantial challenge in the field of wound care, with implications both clinically and economically. Overcoming this challenge requires the development of a hydrogel dressing that enables painless removal without causing any secondary damage. However, addressing this issue still remains a significant challenge that requires attention and further exploration. The present study is focused on the synthesis of hydrogel membranes based on κ-carrageenan (CG), polyethylene glycol (PEG), and soy lecithin (LC), which can provide superior antioxidant and antibacterial attachment properties with a tissue anti adhesion activity for allowing an easy removability without causing secondary damage. The (CG-PEG)/LC mass ratio was varied to fabricate hydrogel membranes via a facile approach of physical blending and solution casting. The physicochemical properties of (CG-PEG)/LC hydrogel membranes were studied by scanning electron microscopy (SEM), Fourier transforms infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and mechanical analyses. The membranes showed significantly enhanced mechanical properties with excellent flexibility and had high swelling capacity (˃1000 %), which would provide a moist condition for wound healing. The membranes also exhibited excellent free radical scavenging ability (>60 %). In addition, the (CG-PEG)/LC hydrogel membranes showed reduced peel strength 26.5 N/m as a result of weakening the hydrogel-gelatin interface during an in vitro gelatin peeling test. Moreover, the membrane showed superior antibacterial adhesion activity (>90 %) against both S. aureus and E. coli due to the presence of both PEG and LC. The results also suggested that the hydrogel membranes exhibit NIH3T3 cell antiadhesion property, making them promising material for easy detachment from the healed tissue without causing secondary damage. Thus, this novel combination of (CG-PEG)/LC hydrogel membranes have immense application potential as a biomaterial in the healthcare sector.

Preparation, characterization, and evaluation of the antitumor effect of kaempferol nanosuspensions.

Kaempferol (KAE) is a naturally occurring flavonoid compound with antitumor activity. However, the low aqueous solubility, poor chemical stability, and suboptimal bioavailability greatly restrict its clinical application in cancer therapy. To address the aforementioned limitations and augment the antitumor efficacy of KAE, we developed a kaempferol nanosuspensions (KAE-NSps) utilizing D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) as a stabilizing agent, screened the optimal preparation process, and conducted a comprehensive investigation of their fundamental properties as well as the antitumor effects in the study. The findings indicated that the particle size was 186.6 ± 2.6 nm of the TPGS-KAE-NSps optimized, the shape of which was fusiform under the transmission electron microscope. The 2% (w/v) glucose was used as the cryoprotectant for TPGS-KAE-NSps, whose drug loading content was 70.31 ± 2.11%, and the solubility was prominently improved compared to KAE. The stability and biocompatibility of TPGS-KAE-NSps were favorable and had a certain sustained release effect. Moreover, TPGS-KAE-NSps clearly seen to be taken in the cytoplasm exhibited a stronger cytotoxicity and suppression of cell migration, along with increased intracellular ROS production and higher apoptosis rates compared to KAE in vitro cell experiments. In addition, TPGS-KAE-NSps had a longer duration of action in mice, significantly improved bioavailability, and showed a stronger inhibition of tumor growth (the tumor inhibition rate of high dose intravenous injection group was 68.9 ± 1.46%) than KAE with no obvious toxicity in 4T1 tumor-bearing mice. Overall, TPGS-KAE-NSps prepared notably improved the defect and the antitumor effects of KAE, making it a promising nanodrug delivery system for KAE with potential applications as a clinical antitumor drug.

Influence of the modifiers in polyol method on magnetically induced hyperthermia and biocompatibility of ultrafine magnetite nanoparticles.

Magnetite nanoparticles (Fe3O4 NPs) are widely tested in various biomedical applications, including magnetically induced hyperthermia. In this study, the influence of the modifiers, i.e., urotropine, polyethylene glycol, and NH4HCO3, on the size, morphology, magnetically induced hyperthermia effect, and biocompatibility were tested for Fe3O4 NPs synthesized by polyol method. The nanoparticles were characterized by a spherical shape and similar size of around 10 nm. At the same time, their surface is functionalized by triethylene glycol or polyethylene glycol, depending on the modifiers. The Fe3O4 NPs synthesized in the presence of urotropine had the highest colloidal stability related to the high positive value of zeta potential (26.03 ± 0.55 mV) but were characterized by the lowest specific absorption rate (SAR) and intrinsic loss power (ILP). The highest potential in the hyperthermia applications have NPs synthesized using NH4HCO3, for which SAR and ILP were equal to 69.6 ± 5.2 W/g and 0.613 ± 0.051 nHm2/kg, respectively. Their application possibility was confirmed for a wide range of magnetic fields and by cytotoxicity tests. The absence of differences in toxicity to dermal fibroblasts between all studied NPs was confirmed. Additionally, no significant changes in the ultrastructure of fibroblast cells were observed apart from the gradual increase in the number of autophagous structures.

Donor-acceptor-donor small molecules for fluorescence/photoacoustic imaging and integrated photothermal therapy.

Here, a D-A-D type fluorescent conjugated molecule with a high molar absorption coefficient and emission at 1120 nm in the near-infrared region was synthesized. Conjugated molecules and two polyethylene glycol polymers with different lipophilic ends are assembled into water-soluble nanoparticles to improve their biocompatibility. Then, their physical and chemical properties were studied and compared. Compared with phospholipid-based PEG, styrene-based PEG can reduce the π-π stacking between molecules and the quenching caused by molecular aggregation. It has more advantages in particle size and fluorescence performance and can be better used in biological imaging. In addition, the Nano-particles have good photo-thermal conversion efficiency; the temperature rises to 62.8°C after 980 nm irradiation for 6 min, which can be used as a potential near-infrared II photothermal therapeutic agent. In vivo imaging experiments confirmed that nanomaterials have fluorescence, photoacoustic dual-modal imaging and good biological safety. STATEMENT OF SIGNIFICANCE: In this work, we constructed D-A-D type dual donor fluorescent molecules using BBTD, CPDT and EDOT, and used amphiphilic polymers to improve their biocompatibility. Compared with DSPE NPs, PS-NPs can reduce intermolecular π-π stacking and increase quantum yield (QY = 0.98 %). Deep penetration and low biological toxicity make it have biomedical value and realize the integration of multi-functional collaborative imaging. This work can still be further improved and supplemented, and the molecular structure can be optimized to improve its application in biomedical imaging.

Dual role of polyglycerol vitamin E succinate in emulsions: An efficient antioxidant emulsifier.

α-Tocopherol, as an oil-soluble vitamin with strong antioxidant activity. It is the most naturally abundant and biologically active form of vitamin E in humans. In this study, a novel emulsifier (PG20-VES) was synthesized by attaching hydrophilic twenty-polyglycerol (PG20) to hydrophobic vitamin E succinate (VES). This emulsifier was shown to have a relatively low critical micelle concentration (CMC = 3.2 µg/mL). The antioxidant activities and emulsification properties of PG20-VES were compared with those of a widely used commercial emulsifier: D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS). PG20-VES exhibited a lower interfacial tension, stronger emulsifying capacity and similar antioxidant property to TPGS. An in vitro digestion study showed that lipid droplets coated by PG20-VES were digested under simulated small intestine conditions. This study showed that PG20-VES is an efficient antioxidant emulsifier, which may have applications in the formulation of bioactive delivery systems in the food, supplement, and pharmaceutical industries.

Targeted delivery of paclitaxel drug using polymer-coated magnetic nanoparticles for fibrosarcoma therapy: in vitro and in vivo studies.

Fibrosarcoma is a rare type of cancer that affects cells known as fibroblasts that are malignant, locally recurring, and spreading tumor in fibrous tissue. In this work, an iron plate immersed in an aqueous solution of double added deionized water, supplemented with potassium permanganate solution (KMnO4) was carried out by the pulsed laser ablation in liquid method (PLAIL). Superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized using different laser wavelengths (1064, 532, and 266 nm) at a fluence of 28 J/cm2 with 100 shots of the iron plate to control the concentration, shape and size of the prepared high-stability SPIONs. The drug nanocarrier was synthesized by coating SPION with paclitaxel (PTX)-loaded chitosan (Cs) and polyethylene glycol (PEG). This nanosystem was functionalized by receptors that target folate (FA). The physiochemical characteristics of SPION@Cs-PTX-PEG-FA nanoparticles were evaluated and confirmed by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-Ray diffraction (XRD), atomic force microscopy (AFM), and dynamic light scattering (DLS) methods. Cell internalization, cytotoxicity assay (MTT), apoptosis induction, and gene expression of SPION@Cs-PTX-PEG-FA were estimated in fibrosarcoma cell lines, respectively. In vivo studies used BALB/c tumor-bearing mice. The results showed that SPION@Cs-PTX-PEG-FA exhibited suitable physical stability, spherical shape, desirable size, and charge. SPION@Cs-PTX-PEG-FA inhibited proliferation and induced apoptosis of cancer cells (P < 0.01). The results of the in vivo study showed that SPION@Cs-PTX-PEG-FA significantly decreased tumor size compared to free PTX and control samples (P < 0.05), leading to longer survival, significantly increased splenocyte proliferation and IFN-γ level, and significantly decreased the level of IL-4. All of these findings indicated the potential of SPION@Cs-PTX-PEG-FA as an antitumor therapeutic agent.

Synthesis and Characterizations of Bioactive Glass Nanoparticle-Incorporated Triblock Copolymeric Injectable Hydrogel for Bone Tissue Engineering.

Recently, injectable hydrogels have attracted much interest in tissue engineering (TE) applications because of their controlled flowability, adaptability, and easy handling properties. This work emphasizes the synthesis and characterizations of bioactive glass (BAG) nanoparticle-reinforced poly(ethylene glycol) (PEG)- and poly(N-vinylcarbazole) (pNVC)-based minimally invasive composite injectable hydrogel suitable for bone regeneration. First, the copolymer was synthesized from a combination of PEG and pNVC through reversible addition-fragmentation chain-transfer (RAFT) polymerization and nanocomposite hydrogel constructs were subsequently prepared by conjugating BAG particles at varying loading concentrations. Gel permeation chromatography (GPC) analysis confirmed the controlled nature of the polymer. Various physicochemical characterization results confirmed the successful synthesis of copolymer and nanocomposite hydrogels that showed good gelling and injectability properties. Our optimal nanocomposite hydrogel formulation showed excellent swelling properties in comparison to the copolymeric hydrogel due to the presence of hydrophilic BAG particles. The bone cell proliferation rate was found to be evidently higher in the nanocomposite hydrogel than in the copolymeric hydrogel. Moreover, the enhanced level of ALP activity and apatite mineralization for the nanocomposite in comparison to that for the copolymeric hydrogel indicates accelerated in vitro osteogenesis. Overall, our study findings indicate BAG particle-conjugated nanocomposite hydrogels can be used as promising grafting materials in orthopedic reconstructive surgeries complementary to conventional bone graft substitutes in cancellous bone defects due to their 3D porous framework, minimal invasiveness, and ability to form any desired shape to match irregular bone defects.

Onion-like doxorubicin-carrying polymeric nanomicelles with tumor acidity-sensitive dePEGylation to expose positively-charged chitosan shell for enhanced cancer chemotherapy.

To effectively promote antitumor potency of doxorubicin (DOX), a regularly used chemotherapy drug, the tumor acidity-responsive polymeric nanomicelles from self-assembly of the as-synthesized amphiphilic benzoic imine-containing PEGylated chitosan-g-poly(lactic-co-glycolic acid) (PLGA) conjugates were developed as vehicles of DOX. The attained PEGylated chitosan-g-PLGA nanomicelles with high PEGylation degree (H-PEG-CSPNs) were characterized to exhibit a "onion-like" core-shell-corona structure consisting of a hydrophobic PLGA core covered by benzoic imine-rich chitosan shell and outer hydrophilic PEG corona. The DOX-carrying H-PEG-CSPNs (DOX@H-PEG-CSPNs) displayed robust colloidal stability under large-volume dilution condition and in a serum-containing aqueous solution of physiological salt concentration. Importantly, the DOX@H-PEG-CSPNs in weak acidic milieu undergoing the hydrolysis of benzoic imine bonds and increased protonation of chitosan shell showed dePEGylation and surface charge conversion. Also, the considerable swelling of protonated chitosan shell within DOX@H-PEG-CSPNs accelerated drug release. Notably, the cellular internalization of DOX@H-PEG-CSPNs by TRAMP-C1 prostate cancer cells under mimic acidic tumor microenvironment was efficiently boosted upon acidity-triggered detachment of PEG corona and exposure of positively-charged chitosan shell, thus augmenting DOX-mediated anticancer effect. Compared to free DOX molecules, the DOX@H-PEG-CSPNs appreciably suppressed TRAMP-C1 tumor growth in vivo, thereby showing great promise in improving DOX chemotherapy.