Self-assembled Nanoparticles Research Articles

Amino Acid-Derived Supramolecular Assembly and Soft Materials.

Amino acids (AAs), serving as the primary monomer of peptides and proteins, are widely present in nature. Benefiting from their inherent advantages, such as chemical diversity, low cost, ease of modification, chirality, biosafety, and bio-absorbability, AAs have been extensively exploited to create self-assembled nanostructures and supramolecular soft materials. In this review article, we systematically describe the recent progress regarding amino acid-derived assembly and functional soft materials. A brief background and several classified assemblies of AAs and their derivatives (chemically modified AAs) are summarized. The key non-covalent interactions to drive the assembly of AAs are emphasized based on the reported systems of self-assembled and co-assembled AAs. We discuss the molecular design of AAs and the general rules behind the hierarchical nanostructures. The resulting soft materials with interesting properties and potential applications are demonstrated. The conclusion and remarks on AA-based supramolecular assemblies are also presented from the viewpoint of chemistry, materials, and bio-applications.

Self-assembling nanoparticle engineered from the ferritinophagy complex as a rabies virus vaccine candidate

Over the past decade, there has been a growing interest in ferritin-based vaccines due to their enhanced antigen immunogenicity and favorable safety profiles, with several vaccine candidates targeting various pathogens advancing to phase I clinical trials. Nevertheless, challenges associated with particle heterogeneity, improper assembly and unanticipated immunogenicity due to the bulky protein adaptor have impeded further advancement. To overcome these challenges, we devise a universal ferritin-adaptor delivery platform based on structural insights derived from the natural ferritinophagy complex of the human ferritin heavy chain (FTH1) and the nuclear receptor coactivator 4 (NCOA4). The engineered ferritinophagy (Fagy)-tag peptide demonstrate significantly enhanced binding affinity to the 24-mer ferritin nanoparticle, enabling efficient antigen presentation. Subsequently, we construct a self-assembling rabies virus (RABV) vaccine candidate by noncovalently conjugating the Fagy-tagged glycoprotein domain III (GDIII) of RABV to the ferritin nanoparticle, maintaining superior homogeneity, stability and immunogenicity. This vaccine candidate induces potent, rapid, and durable immune responses, and protects female mice against the authentic RABV challenge after single-dose administration. Furthermore, this universal, ferritin-based antigen conjugating strategy offers significant potential for developing vaccine against diverse pathogens and diseases.

In vivo self-assembled albumin nanoparticle elicit antitumor immunity of PD-1 inhibitor by imaging and clearing tumor-associated macrophages.

Eliciting anti-tumor immune responses and improving the tumor microenvironment crucial for boosting the effectiveness of anti-PD-1 immunotherapy. Tumor-associated macrophages (TAMs), the primary types of immune cells infiltrating tumors, play a critical role in the formation of an immunosuppressive microenvironment. In this study, we constructed a novel Evans Blue (EB)-based in vivo self-assembled nanocarrier system, mUNO-EB-ICG-Fc@Alb nanoparticles (designated as MA NPs), for targeted imaging and clearance of M2-TAMs to elicit antitumor immunotherapy of PD-1 inhibitor. In vitro experiments demonstrated the specific fluorescence imaging and killing effect of MA NPs on M2-TAMs. In vivo experiments shown that MA NPs-induced chemodynamic therapy (CDT) successfully reversed the tumor immunosuppressive microenvironment (ITM), promoted intratumoral infiltration of T lymphocytes, and ultimately enhancing the anti-tumor immunotherapy effect of PD-1 inhibitors. This study might provide good inspiration for improving the therapeutic efficacy of cancer immunotherapy.

Development of oral pH-sensitive redox nanotherapeutics for gastric ulcer therapy

Gastric ulcer is a common gastrointestinal disorder worldwide. Although its pathogenesis is unclear, the overproduction of reactive oxygen species (ROS), which results in an oxidative imbalance, has been reported as a central driving mechanism. Within the scope of this investigation, we developed two different self-assembling redox nanoparticles (RNPs) with ROS-scavenging features for the oral treatment of gastric ulcers. One of them, referred to as RNPN, disintegrates in response to acidic pH, whereas the other, denoted as RNPO, remains intact regardless of pH variations. Both types of RNPs showed different free radical scavenging activities in vitro. Protonation of the amino linkages in the side chains of RNPN caused the micelle structure to collapse and the nitroxide radicals encapsulated in the core were exposed to the outside, resulting in a significant increase in antioxidant capacity as the pH decreases. In contrast, RNPO maintained its spherical structure and consistent antioxidant reactivity irrespective of pH changes. The in vivo gastric retention of orally administered RNPN was significantly improved compared to that of RNPO which might be explained by the increased exposure of cationic protonating segments in RNPN on the negatively charged gastric mucosal surface. Owing to its improved gastric retention and enhanced ROS scavenging capacity under acidic pH conditions, RNPN exhibited superior protective effects against oxidative stress induced by aspirin in a gastric ulcer mouse model compared to RNPO. In addition, neither RNPN nor RNPO resulted in severe lethal effects or significant changes in the morphology of zebrafish embryos, indicating their biosafety. Our results suggest that the oral administration of RNPs has a high therapeutic potential for gastric ulcer treatment.

Extreme Electron-Photon Interaction in Disordered Perovskites.

The interaction of light with solids can be dramatically enhanced owing to electron-photon momentum matching. This mechanism manifests when light scattering from nanometer-sized clusters including a specific case of self-assembled nanostructures that form a long-range translational order but local disorder (crystal-liquid duality). In this paper, a new strategy based on both cases for the light-matter-interaction enhancement in a direct bandgap semiconductor - lead halide perovskite CsPbBr3 - by using electric pulse-driven structural disorder, is addressed. The disordered state allows the generation of confined photons, and the formation of an electronic continuum of static/dynamic defect states across the forbidden gap (Urbach bridge). Both mechanisms underlie photon-momentum-enabled electronic Raman scattering (ERS) and single-photon anti-Stokes photoluminescence (PL) under sub-band pump. PL/ERS blinking is discussed to be associated with thermal fluctuations of cross-linked [PbBr6]4- octahedra. Time-delayed synchronization of PL/ERS blinking causes enhanced spontaneous emission at room temperature. These findings indicate the role of photon momentum in enhanced light-matter interactions in disordered and nanostructured solids.

Differences in the permeation of Licoricchalcone A-polysaccharide self-assembled nanoparticles on healthy and DNCB-induced atopic dermatitis in Balb/c mice

Nanoformulation have been widely used in skin and transdermal drug delivery. However, the differences in integral nanoparticles absorption in healthy and diseased skin have not yet fully analyzed. The present study attempted to explore the percutaneous absorption of drugs via lesional skin by using atopic dermatitis (AD) as a model, dinitrochlorobenzene (DNCB) induced AD-like skin. In here, the small molecules of insoluble Licoricchalcone A (LA) and macromolecules glycyrrhizin polysaccharide were used to prepare LA-polysaccharide self-assembled nanoparticles (GPA-SANs) by micro-precipitation. An environment-responsive dye, P4, was loaded into SAN to track the transdermal translocation of the nanoparticles, while the drug marked with coumarin 6 (C6). Compared to healthy skin, the permeability of GPA-SANs on AD-like skin is stronger, which may be due to damage to the stratum corneum of the AD-like skin and increased intercellular spaces, resulting in an increased permeability coefficient. Therefore, the storage of nanoparticles and their diffusion at the lesion site also increased accordingly. CLSM shown that the fluorescence of P4 and C6 is observed to concentrate around the hair follicles and disseminate in the surrounding area in both AD-affected and healthy skin.It can be clearly seen that fluorescence signal of C6 in the intercellular spaces of the dermis and epidermis of AD-like skin, indicating that nano-drug on the disease skin can penetrate through the intercellular pathway to achieve therapeutic. The focus of the present study is to assess the permeability of healthy and disease skin, discuss their characteristics and discrepancy, aiming to provide a reference for the further study of nano-formulations in transdermal delivery.

Self-assembled nanoparticles of PEG and poly(2-oxazoline) based lactide block copolymers

Access to self-assembled nanoparticles has become increasingly vital for the development of next generation adjuvants for the delivery of nucleic acid therapeutics. However, the block ratio of amphiphilic block copolymers plays a significant role in achieving the desired architectures and in some cases coformulation of two different block copolymers is needed. Herein, we introduce an elegant approach to self-assembled stomatocytes and cubosomes through coformulation of PEG and poly(2-oxazoline) (POx) based lactide diblock copolymers. A series of well-defined POx macroinitiators and their block copolymers with D,L-lactide (PDLLA) has been synthesized and achieved narrow polydispersity indices at high monomer conversions. Thermal analysis of block copolymers indicated tunable glass transition temperatures (Tg) ranging from 33 °C to 56 °C. Other critical factors influencing the structure of the nanoparticle included the ratio of POx-PDLLA and PEG-PDLLA blocks as well as the hydrophobicity of the POx block. Moreover, DLS and cryo-TEM analysis revealed the formation of diverse nanostructures, namely stomatocytes, pseudo-vesicles, and possibly cubosomes. This versatile platform allows for precise control over nanoparticle shapes by adjusting block lengths and coformulation ratios. This highlights the potential of using coformulations in biomedical applications, enabling the rational design of advanced nanomaterials with tailored functionalities for specific targets.

RGD-based self-assembling nanodrugs for improved tumor therapy.

RGD-based self-assembling nanodrugs are a promising advancement in targeted cancer therapy, combining the specificity of RGD peptides with the benefits of nanotechnology. These nanodrugs enhance tumor targeting and cellular uptake while reducing off-target effects. RGD peptides facilitate the self-assembly of stable nanostructures, ensuring efficient drug delivery. Despite their potential, challenges such as immunogenicity, stability, tumor heterogeneity, and manufacturing scalability need to be addressed. Future research should focus on improving biocompatibility, advanced targeting strategies, personalized medicine approaches, and innovative manufacturing techniques. Overcoming these challenges will pave the way for the successful clinical translation of RGD-based nanodrugs, offering more effective and safer cancer treatments.

Application of stealth nanobeacon for traceability assurance in pharmaceutical tablets via surface-enhanced Raman scattering during the tablet coating process

Microtaggant technologies for on-dose authentication have garnered significant interest for use in the anti-counterfeit activities and traceability of pharmaceutical dosage forms. Previously, we proposed a stealth nanobeacon (NB) comprising self-assembled colloidal gold nanoparticles with reporter molecules that demonstrated characteristic surface-enhanced Raman scattering (SERS) activity. However, the integration of such microtaggants into standard production lines remains underexplored. In this study, we demonstrate the incorporation of NB into tablet coatings using a simple mixing method with conventional coating solutions. Rapid and discernible SERS responses from the NB-coated tablets were observed in response to laser excitation at 785 nm for 0.1s, implying that it is an advanced and efficient method for counterfeit detection. In addition, the SERS intensity of NB increased with coating time, suggesting that NB can be used as a tracer for the real-time monitoring of coating thickness. Furthermore, NB-coated tablets were indistinguishable from NB-free tablets, even during colorimetric analysis. These results suggest that the NB possesses stealth properties and can be easily incorporated into counterfeit detection products.

Fabrication with magnetic-spin coating: Influence of magnetic-inertia energy ratio on gold-pickering ferrofluid droplet assembly morphology

Magnetic self-assembly of nanoparticles is a well-known technique for creating thin-film array-patterned functional microstructures. However, an uncontrollable hierarchical assembly formation of magnetically stimulated particles has hindered the desired formation of free-standing two-dimensional (2D) array patterns in thin-film layers. In this study, we proposed a fluidic shearing effect from spin coating to reduce magnetically stimulated particles’ disarrayed and complex chain formations, thus promoting linear array formations, even as the film becomes thinner. A series of tests were conducted on a gold-Pickering ferrofluid emulsion (GPFE) dispersed in 15.2 mPas aqueous polyvinyl alcohol (PVAh), which was subjected to varying spin speeds under magnetic setups such as single (SI), compound (CC), and concentric (CR). These setups were chosen to observe the influence of magnetic field strength and distribution on the generated pattern profile from microscopic binary images of the resulting thin films. The aim was to quantify the formed chain thickness (ChT), chain gaps (ChG), and chain lengths (ChL) to capture the morphology and geometrical features of the formed patterns. Our results showed that the quantified values of these profiles and their dimensionless relationships were significantly influenced by the ratio between the applied magnetic packing energy and the centrifugally controlled fluidic energy, QPD. This investigation showed that ChT/ChG for a corresponding QPD value is 98.6% the same for all configurations, and CR was the best setup going forward, as it yielded the lowest array quality defectivity of 14%. Therefore, we assert that this fabrication method offers flexibility, cost-effectiveness, and expandability in generating linear array patterns that contain graduating variability in grating order dimensions within a single cast that can serve efficiently as a substrate for biomolecules under enhanced Raman and Infrared spectroscopies.

Targeted NO-Releasing L-arginine-Induced Hesperetin Self-Assembled Nanoparticles for Ulcerative Colitis Intervention

Overproduction of reactive oxygen species (ROS) plays a crucial role in initiating and advancing ulcerative colitis (UC), and the persistent cycle between ROS and inflammation accelerates disease development. Therefore, developing strategies that can effectively scavenge ROS and provide targeted intervention is crucial for the management of UC. In this study, we synthesized natural carrier-free nanoparticles (HST-Arg NPs) using the Mannich reaction and π-π stacking for the intervention of UC. HST-Arg NPs are an oral formulation that exhibits good antioxidant capabilities and gastrointestinal stability. Benefiting from the negatively charged characteristics, HST-Arg NPs can specifically accumulate in positively charged inflamed regions of the colon. Furthermore, in the oxidative microenvironment of colonic inflammation, HST-Arg NPs respond to ROS by releasing nitric oxide (NO). In mice model of UC induced by dextran sulfate sodium (DSS), HST-Arg NPs significantly mitigated colonic injury by modulating oxidative stress, lowering pro-inflammatory cytokines, and repairing intestinal barrier integrity. In summary, this convenient and targeted oral nanoparticle can effectively scavenge ROS at the site of inflammation and achieve gas intervention, offering robust theoretical support for the development of subsequent oral formulations in related inflammatory interventions. Statement of significanceNanotechnology has been extensively explored in the biomedical field, but the application of natural carrier-free nanotechnology in this area remains relatively rare. In this study, we developed a natural nanoparticle system based on hesperetin (HST), L-arginine (L-Arg), and vanillin (VA) to scavenge ROS and alleviate inflammation. In the context of ulcerative colitis (UC), the synthesized nanoparticles exhibited excellent intervention effects, effectively protecting the colon from damage. Consequently, these nanoparticles provide a promising and precise nutritional intervention strategy by addressing both oxidative stress and inflammatory pathways simultaneously, demonstrating significant potential for application.

ROS-responsive glycol chitosan-linked prodrug nanoparticle as a nanoplatform for tumor chemo-photodynamic therapy

Herein, we designed and synthesized novel reactive oxygen species (ROS)-responsive glycol chitosan-doxorubicin (DOX) prodrug via a ROS-cleavable thioketal (TK) linker. The obtained GC-TK-DOX formed self-assembled nanoparticles of 312 nm in aqueous media. Photosensitizers zinc phthalocyanine (ZnPc)-loaded GC-TK-DOX (GC-TK-DOX/ZnPc) nanoparticles were fabricated by using a dialysis approach. The GC-TK-DOX and GC-TK-DOX/ZnPc nanoparticles were nearly spherical by transmission electron microscopy (TEM) observation. Under 660-nm laser irradiation, GC-TK-DOX/ZnPc could generate singlet oxygen. Further, GC-TK-DOX/ZnPc nanoparticles exhibited ROS-sensitive release of DOX and ZnPc in vitro. GC-TK-DOX/ZnPc with laser irradiation showed more drug uptake and higher cytotoxic effects than GC-TK-DOX/ZnPc without irradiation, free DOX and GC-TK-DOX in HeLa tumor cells. Overall, these findings suggested that GC-TK-DOX/ZnPc could be a promising nanoarchitecture for synergetic chemo-photodynamic therapy against tumors.

Structural Basis for Alternative Self-Assembly Pathways Leading to Different Human Immunodeficiency Virus Capsid-Like Nanoparticles.

The mechanisms that underlie the spontaneous and faithful assembly of virus particles are guiding the design of self-assembling protein-based nanostructures for biomedical or nanotechnological uses. In this study, the human immunodeficiency virus (HIV-1) capsid was used as a model to investigate what molecular feature(s) may determine whether a protein nanoparticle with the intended architecture, instead of an aberrant particle, will be self-assembled in vitro. Attempts of using the HIV-1 capsid protein CA for achieving in vitro the self-assembly of cone-shaped nanoparticles that contain CA hexamers and pentamers, similar to authentic viral capsids, had typically yielded hexamer-only tubular particles. We hypothesized that a reduction in the stability of a transient major assembly intermediate, a trimer of CA dimers (ToD), will increase the propensity of CA to assemble in vitro into cone-shaped particles instead of tubes. Certain amino acid substitutions at CA-CA interfaces strongly favored in vitro the assembly of cone-shaped nanoparticles that resembled authentic HIV-1 capsids. All-atom MD simulations indicated that ToDs formed by CA mutants with increased propensity for assembly into cone-shaped particles are destabilized relative to ToDs formed by wt CA or by another mutant that assembles into tubes. The results also indicated that ToD destabilization is mediated by conformational distortion of different CA-CA interfaces, which removes some interprotein interactions within the ToD. A model is proposed to rationalize the linkage between reduced ToD stability and increased propensity for the formation of CA pentamers during particle growth in vitro, favoring the assembly of cone-shaped HIV-1 capsid-like nanoparticles.

Enhanced oxygen evolution reaction activity of oxygen-deficient perovskite catalysts with A-site defects boosted by self-assembled silver nanoparticles

To enhance the competitiveness of perovskite electrocatalysts in oxygen evolution reaction (OER), it is vital to improve its catalytic activity and durability while controlling costs. Herein, we report a composite electrocatalyst of Ag/Sr0·8Ag0·2Co0·75Fe0·25O3-δ, which was designed by integrating internal structure-engineering, A-site defect, and in-situ Ag segregation. This electrocatalyst demonstrates an excellent OER performance in an alkaline electrolyte, surpassing the catalytic activity and durability of commercial RuO2 electrocatalysts. Various characterization techniques as well as density functional theory (DFT) calculations were performed to elucidate the synergistic coupling effects of Sr0·8Ag0·2Co0·75Fe0·25O3-δ with Ag nanoparticles (NPs) in the OER process. The robust interface anchoring Ag NPs on Sr0·8Ag0·2Co0·75Fe0·25O3-δ perovskite can induce ligand effects and interparticle cooperation, thereby promoting electron transfer and ion migration during OER. Meanwhile, partial Ag+ forms Ag NPs contributing to the formation of A-site defects, which results in an increase of oxygen vacancies and induces lattice expansion. A-site defects can optimize the occupancy of eg orbitals close to unity for B-site transition metals, thereby greatly enhancing OER catalytic activity. This work highlights an effective strategy to enhance OER activity of perovskite electrocatalysts.

EBSD and TKD analyses using inverted contrast Kikuchi diffraction patterns and alternative measurement geometries

Electron backscatter diffraction (EBSD) patterns can exhibit Kikuchi bands with inverted contrast due to anomalous absorption. This can be observed, for example, on samples with nanoscale topography, in case of a low tilt backscattering geometry, or for transmission Kikuchi diffraction (TKD) on thicker samples. Three examples are discussed where contrast-inverted physics-based simulated master patterns have been applied to find the correct crystal orientation. As first EBSD example, self-assembled gold nanostructures made of Au fcc and Au hcp phases on single-crystal germanium were investigated. Gold covered about 12% of the mapped area, with only two thirds being successfully interpreted using standard Hough-based indexing. The remaining third was solved by brute force indexing using a contrast-inverted master pattern. The second EBSD example deals with maps collected at a non-tilted surface instead of the commonly used 70° tilted one. As TKD example, a jet-polished foil made of duplex stainless steel 2205 was examined. The thin part close to the hole edge producing normal-contrast patterns were standard indexed. The areas of the foil that become thicker with increasing distance from the edge of the hole produce contrast-inverted patterns. They covered three times the evaluable area and were successfully processed using the contrast-inverted master pattern. In the last example, inverted patterns collected at a non-tiled sample were mathematically inverted to normal contrast, and Hough/Radon-based indexing was successfully applied.

Sustained therapeutic effects of self-assembled hyaluronic acid nanoparticles loaded with α-Ketoglutarate in various osteoarthritis stages

Osteoarthritis (OA) is a prevalent degenerative disease characterized by irreversible destruction of articular cartilage, for which no current drugs are known to modify its progression. While intra-articular (IA) injections of hyaluronic acid (HA) offer temporary relief, their effectiveness and long-term benefits are debated. Alpha-ketoglutarate (αKG) has potential chondroprotective properties, but its use is limited by a short half-life and poor cartilage-targeting efficiency. Here, we developed self-assembled HA-αKG nanoparticles (NPs) to combine the benefits of both HA and αKG, showing stability, bioavailability, and sustained pH-responsive release in the knee joint. In both early and advanced OA stages in mice, HA, αKG, and HA-αKG NPs could relieve pain, enhance mobility, and reduce cartilage damage, with HA-αKG NPs demonstrating the best efficacy. Mechanistically, αKG not only promotes cartilage matrix synthesis but also inhibits degradation by activating the PERK-ATF4 signaling pathway to reduce endoplasmic reticulum stress (ERS) in chondrocytes. This study highlights the therapeutic potential of HA-αKG NPs for treating various OA stages, with efficient and sustained effects, suggesting rapid clinical adoption and high acceptability among clinicians and patients.

Self-assembly and energy storage potentials of biphasic phase change azobenzene liquid crystalline block copolymers

Flexible polymeric materials with potentials in energy storage have attracted extensive attention in today's sustainable society. Here, we reported a series of crystalline-liquid crystalline biphasic phase change block copolymers, poly(ethylene oxide)-b-poly(11-(4-(4-cyanophenylazo)phenoxy)undecane methacrylate) (PEO-b-PMAAzo), and studied the UV and Li+ ions coordination-mediated self-assembly for the potentials in phase change energy storage and solid electrolytes. The PEO-b-PMAAzo BCPs possess both the solid-liquid phase transition of PEO and the photo-chemical-thermal energy transition of PMAAzo block. Meanwhile, PEO has the capability to coordinate with the Li+ for the ionic conductivity. We explored the binary phase change behaviors and thermal energy density of the BCPs with different lithium ion concentrations before and after UV irradiation. The addition of LiTFSI salts increases the interaction parameters (χ) of the BCPs leading to phase transition of the self-assembled nanostructures. The phase diagram covering LAM, HEX, GYR, Fddd and HPL nanostructures facilitating ion transport was demonstrated. The PMAAzo block enabled the solid feature of the BCPs and ensured the high energy density and high conductivity. This work demonstrates that the combination of the functional polymers in one BCP not only provides multiple morphology tunabilities but also enables multiple functionalities from energy conversation and storage to ionic conductive electrolytes.

Preparation, Evaluation, and Bioinformatics Study of Hyaluronic Acid-Modified Ginsenoside Rb1 Self-Assembled Nanoparticles for Treating Cardiovascular Diseases.

(1) Objective: To optimize the preparation process of hyaluronic acid-modified ginsenoside Rb1 self-assembled nanoparticles (HA@GRb1@CS NPs), characterize and evaluate them in vitro, and investigate the mechanism of action of HA@GRb1@CS NPs in treating cardiovascular diseases (CVDs) associated with inflammation and oxidative stress. (2) Methods: The optimal preparation process was screened through Plackett-Burman and Box-Behnken designs. Physical characterization of HA@GRb1@CS NPs was conducted using transmission electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry. Stability experiments, in vitro drug release studies, and lyophilisate selection were performed to evaluate the in vitro performance of HA@GRb1@CS NPs. The anti-inflammatory and antioxidant capabilities of HA@GRb1@CS NPs were assessed using H9c2 and RAW264.7 cells. Additionally, bioinformatics tools were employed to explore the mechanism of action of HA@GRb1@CS NPs in the treatment of CVDs associated with inflammation and oxidative stress. (3) Results: The optimal preparation process for HA@GRb1@CS NPs was achieved with a CS concentration of 2 mg/mL, a TPP concentration of 2.3 mg/mL, and a CS to TPP mass concentration ratio of 1.5:1, resulting in a particle size of 126.4 nm, a zeta potential of 36.8 mV, and a PDI of 0.243. Characterization studies confirmed successful encapsulation of the drug within the carrier, indicating successful preparation of HA@GRb1@CS NPs. In vitro evaluations demonstrated that HA@GRb1@CS NPs exhibited sustained-release effects, leading to reduced MDA (Malondialdehyde) content and increased SOD (Superoxide Dismutase) content in oxidatively damaged H9c2 cells. Furthermore, it showed enhanced DPPH (2,2-Diphenyl-1-picrylhydrazyl) and ABTS+ [2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)] free radical scavenging rates and inhibited the release of inflammatory factors NO (Nitric Oxide) and IL-6 (Interleukin-6) from RAW264.7 cells. (4) Conclusions: The HA@GRb1@CS NPs prepared in this study exhibit favorable properties with stable quality and significant anti-inflammatory and antioxidant capabilities. The mechanisms underlying their therapeutic effects on CVDs may involve targeting STAT3, JUN, EGFR, CASP3, and other pathways regulating cell apoptosis, autophagy, anti-lipid, and arterial sclerosis signaling pathways.

Gambogic acid and IR780 self-assembled nanoparticles for combined chemo-phototherapy

Combined chemo-phototherapy has shown considerable advantages and potential in cancer treatment. For this purpose, self-assembled nanoparticles by gambogic acid (GA) and IR780 (referred to as GA-IR780 NPs) were prepared. Herein, GA, an active compound derived from Garcinia hanburyi Hook.f, was selected as a chemo-agent. IR780 was used as a photothermal agent as well as a photosensitizer, which could kill tumor cells via photothermal effect and photodynamic effect. The obtained GA-IR780 NPs were uniform spheres with particle size of ca. 50 nm. The drug loading efficiency of GA and IR780 was 38.42 % and 56.64 %, respectively. The GA-IR780 NPs exhibited excellent photothermal properties as well as photodynamic effect when irradiated by near infrared (NIR) light (808 nm, 2.0 W/cm2). Moreover, the GA-IR780 NPs showed enhanced cytotoxicity with NIR light activation. Results of animal experiments showed that GA-IR780 NPs had the most significant tumor inhibition when irradiated by laser, and the results of H&E, Ki-67 and TUNEL staining confirmed that the GA-IR780 NPs+Laser group caused the most severe tumor tissue damage. The above results indicated that GA-mediated chemotherapy combining with IR780-based phototherapy could significantly improve the anti-tumor efficacy.

Exploring pH-Triggered Lamellar to Cubic Phase Transition in 2-Hydroxyoleic Acid/Monoolein Nanodispersions: Insights into Membrane Physicochemical Properties.

Self-assembled lipid nanoparticles (LNPs) are essential nanocarriers for drug delivery. Functionalization of LNPs with ionizable lipids creates pH-responsive nanoparticles that change structures under varying pH conditions, enabling pH-triggered drug release. Typically, bicontinuous cubic phase nanoparticles (Cubosomes) and lamellar structured vesicles (Liposomes) differ in lipid packing statuses, affecting drug release and cellular uptake. However, most research predominantly focuses on elucidating lattice structure changes of these LNPs without a deep investigation of lipid-membrane properties. Addressing this gap, our study delves into the lipid-membrane physicochemical property variations during the lamellar-to-cubic phase transition. Here, we prepared pH-responsive LNPs using 2-hydroxyoleic acid/monoolein (2-OHOA/MO) binary components. Small-angle X-ray scattering (SAXS) revealed a phase transition from lamellar vesicles (Lα) to cubosomes (Im3m/Pn3m) with pH reduction. Laurdan and 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescence probes tracked the lipid-water interfacial polarity and lipid-membrane fluidity variations during the phase transition. Raman spectroscopy provided further insights into lipid-membrane lipid chain packing and chain torsion. We observed that the changes in lipid-membrane properties coincided with the lamellar-to-cubic phase transition, emphasizing the interplay between the phase structure and lipid-membrane behaviors in the 2-OHOA/MO system. This study provides insights into the lipid-membrane properties variation during the pH-triggered phase transition in the 2-OHOA/MO system, guiding future research toward more effective and reliable pH-responsive drug delivery platforms.