Efficient Release Research Articles

Cationic Micelle-like Nanoparticles as the Carrier of Methotrexate for Glioblastoma Treatment

In the present study, ultra-small, magnetic, oleyl amine-coated Fe3O4 nanoparticles were synthesized and stabilized with a cationic ligand, cetyltrimethylammonium bromide, and an anticancer drug, methotrexate, was incorporated into a micelle-like nanoparticle structure for glioblastoma treatment. Nanoparticles were further characterized for their physicochemical properties using spectroscopic methods. Drug incorporation efficiency, drug loading, and drug release profile of the nanoparticles were investigated. According to the results, max incorporation efficiency% of 89.5 was found for 25 µg/mL of methotrexate-loaded nanoparticles. The cumulative amount of methotrexate released reached 40% at physiological pH and 85% at a pH of 5.0 up to 12 h. The toxicity and anticancer efficacy of the nanoparticles were also studied on U87 cancer and L929 cells. IC50 concentration of nanoparticles reduced cell viability to 49% in U87 and 72% in L929 cells. The cellular uptake of nanoparticles was found to be 1.92-fold higher in U87 than in L929 cells. The total apoptosis% in U87 cells was estimated to be ~10-fold higher than what was observed in the L929 cells. Nanoparticles also inhibited the cell motility and prevented the metastasis of U87 cell lines. Overall, designed nanoparticles are a promising controlled delivery system for methotrexate to the cancer cells to achieve better therapeutic outcomes.

RGD peptide-conjugated polydopamine nanoparticles loaded with doxorubicin for combined chemotherapy and photothermal therapy in thyroid cancer

ObjectiveTo construct polydopamine (PDA)-based nanoparticles (NPs) for combined chemotherapy (CT) and photothermal therapy (PTT) of thyroid tumors by conjugating doxorubicin (DOX) via Schiff base reaction and decorating with RGD peptide.MethodsPDA NPs were synthesized using dopamine hydrochloride (DA) as the raw material and reacted with DOX-PEG-NH2 to obtain PDA-DOX NPs. Subsequently, RGD peptide was coupled with PDA-DOX NPs for modification. Their size, charge, and shape were characterized using DLS and SEM. The assembly of DOX was verified by ultraviolet–visible spectroscopy (UV–Vis), and the release efficiency of DOX under different pH conditions was calculated. The antitumor effect of RGD@PDA-DOX was validated in KTC-1 cells and tumor-bearing nude mice.ResultsThe prepared RGD@PDA-DOX exhibited excellent dispersion, stability, and biocompatibility. PDA-DOX possessed superior photothermal conversion efficiency, capable of rapidly elevating the solution temperature within 5 min. In vitro studies revealed that the inhibitory rate of RGD@PDA-DOX combined with 808 nm laser on KTC-1 cells reached 92% (p < 0.05). In vivo experiments demonstrated that RGD@PDA-DOX exhibits no cytotoxicity. The modification with RGD peptides enables RGD@PDA-DOX to target tumor regions and accumulate over an extended period. Additionally, RGD@PDA-DOX, when combined with an 808 nm laser, significantly inhibits tumor growth.ConclusionRGD@PDA-DOX can effectively accumulate in tumor regions and demonstrates excellent anti-tumor efficacy. It may serve as a feasible approach for the effective treatment of thyroid tumors, providing further evidence and data for clinical translation.

Polymerizable Cholinium-Based Antibiotics for Polymer Carriers: Systems with Combined Load of Cloxacillin and Ampicillin

Single and dual-drug delivery systems (DDSs) based on linear choline polymers were designed through the controlled polymerization of a pharmaceutically functionalized monomer, i.e., [2-(methacryloyloxy)ethyl]trimethylammonium, with counterions of cloxacillin (TMAMA/CLX), or its copolymerization with [2-(methacryloyloxy)ethyl]trimethylammonium with ampicillin (TMAMA/AMP), providing antibiotic properties. This strategy was effective in attaining well-defined linear copolymers with 38–93 mol. % of TMAMA content, which were regulated by the initial ratio of TMAMA to methyl methacrylate comonomer. The polymer compositions were controlled by the total monomer conversion (40–75%), resulting in a variable degree of polymerization (DPn = 160–300) and pharmaceutical anion contents (CLX− 51–80% and AMP− 78–87%). In aqueous solution, the polymers formed particles with sizes ranging between 274 and 380 nm for CLX− systems and 288–348 nm for CLX−/AMP− systems. In vitro drug release, driven by the exchange of pharmaceutical anions with phosphate ions in phosphate-buffered saline (PBS), imitating a physiological fluid, demonstrated release efficiencies of 58–76% for CLX− (10.5–13.6 µg/mL) in single systems, and 91–100% for CLX− (12.9–15.1 µg/mL) and 97–100% for AMP− (21.1–23.3 µg/mL) in dual systems. Compared to conventional systems delivering antibiotics without a polymer carrier, the choline-based polymer DDS attained satisfactory levels of drug loading content and (co-)release from the polymer carriers, offering a promising alternative for antibiotic delivery.

Composite Structure MgB2@KNO3 With Multi-Effect Synergies to Improve Combustion Performance and Energy Release of B

ABSTRACT With the deepening of research, boron compounds have gradually gained favor among researchers due to their high calorific value and excellent ignition and combustion performance. In this paper, MgB2@KNO3, which exhibits excellent ignition and combustion properties, was synthesized using ultrasonic dispersion and magnetic stirring. The improved ignition mechanism and energy release characteristics of MgB2@KNO3 were elucidated using DSC/TG, SEM, EDS, XRD, and optical characterization, in conjunction with computational results from NASA-CEA. The surface activation energy and ignition energy of MgB2@KNO3 are 35.7% and 25%, respectively, lower than those of conventional B/KNO3 mixtures. Compared to the mixed sample of B/KNO3, the heat release of MgB2@KNO3 increased by 72.4%. The synergistic and effective interactions between oxygen, magnesium vapor, and boron in MgB2@KNO3 systems result in efficient energy release performance, making MgB2@KNO3 a promising material for use as a high-energy fuel in propellants, explosives, and pyrotechnic products.

A Pioneer Review on Lactoferrin-Conjugated Extracellular Nanovesicles for Targeting Cellular Melanoma: Recent Advancements and Future Prospects.

Melanoma, a highly aggressive form of skin cancer, presents a formidable challenge in terms of treatment due to its propensity for metastasis and resistance to conventional therapies. The development of innovative nanocarriers for targeted drug delivery has opened new avenues in cancer therapy. Lactoferrin-conjugated extracellular nanovesicles (LF-EVs) have emerged as a promising vehicle in the targeted treatment of cellular melanoma, owing to their natural biocompatibility, enhanced bioavailability, and ability to traverse biological barriers effectively. This review synthesizes recent advancements in the use of LF-EVs as a novel drug delivery system for melanoma, emphasizing their unique capacity to enhance cellular uptake through LF's receptor-mediated endocytosis pathways. Key studies demonstrate that LF conjugation significantly increases the specificity of extracellular nanovesicles for melanoma cells, minimizes off-target effects, and promotes efficient intracellular drug release. Furthermore, we explore how LF-EVs interact with the tumor microenvironment, potentially inhibiting melanoma progression and metastasis while supporting antitumor immune responses. Future prospects in this field include optimizing LF conjugation techniques, improving the scalability of LF-EV production, and integrating multifunctional payloads to target drug resistance mechanisms. This review highlights the potential of LF-EVs to transform melanoma treatment strategies, bridging current gaps in therapeutic delivery and paving the way for personalized and less invasive melanoma therapies.

A General "Two-Lock" Strategy to Enhance Drug Loading and Lysosomal Escape in Intelligent Boronate Ester Polymer Nanoparticles for Improved Chemotherapy.

Boronate ester can be used to prepare intelligent polymer nanoparticles (NPs). However, the traditional boronate ester polymer NPs made of boronic acid and diols using a "single-lock" strategy (B-O NPs) exhibit low drug loading capacity (DLC) and insufficient lysosomal escape ability, resulting in limited antitumor efficacy. We develop a "two-lock" strategy that combines dodecanamine and boronic acid using boron-nitrogen (B ← N) coordination to enhance the formation of a boronate ester polymer. Through this strategy, amphiphilic dextran and poly(vinyl alcohol) are synthesized through conjugation with the phenylboronic acid (PBA)/dodecanamine complex. The amphiphilic dextran encapsulates paclitaxel (PTX) to form B-N-O NPs with a higher DLC than their "single-lock" compartments due to enhanced boronate ester stability and improved hydrophobic drug-polymer interactions. Moreover, the B-N-O NPs release more PTX under acidic conditions compared with the B-O NPs. To demonstrate the generality of this "two-lock" strategy, eight polymer prodrug B-N-O NPs employing poly(vinyl alcohol) or dextran, along with PBA-modified gemcitabine, fluorouracil, and 7-ethyl-10-hydroxycamptothecin, or boronic acid-containing bortezomib and dodecanamine, are prepared, showing overall enhanced DLC and higher responsive drug release efficiency compared to B-O NPs. Importantly, B-N-O NPs with a combination of dodecanamine and boronic acid show a better lysosomal escape capability than B-O NPs. Moreover, B-N-O NPs exhibit stronger cytotoxicity compared to B-O NPs and free drugs in vitro. Their enhanced drug loading, responsive drug release, and lysosomal escape abilities contribute to enhanced antitumor efficacy in vivo. This "two-lock" strategy can be a general and convenient method to prepare responsive polymer NPs with enhanced anticancer efficacy.

Preparation and Characterization of Nanostructured Lipid Carriers (NLCs) Containing Glycyrrhiza glabra Extract for the Treatment of Skin Hyperpigmentation.

This study aimed to prepare, characterize, and in vitro and in vivo evaluate a novel nanostructured lipid carriers (NLCs) formulation containing two fractions of Glycyrrhiza glabra L. (licorice) extract for the treatment of hyperpigmentation. Two fractions, one enriched with glabridin (FEG) and the other enriched with liquiritin (FEL), were obtained by partitioning the methanol (MeOH) extract of licorice roots with ethyl acetate (EtOAc) and partitioning the EtOAc fraction with butanol (n-BuOH) and water. The quantities of glabridin (Glab) and liquiritin (LQ) in the fractions were determined by high-performance liquid chromatography (HPLC). FEG and FEL were loaded in different NLC formulations, and surface characterization and long-term stability were studied using Dynamic Light Scattering (DLS). The best formulation was chosen for further surface characterization, including Transmission Electron Microscopy (TEM), Differential Scanning Calorimetry (DSC), and Fouriertransform infrared (FTIR) spectroscopy. Moreover, entrapment efficiency percentage (EE%), in vitro drug release, in vivo skin penetration, cytotoxicity on B16F10 melanoma cells, effect on melanin production, and anti- tyrosinase activity were tested for the selected formulation. Based on HPLC results, FEG contained 34.501 mg/g of Glab, and FEL contained 31.714 mg/g of LQ. Among 20 different formulations, NLC 20 (LG-NLCs) showed desirable DLS results with a Z-average size of 185.3 ± 1.08 nm, polydispersity index (PDI) of 0.229 ± 0.35, and zeta potential of -16.2 ± 1.13 mV. It indicated good spherical shape, high EE% (79.01% for Glab and 69.27% for LQ), two-stage release pattern (an initial burst release followed by sustained release), efficient in vivo skin penetration, and strong anti-tyrosinase activity. LG-NLCs had acceptable physiochemical stability for up to 9 months and were non-cytotoxic. The LG-NLC formulation has revealed desirable surface characterization, good physiochemical stability, efficient drug release pattern and in vivo penetration, and high EE%. Therefore, it can be a suitable nanosystem for the delivery of licorice extract in the treatment of hyperpigmentation.

Designing of amiloride loaded citrate functionalized amorphous silica nanoparticles to investigate its genotoxic and cytotoxic potential

In the present work, silica-based nanocarrier for the anticancer drug, amiloride have been synthesized and characterized using various physicochemical techniques. The aim of this work emphasis on investigating the physicochemical properties and cytotoxic effects of citrate-functionalized amiloride loaded silica nanoparticles. Silica nanoparticles synthesis was carried out via condensation reaction, then coated by tris sodium citrate, followed by their functionalization using amiloride through EDC-NHS reaction. SEM and HR-XRD analysis indicated the formation of amorphous spherical silica nanoparticles. The existence of citrate coating was evident from FT-IR and TGA results, which were supported by DLS and zeta potential studies. The formation of amiloride conjugated citrate coated silica nanoparticles (SiNPs-Cit@Ami) was confirmed by the DLS, Zeta potential and UV-Visible spectroscopy. Size of SiNPs-Cit@Ami nanoparticles was found to be around 80nm using TEM. Additionally, these nanoparticles showed high loading efficiency and time-dependent release of amiloride. DNA binding studies were examined using UV–Visible, Fluorescence spectroscopic and Competitive fluorescence studies. The results indicate that SiNPs-Cit@Ami bind to Ct-DNA via minor groove binding mode. Furthermore, the cytotoxic effect of SiNPs-Cit@Ami on HepG2 cell lines was found to be higher than amiloride alone. Our findings suggest that SiNPs-Cit@Ami can be employed as a promising candidate for cancer mitigation.

Physically crosslinked chitosan/αβ–glycerophosphate hydrogels enhanced by surface-modified cyclodextrin: An efficient strategy for controlled drug release

This study reports physically crosslinked chitosan/αβ–glycerophosphate (CS/GP) hydrogels containing surface-modified cyclodextrin for efficient controlled drug release. Highly water-soluble β–cyclodextrin-grafted L–serine (CD–g–Ser) compounds were synthesized, and employed as an effective carrier of berberine hydrochloride (Ber) for CS/GP hydrogels. Various characterizations, including gelation time determination, scanning electron microscopy, and viscosity measurement, indicated that the introduction of CD–g–Ser led to increased crosslinking degree, improved temperature sensitivity, and shortened sol–gel phase transition time of the hydrogel. Meanwhile, the sustained release ability for Ber was achieved due to the hydrophobic association between cyclodextrin and Ber. It was observed that within 4 h, the hydrogel containing CD–g–Ser released 40 % of Ber, while the CS/GP hydrogel without CD–g–Ser released 65 % of Ber. Furthermore, in vitro bacteriostasis experiments confirmed the drug-loaded hydrogel had an excellent antibacterial effect against E. coli and S. aureus (diameter of the inhibition zone up to (16.4 and 34.7) mm, respectively), low hemolysis rate (<2 %), and high cell viability (>90 %). The findings indicate that the physical crosslinked CS hydrogel can be used as a new drug delivery system, and its excellent antibacterial effect makes it a potential wound dressing candidate.

Optimization and performance evaluation of a novel nano-zeolite amended pure oxygen-driven membrane aerated biofilm reactor (Z-PO-MABR) for enhanced carbon and nitrogen removal from high-strength wastewater

High-strength wastewater presents significant environmental challenges. Membrane-aerated biofilm reactor (MABR) technology, enhanced by pure oxygen, improves treatment efficiency. Additionally, nano-zeolite-based techniques have shown promise. This study introduces a novel nano-zeolite amended pure oxygen-based MABR system (Z-PO-MABR), combining the benefits of pure oxygen and nano-zeolite. A bench-scale Z-PO-MABR was developed and tested under various conditions to optimize the operation. Optimization achieved high removal rates of organic carbon (98 %) and total nitrogen (96.9 %) with 72 g/Lr of nano-zeolite after 9 h. The Z-PO-MABR system outperforms conventional and pure oxygen-based MABRs, demonstrating greater efficiency in continuous and batch flow modes. The optimized parameters maximize carbon degradation and support microbial growth, offering an eco-sustainable solution for high-strength wastewater treatment. The Z-PO-MABR system is proposed as a promising method for efficient carbon removal and complete nitrogen release. Thus, the study strongly nominates the Z-PO-MABR as an effective treatment system.

Modulation of starch-based film properties for encapsulation of microbial inoculant

Controlled release of beneficial microorganisms in agriculture by encapsulation in biopolymeric matrices can improve biofertilizer efficacy, but it requires the modulation of properties to ensure more efficient and predictable release patterns. This study investigated the effect of a starch-based system to protect and release Priestia megaterium (former Bacillus megaterium) processed as films modified with potential cell-protective additives (maltodextrin, cellulose, and bentonite). The release kinetics, physicochemical and morphological film characteristics, and their protection against UV (Ultraviolet) radiation and temperature were evaluated. The microorganism release was dependent of the film microstructure and composition, both in initial and extended-release rates. Maltodextrin incorporation increased cell release, while cellulose and bentonite delayed due to influences in the water uptake (swelling) and diffusion across polymer structure. Modified films protected the microorganisms against UV radiation and extreme temperatures, being the film with all additives (SMCB) the best protective formulation (100 % UVC survival) compared to starch matrix (< 20 % UVC survival after 40 min) and the one with the highest viability at higher (54 % survival at 45 °C) and lower (80 % survival at 15 °C) temperatures. These insights pave the way for targeted, efficient, and sustainable biological solutions to agricultural practices, aligning with evolving needs in modern agriculture.

Preparation and Optimization of Gemcitabine Loaded PLGA Nanoparticle Using Box-Behnken Design for Targeting to Brain: In Vitro Characterization, Cytotoxicity and Apoptosis Study

Background: Treatment of glioma with conventional approaches remains a far-reaching target to provide the desired outcome. This study aimed to develop and optimize Gemcitabine hydrochloride- loaded PLGA nanoparticles (GNPs) using the Box-Behnken design methodology. The independent variables chosen for this study included the quantity of Polymer (PLGA) (X1), Tween 80 (X2), and Sonication time (X3), whereas the dependent variables were Particle size (Y1) EE % (Y2) and PDI (Y3). The optimized biodegradable nanoparticles were investigated for their anticancer effectiveness in U87MG human glioblastoma cells in vitro. Method: The formulation process involved two steps. Initially, emulsification was carried out by combining the organic polymer solution with the aqueous surfactant solution. Subsequently, in the second step, the organic solvent was evaporated, resulting in the precipitation of the polymer and the formation of nanoparticles. The quantity of PLGA, Tween 80, and PVA (at a constant concentration) was adjusted based on the experimental trial approach. Subsequently, the PLGA-based nanoparticles underwent characterization, wherein their particle size, encapsulation efficiency, polydispersity index (PDI), and cumulative release were assessed. The optimal formulation composition was determined as 200 mg of PLGA, 4 ml of Tween 80, and 2 mg of PVA. Further, the optimized GNPs were evaluated for their anti-cancer effectiveness on U87 MG cells by MTT and apoptosis assay. Results: The results demonstrated that the optimized GNPs exhibited an encapsulation efficiency of 81.66 %, a particle size of 140.1 nm, and a PDI of 0.37. The morphology of the Opt-GNPs was observed to be spherical through transmission electron microscopy (TEM). Conclusion: The Apoptosis study further confirmed the observations of MTT assay as the Opt- GNPs significantly enhanced the apoptosis in U-87 MG cells than the Standard marketed formulation.

Assessment of immunogenicity and protective efficiency of multi-epitope antigen-loaded in mannan decorated PLGA nanoparticles against tuberculosis

The antigen-targeting to dendritic cells (DCs) has gained increasing attention as the potential approach for immunotherapy in recent years due to the ability of DCs to regulate innate and adaptive immunity. In the present study, the immunogenicity and protective efficiency of mannan-decorated PLGA nanoparticles (NPs) loaded with multi-epitopes mycobacterium tuberculosis antigen (HspX-Ppe44-EsxV) were evaluated as a targeted delivery system to DCs. For this purpose, PLGA nanoparticle formulations were prepared and subsequently decorated by mannan. The physicochemical properties and level of mannan incorporation, as well as encapsulation efficiency and antigen release, were assessed. The potential of formulated NPs for antigen targeting to DCs, and immunogenicity against tuberculosis (TB) were investigated using immunofluorescence assay and in-vivo experiments. Mannan incorporation enhanced the uptake of fusion-loaded PLGA by DCs. The cytokine and antibody assays demonstrated that mannosylation of NPs and BCG-primed mice boosted by mannan-PLGA could significantly elevate Th1-biased immune responses relative to the BCG and non-modified PLGA NPs. Our findings also proved that the mannosylated vaccine in the presence of CpG could evoke Th1 and Th17 responses with appropriate protective efficiency against TB in mice. This result illustrated that the active targeting of DCs by mannan-PLGA NPs could induce a proper anti-tuberculosis response, which is essential for protection against tuberculosis.

MP-based plant oleogels structuring with various unsaturated oil: Fabrication, characterization, and in-vitro digestion.

Recently, research on the plant-based oleogels, has gained significant attention as a promising approach for oil formulation. In this research, emulsion-templated technique utilizing millet prolamin (MP) as oleogelator was employed for crafting edible oleogels from various vegetable oils of varying degree of unsaturation. The focus of the study was to examine the formation process, structural characteristics, rheological properties, and lipid digestion of these oleogels. The results indicated that MP-based oleogels exhibited uniform morphology and low oil loss. The construction of the oleogel network could be attributed to hydrogen bonding between oleogelator molecules, hydrophobic interactions among the oleogelator molecules and between the oleogelator and oil, as well as van der Waals forces between the oil molecules themselves. Increasing MP concentration formed a denser oleogel network, and exhibited greater elastic moduli (G') and viscous moduli (G''). Additionally, 8% MP oleogel prepared from flaxseed oil with high linolenic acid showed low oil loss, high hardness and efficient release of free fatty acids. These results indicated the potential of MP as an oleogelator in creating oleogels, and it is promising for fabricating trans-free and low-saturated oleogel-based products.

Zein/chitosan Janus film incorporated with tannic acid and cinnamon essential oil co-loaded Pickering emulsion for sustained controlled release and pork preservation.

The development of active packaging offers a promising approach to reducing food waste. However, challenges remain, particularly in achieving efficient release dynamics of active compounds and balancing the barrier properties. Herein, a Janus structure zein/chitosan film is custom designed by layer-by-layer casting method to achieve sustainable and unidirectional release performance of antimicrobial agent, which comprises an inner loading layer of tannic acid (TA) and cinnamon essential oil (CEO) co-loaded Pickering emulsion incorporated with chitosan and an outer barrier layer of zein. The good interfacial compatibility between the entities of Pickering emulsion/chitosan loading layer and zein barrier layer had be confirmed via physicochemical structure characterization. The lower swelling rate of Pickering emulsion/chitosan film (47.61 %-51.71 %) indicated the sustained and stable release rate of substances from the inner loading layer, while the zein barrier layer restricted the diffusion of active molecules due to the high swelling rate (162.52 %). In addition, the films showed excellent antimicrobial activity (>99 % against key foodborne pathogens) and radical scavenging activity (2.5-fold enhancement). Moreover, the film loading layer showed predominantly controlled by a quasi-Fickian diffusion, and prolonged the shelf life of pork by 6 days under the unidirectional sustained release. Our work presents a promising fabrication strategy of antimicrobial packaging film with sustainable release performance for food preservation.

Coatomer complex I is required for the transport of SARS-CoV-2 progeny virions from the endoplasmic reticulum-Golgi intermediate compartment.

SARS-CoV-2 virions are synthesized within the ERGIC and are transported to the cell surface via vesicular transport for release. However, the precise mechanisms remain unclear. Through various electron microscopic techniques, we identified the presence of COPI on virion-transporting vesicles. Alterations in the distribution of COPI and ERGIC in SARS-CoV-2 infected cells are evident, suggesting their involvement in virus replication. When COPB2, a component of COPI, is depleted, progeny virions become trapped within the ERGIC, leading to a reduction in the efficiency of virion release. These findings highlight COPI's crucial role in mediating SARS-CoV-2 vesicular transport from the ERGIC and suggest it as a potential antiviral target.

Probing Different Lengths of the Tertiary Amine Head Group on Triglyceride-Mimetic Ionizable Lipid-Mediated siRNA Delivery.

Lipid nanoparticles (LNPs) have been utilized to deliver small interfering RNA (siRNA) to treat acute liver injury. However, LNPs exhibit suboptimal lysosomal escape capabilities and biodegradability. To address these limitations, we have designed triglyceride-mimetic ionizable lipids by conjugating N,N-dimethyl tertiary amine head groups to the sn-2 position of triglyceride (TG) through ester bonds. These ionizable lipids were abbreviated as 2C-TG, 3C-TG, and 4C-TG, with N,N-dimethyl tertiary amine head groups located in the β-, γ-, and δ-positions of the ester linkage bond, respectively. The uniform-size LNPs were prepared by using the ethanol dilution method. Notably, the position of the tertiary amine head group within the carbon chain of triglyceride-mimetic ionizable lipids is found to significantly influence critical parameters, including the encapsulation rate, pKa, cellular uptake, lysosomal escape, lipase release, and gene silencing efficiency. Our findings hold promise for improving the efficacy and safety of LNP-based siRNA therapeutics.

Surface-modified dendrimer nanoconjugate for targeting delivery of rifampicin

ObjectiveThe study aimed to formulate and evaluate the efficiency of surface-modified Polyamidoamine dendrimer (PAMAM) as a targeted nanocarrier for the antimycobacterial agent rifampicin. MethodsThe periphery of dendrimer was modified with mannose using α-D-mannopyranosylphenyl isothiocyanate and characterized using analytical techniques i.e., infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (NMR). Then, rifampicin was encapsulated into mannosylated dendrimers and evaluated for size, shape, encapsulation efficiency (EE%), drug-dendrimer interaction, and drug release. The toxicity of the nanoconjugates were assessed towards macrophages using the MTT technique. The study investigated the internalization of dendrimer nanoparticles into macrophages to assess the impact of mannose conjugation. Dendrimers were fluorescently labelled and the internalization was quantified using a fluorescence spectroscopy and flow cytometer methods. ResultsMannosylated dendrimers with different mannose densities were successfully developed. The nanoparticles were within the nanoscopic scale. The dendrimers appeared spheroidal under scanning electron microscopy (SEM), and thermal analysis confirmed the conjugation of rifampicin into the dendrimers. The nanoparticles exhibited a good EE% for rifampicin at 10.34 % w/w. After surface mannosylation, the EE% further increased, ranging from 43.43 % to 57.91 % w/w. Mannose-functionalized dendrimers prolonged rifampicin release in physiological pH, while a rapid release in pH 4.5 medium was noticed. The cytotoxicity of the dendrimers in RAW macrophages was considerably reduced after mannose functionalization. In vitro studies indicated that mannose significantly increased the macrophage uptake of nanoconjugates, likely via lectin receptor-mediated endocytosis. ConclusionOverall results suggested mannosylated dendrimers as an effective targeted pulmonary delivery system for rifampicin with negligible cytotoxicity.

PD-L1 antibody conjugated dihydrotanshinone I-loaded polymeric nanoparticle for targeted cancer immunotherapy combining PD-L1 blockade with immunogenic cell death

PurposeCombination immune checkpoint inhibitors (ICI) with chemotherapeutic agents has proven to be highly promising in cancer therapy. However, low response rate, immune-related adverse events, and lack of effectively targeted co-delivery strategy are still major hurdles to overcome for this combination therapeutic regimen. Herein, programmed death-L1 (PD-L1) antibody modified and dihydrotanshinone I (DHT) loaded nanoparticle was prepared for tumor targeting drug delivery, thus achieving immune checkpoint blockade (ICB) and immunogenic cell death (ICD) synergistic anti-tumor effects. MethodsThe DHT-loaded nanoparticle (DHT NP) was prepared by the emulsion solvent diffusion method. Atezolizumab (ATEZO) was thiolated with 2-iminothiolane and conjugated to the surface of DHT NP to prepare the ATEZO DHT NP. The drug encapsulation efficiency, drug loading, particle size and drug release were determined. The in vitro cellular uptake, cell proliferation inhibition and apoptosis were evaluated on the HGC-27 tumor cell. The in vivo tumor targeting, anti-tumor efficiency and immune regulation were assessed on tumor bearing mice. ResultsThe optimized ATEZO DHT NP was a spherical nanoparticle of about 250 nm with a continuous drug release profile. It was selectively taken up by the tumor cells through PD-L1 receptor-mediated endocytosis, which resulted in enhanced cytotoxicity and cell apoptosis. In vivo imaging further demonstrated its superior tumor tissue targeting ability. When tumor bearing mice were treated with the ATEZO DHT NP, its synergistic anti-tumor effect was much stronger than that of a single drug. Moreover, the tumor targeting delivery of DHT caused tumor necrosis and initiated ICD with release of tumor-associated antigens, which efficiently up-regulated the population of CD4+ and CD8+ T cells. Notably, there were no obvious system toxicity or tissue damage occur during the whole treatment period. ConclusionThe ATEZO DHT NP could specifically target to tumor and enhance treatment efficiency through combination of PD-L1 blockade with ICD effect.

Optically controlled phase change wood for energy storage and heat release

Molecular solar thermal (MOST) fuels efficiently store solar energy and release it as heat by photoisomerization-induced phase change. However, MOSTs still struggle to meet practical demands due to its slow cis-trans isomerization rate, solvent-assisted charging and low energy storage density. Herein, we develop an optically controlled phase change wood (OCPCW) through impregnating methoxyazobenzene (mAZO) into delignified basswood with light energy storage and thermal energy release. Wood, as supporting frame, accelerates the rate of cis-trans isomerization due to the dispersion of mAZO by wood pores. In addition, the per unit storage energy density of mAZO in OCPCW can reach 307.5 J·g−1, which is higher than that of pure mAZO (229 J·g−1), due to the hydrogen bonding between cellulose and mAZO. Under sunlight irradiation, the cis-OCPCM undergoes isomerization to trans-OCPCM, releasing heat and leading to a temperature increase approximately 2 °C higher than that of delignified basswood under identical conditions. Furthermore, color changing in response to phase change, the OCPCM could be designed for encrypted and decrypted information with dual imaging modes through the color change and exothermic behavior. This work paves the way for the development of phase change wood for efficient solar energy storage and release and application in encrypted information display.