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Bacteria can evade antimicrobial therapy by hiding inside host cells such as macrophages. Here we examine the ability of PLGA nanoparticles to deliver antibiotics to intracellular bacteria, specifically focusing upon the impact of nanoparticle size. Different sized Rhodamine-B conjugated PLGA nanoparticles were synthesized and uptake examined in two macrophage cell lines, as well as different epithelial cells, to determine the optimal properties for macrophage uptake. These studies demonstrate macrophages display a consistent increase in uptake with increased PLGA nanoparticle diameter. In a bacteria-macrophage co-culture model, we then examined the efficacy of different sized antibiotic-loaded PLGA nanoparticles against intracellular infections with K. pneumoniae and S. aureus. Increasing the size of antibiotic-loaded PLGA nanoparticles significantly increased their potency against intracellular K. pneumoniae. However, this was not observed for S. aureus, potentially due to the observation these nanoparticles failed to access the compartment in which S. aureus reside. This work demonstrates for the first time that increasing the size of antibiotic-loaded PLGA nanoparticles can significantly enhance antimicrobial efficacy against K. pneumoniae intracellular macrophage infections. However, our S. aureus studies indicate this is not a 'one size fits all' approach for all intracellular infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Green processes for synthesizing nanocomposites are a hot area of research today as traditional processes are expensive, inefficient, harmful for synthesizing organic and inorganic molecules, and unsuitable for large-scale operations. The present study investigates the capacity of green synthesized Calcium oxide nanoparticles (CaO NPs) for efficiently removing Rhodamine B. Chemical reduction was replaced with Mulberry (Morus nigera) leaf extract as an environmentally friendly reaction mechanism. CaO NPs are characterized by various analytical techniques including EDX, BET, SEM, FTIR, TGA, Zeta Potential, Point of Zero Charge (PZC), and XRD. Maximum adsorption of Rhodamine B by CaO NPs is revealed at an initial concentration of Rhodamine B of 80 ppm, a temperature of 343 K, and contact time of 60 min, 0.4 g of adsorbent at a pH value of 7. Maximum removal of Rhodamine B by CaO NPs was found to be 98.2% which is promising with this small amount of adsorbent (0.4 g). Diverse Kinetic and adsorption isotherms are employed in this study to determine the requirement and significance of the adsorption process. Various adsorption isotherms such as Freundlich, Temkin, Dubinin-Radushkevich (D-R), and Langmuir models have been employed. Among the kinetic adsorption isotherms Elovich, Intraparticle kinetic model, pseudo 1st order, and pseudo 2nd order models were applied. The current study investigates the thorough understanding of the Rhodamine B adsorption process including the mechanism of adsorption using condition optimization, characterization, and model applications. The proposed adsorbent can be employed for the green removal of Rhodamine B from wastewater of industry with maximum efficiency and favorable regeneration properties., (© 2024. The Author(s).)

Contamination of water sources is a major environmental problem with far-reaching consequences for humanity. Organic substances are among the most widespread and persistent pollutants. Advanced oxidation processes, especially photocatalysis, have been considered as one of the most promising technologies for organic pollution control. In this study, hybrid photocatalysts based on N-doped TiO 2 , which exhibits activity in the visible region of the spectrum, and different content of octahedral Mo 6 bromide and iodide cluster complexes were synthesized to achieve the highest efficiency of the formed S-scheme photocatalytic system under white light irradiation. According to the data obtained, the resulting materials are nanoparticles with a diameter of ∼10 nm exhibiting absorption up to ∼550 nm. Photocatalytic studies were performed using model organic molecules - the more colored rhodamine B (RhB) and the less colored antibiotic tetracycline (TET). The most active samples showed high efficiencies against both pollutants with k eff ∼0.3-0.4 and 0.4-0.5 min -1 , respectively, while the activity of iodide complexes was ∼1.3 times higher than that of bromide complexes. The stability of the catalysts is preserved for up to 5 cycles of TET photodegradation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Oligonucleotide (ON) therapy is a promising treatment for a wide range of complex genetic disorders, but inefficient intracellular ON delivery has hindered clinical translation. Hollow silica nanoparticles (HSN) hold potential as effective ON delivery vehicles since ON can be encapsulated in the hollow core in situ where they are protected from degradation by eg nucleases. However, HSN must be modified to allow degradation and subsequent (sub)cellular ON release. In this report, we investigated the use of ion and fluorescent dye co-doping in the HSN silica matrix to enable HSN degradability and in vitro visualization., Methods: HSN were core encapsulated with ON, doped with Ca 2+ , Cu 2+ , Zn 2+ , Se 2+ and Sr 2+ ions and co-condensed with rhodamine b isothiocyanate (RITC) by a modified reverse microemulsion method. HSN were physiochemically characterized and their biological activity such as uptake and toxicity were evaluated in mesenchymal stem cells (hMSCs)., Results: We successfully doped HSN with RITC and Ca 2+ , Cu 2+ , Zn 2+ and Sr 2+ ions. We observed that doping HSN with Ca 2+ and Sr 2+ enhanced RITC incorporation while ON encapsulation in HSN increased Cu 2+ and Zn 2+ doping efficiency. Moreover, our dual-doped HSN demonstrated controlled ON release in the presence of intracellular mimicking levels of glutathione (GSH) and limited release in the absence of GSH over 14 days. HSN were biocompatible in hMSCs up to 300 µg/mL except for Cu 2+ doped HSNs which were cytotoxic even at ~10 µg/mL. HSN uptake was influenced by the dopant ion, DNA encapsulation, and HSN concentration, where Zn-HSN showed the lowest and Sr-HSN and Se-HSN D, the highest uptake in hMSCs., Conclusion: We report a straightforward one-pot procedure to create ion and fluorescent dye co-doped HSN that can efficiently incorporate ON, as promising new gene vectors., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (© 2024 Trayford et al.)

Energy conversion and pollutant degradation are critical for advancing sustainable technologies, yet they often encounter challenges related to charge recombination and efficiency limitations. This study explores iodine-doped TiO 2 nanoparticles as a potential solution for enhancing both energy conversion and pollutant degradation. The nanoparticles were synthesized via the sol-gel method with varying iodine precursor concentrations (0.025-0.1 M) and were characterized for their structural, compositional, and optical properties, particularly in relation to their photocatalytic performance in Rhodamine-B dye degradation. X-ray diffraction confirmed a tetragonal anatase crystal structure, with the average crystallite size decreasing from 10.06 nm to 8.82 nm with increase in iodine concentration. Selected area electron diffraction patterns verified the polycrystalline nature of the nanoparticles. Dynamic light scattering analysis showed hydrodynamic radii ranging from 95 to 125 nm. Fourier-transform infrared spectroscopy identified metal-oxygen vibrations at 441 cm⁻ 1 , and electron microscopy confirmed the spherical morphology of the nanoparticles. Elemental analysis detected the presence of Ti, O, and I in the samples. Diffuse reflectance spectroscopy indicated the optical absorption edges for the doped samples in the visible region from which the corresponding band gap values were deduced. Photoluminescence spectroscopy revealed that the sample with 0.1 M iodine exhibit the lowest emission intensity, suggesting reduced charge recombination. Notably, 0.1 M iodine doped TiO 2 samples demonstrated the highest photocatalytic efficiency, achieving 82.36% degradation of Rhodamine-B dye within 140 min under visible light. Additionally, ab-initio density functional theory calculations were performed to investigate the structural, optical, and adsorption properties of TiO 2 , iodine-doped TiO 2 , Rhodamine-B, and their composites, providing further insight into the enhanced photocatalytic activity observed in the experiments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Despite the necessity of the study of therapeutic drug monitoring of clonazepam (CLZ), there are only a few fast detection methods available for determining CLZ in biological media. This study aims to develop a cost-effective and ratiometric probe for the quantification of CLZ in plasma samples. Fluorescent polydopamine nanoparticles were produced through a self-polymerization process at a pH of 8.5. Rhodamine B molecules were employed as a fluorescent reference material, emitting stable fluorescence in the visible range. The fabricated probe exhibited a specific detection capability for CLZ. The fluorescence emission of the probe was enhanced in two concentration ranges: from 50 ng/mL to 1.0 μg/mL and from 1.0 to 15.0 μg/mL with a lower limit of quantification of 50 ng/mL, indicating the sensitivity of the probe for detecting CLZ plasma levels. The accuracy of the probe is favorable which could be recommended for CLZ monitoring in the biological media. Furthermore, this probe is highly specific towards CLZ in the presence of various interfering agents which is mainly caused by its ratiometric nature. The developed platform showed high reliability in quantifying CLZ concentrations in patients' plasma samples. Hence, the fabricated probe could be recommended as a reliable method for the routine detection of CLZ in clinical settings., (© 2024 John Wiley & Sons Ltd.)

Wound biofilms represent an elusive conundrum in contemporary treatment and diagnostic options, accredited to their escalating antibiotic resistance and interference in chronic wound healing processes. Here, we developed mesoporous polydopamine (mPDA) nanoparticles, and grafted with rhodamine B (Rb) as biofilm lipase responsive detection probe, followed by π - π stacking mediated ciprofloxacin (CIP) loading to create mP-Rb@CIP nanoparticles. mPDA NPs with a melanin structure could quench fluorescence emissions of Rb. Once encountering biofilm in vivo, the ester bond in Rb and mPDA is hydrolyzed by elevated lipase concentrations, triggering the liberation of Rb and restore fluorescence emissions to achieve real-time imaging of biofilm-infected wounds. Afterwards, the 808 nm near-infrared (NIR) illumination initiates a spatiotemporal controlled antibacterial photothermal therapy (PTT), boosting its effectiveness through photothermal-triggered CIP release for synergistic biofilm eradication. The mP-Rb@CIP platform exhibits dual diagnostic and therapeutic functions, efficaciously treating biofilm-infected wounds in vivo and in vitro. Particularly, the mP-Rb@CIP/NIR procedure expedites wound-healing by alleviating oxidative stress, modulating inflammatory mediators, boosting collagen synthesis, and promoting angiogenesis. Taken together, the theranostic nanosystem strategy holds significant potential for addressing wound biofilm-associated infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this work, two-dimensional (2D) Zn-HMT (Zn(NO 3 ) 2 (HMT) 2 (H 2 O) 2 ] n ) nanosheets were synthesized using a facile one-step chemical precipitation in the presence of Zn(NO 3 ) 2 , hexamine (HMT), and anhydrous ethanol at room temperature. Subsequently, hexagonal T x -ZnO (T x -ZnO refers to the zinc oxide (ZnO) nanoparticles) were synthesized by a high-temperature solid-phase method at different temperatures ( x = 500, 550, 600, 650, 700, 750, and 800 °C) nanoparticles with different morphologies were synthesized by a high-temperature calcination approach using 2D Zn-HMT nanosheets as precursor. The crystal structure, morphology, specific surface areas, surface and interface properties, optical properties, and charge migration behaviors of the as-synthesized T x -ZnO nanoparticles were characterized by powder X-ray diffraction (XRD), field-emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), high-resolution TEM (HRTEM), automatic specific surface and aperture analyzer, X-ray photoelectron spectroscopy (XPS), UV-visible spectrophotometer, photoluminescence (PL) spectra, and electrochemical impedance spectroscopy (EIS). The photocatalytic performances and stabilities of the as-synthesized typical T x -ZnO nanoparticles with various morphologies were evaluated and compared with the commercial ZnO (CM-ZnO) nanoparticle. The T700-ZnO nanoparticle with spherical and irregular morphology exhibited the highest photocatalytic activity (99.12%) for the degradation of Rhodamine B (RhB), compared to T500-ZnO (92.32%), T600-ZnO (90.65%), T800-ZnO (44.04%), and the CM-ZnO (88.38%) nanoparticle, which can be attributed to the cooperative effects of higher crystallinity, bigger crystal size, the strongest separation efficiency, the lowest recombination rate, the fastest charge carrier transfer path, and the highest charge-transfer efficiency. The superior photocatalytic activity illustrated by the T700-ZnO nanoparticle makes it have potential application prospects for the treatment of organic wastewater.

Green iron tea nanoparticles (GT-Fe NPs) were used as persulfate(PS) activators to oxidize rhodamine B (RhB) in this study. Optimized oxidative degradation condition was 0.033 mM Fe, 5 mM PS at pH 3.0 and 298 K with an initial RhB content of 50 mg/L. After 120 min of RhB degradation utilizing GT-Fe NPs activated PS, 99% of RhB reduction was achieved, while 98% RhB reduction with PS activated by citric acid-Fe 2+ (CA-Fe) with the same amount of Fe 2+ . This RhB reduction was due to the delayed release of Fe(II) in the GT-Fe NPs. The addition of GT-Fe NPs enhanced the synthesis of OH· and SO 4 - · while inhibiting the formation of O 2 - ·. A possible RhB degradation pathway was the chromophore destruction and ring-opening processes using GT-Fe NPs/PS, which produced a range of low molecular weight carboxylic acids (oxalic acid, lactic acid, acetic acid, and formic acid). GT-Fe NPs seem to be a promising persulfate activator in comparison to common activators such as CA-Fe.

In this work we presented novel strategy for increasing the performance of popular fluorescent probes on the basis of rhodamine-lactam platform. This strategy is based on the incorporation of probe molecules into the light-harvesting nanoparticles to pump modulated optical signal by Förster resonant energy transfer. Using the commercially available Cu 2+ probe as a reference chemical, we have developed an efficient approach to significantly improve its sensing performance. Within obtained nanoparticles coumarin-30 nanoantenna absorbs excitation light and pumps incorporated sensing molecules providing bright fluorescence to a small number of emitters, while changing the probe-analyte equilibrium from liquid-liquid to solid-liquid significantly increased the apparent association constant, which together provided a ∼100-fold decrease in the detection limit. The developed nanoprobe allows highly sensitive detection of Cu 2+ ions in aqueous media without organic co-solvents usually required for dissolution of the probe, and demonstrate compatibility with inexpensive fluorometers and the ability to detect low concentrations with the naked eye., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Mesoporous silica nanoparticles loaded with rhodamine B and capped with curcumin are used for the selective and sensitive fluorogenic detection of human serum albumin (HSA). The sensing mesoporous silica nanoparticles are loaded with rhodamine B, decorated with aminopropyl moieties and capped with curcumin. The nanoparticles selectively release the rhodamine B cargo in the presence of HSA. A limit of detection for HSA of 0.1 mg/mL in PBS (pH 7.4)-acetonitrile 95:5 v / v was found, and the sensing nanoparticles were used to detect HSA in spiked synthetic urine samples.

The incorporation between nano-polyvinyl alcohol (PVA) and nano-chitosan (Cs) to produce sandwich nanohybrid (SNH) for water treatment and improvement the adsorption of sofosbuvir drug (SOF). The photocatalytic activity and formation of reactive oxygen species (ROS) were detected with oxidation of organic dyes such as Rhodamine B (RhB), methylene blue (MB), and methyl orange (MO). The effect of SNH on the release of SOF in blood and inside the cells at pH 7.4 and pH 6.8, respectively were observed by UV-Visible spectroscopy (UV-Vis). The binding constant (K b ) was reported at 0.0035 min -1 and the loading constant at 0.0024 min -1 , while the release efficiency was 42.6% at pH 7.4 and 74.7% at pH 6.8. The efficiency of photocatalytic activity against organic dyes MO, MB, and RhB are detected at 2.4% and 1%, and 42%, respectively. The cytotoxicity of SNH has been observed with MDA-MB-231 and HepG2 cell line with three concentrations of SNH, where the little concentration has low effect on the HepG2 and high viability, this result was reversed with the high concentration, also the yellow color due to the lysis of the cells. The antioxidant of the SNH was detected by FRAP technique., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Polymer-lipid hybrid nanoparticles (PLHNPs) are novel nanoplatforms for the effective delivery of a lipophilic drug in the management of a variety of solid tumors. The present work was designed to develop exemestane (EXE) encapsulated D-alpha-tocopheryl polyethylene glycol succinate (TPGS) based PLHNPs (EXE-TPGS-PLHNPs) for controlled delivery of EXE for breast cancer management. EXE-TPGS-PLHNPs were formulated by single-step nano-precipitation technique and statistically optimized by a 3 3 Box-Behnken design using Design expert ® software. The polycaprolactone (PCL; X 1 ), phospholipon 90 G (PL-90G; X 2 ), and surfactant ( X 3 ) were selected as independent factors while particles size (PS; Y 1 ), polydispersity index (PDI; Y 2 ), and %entrapment efficiency (%EE; Y 3 ) were chosen as dependent factors. The average PS, PDI, and %EE of the optimized EXE-TPGS-PLHNPs was observed to be 136.37 ± 3.27 nm, 0.110 ± 0.013, and 88.56 ± 2.15% respectively. The physical state of entrapped EXE was further validated by Fourier-transform infrared spectroscopy, differential scanning calorimetry, and powder x-ray diffraction that revealed complete encapsulation of EXE in the hybrid matrix of PLHNPs with no sign of significant interaction between drug and excipients. In vitro release study in simulated gastrointestinal fluids revealed initial fast release for 2 h after that controlled release profile up to 24 h of study. Moreover, optimized EXE-TPGS-PLHNPs exhibited excellent stability in gastrointestinal fluids as well as colloidal stability in different storage concentrations. Furthermore, EXE-TPGS-PLHNPs exhibited distinctively higher cellular uptake and time and dose-dependent cytotoxicity against MCF-7 breast tumor cells compared to EXE-PLHNPs without TPGS and free EXE. The obtained results suggested that EXE-TPGS-PLHNPs can be a promising platform for the controlled delivery of EXE for the effective treatment of breast cancer., (© 2021 IOP Publishing Ltd.)

Ultrabright fluorescent nanoparticles (NPs) hold great promise for demanding bioimaging applications. Recently, extremely bright molecular crystals of cationic fluorophores were obtained by hierarchical coassembly with cyanostar anion-receptor complexes. These small-molecule ionic isolation lattices (SMILES) ensure spatial and electronic isolation to prohibit aggregation quenching of dyes. We report a simple, one-step supramolecular approach to formulate SMILES materials into NPs. Rhodamine-based SMILES NPs stabilized by glycol amphiphiles show high fluorescence quantum yield (30 %) and brightness per volume (5000 M -1  cm -1 /nm 3 ) with 400 dye molecules packed into 16-nm particles, corresponding to a particle absorption coefficient of 4×10 7  M -1  cm -1 . UV excitation of the cyanostar component leads to higher brightness (>6000 M -1  cm -1 / nm 3 ) by energy transfer to rhodamine emitters. Coated NPs stain cells and are thus promising for bioimaging., (© 2021 Wiley-VCH GmbH.)

Fluorescent probes are used in drug nanocarrier pre-clinical studies or as active compounds in theranostics and photodynamic therapy. In the biological medium, nanoparticles interact with proteins, which can result in the off-target release of their cargo. The present study used asymmetric flow field-flow fractionation with online multi-angle laser light scattering and fluorescence detection (AF4-MALLS-FLD) to study the release, transfer, and partition of fluorescent dyes from polymeric nanoparticles (NP). NP formulations containing the dyes Rose Bengal, Rhodamine B, DiI, 3-(α-azidoacetyl)coumarin and its polymer conjugate, Nile Red, and IR780 and its polymer conjugate were prepared. NP suspensions were incubated in a medium with serum proteins and then analyzed by AF4. AF4 allowed efficient separation of proteins (< 10 nm) from fluorescently labeled NP (range of 54 - 180 nm in diameters). The AF4 analyses showed that some dyes, such as Rose Bengal, IR780, and Coumarin were transferred to a high extent (68-77%) from NP to proteins. By contrast, for DiI and dye-polymer conjugates, transfer occured to a lower extent. The studies of dye release kinetics showed that the transfer of IR780 from NP to proteins occurs at a high extent (~50%) and rate, while Nile Red was slowly released from the NP over time with reduced association with proteins (~20%). This experiment assesses the stability of fluorescence labeling of nanocarriers and probes the transfer of fluorescent dyes from NP to proteins, which is otherwise not accessible with commonly used techniques of separation, such as dialysis and ultrafiltration/centrifugation employed in drug encapsulation and release studies of nanocarriers. Determining the interaction and transfer of dyes to proteins is of utmost importance in the pre-clinical evaluation of drug nanocarriers for improved correlation between in vitro and in vivo studies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: Accurate tumor identification and staging can be difficult. Aptamer-targeted indocyanine green (ICG)-nanoparticles can enhance near-infrared fluorescent imaging of pancreatic and prostate tumors and could improve early cancer detection. This project explored whether calcium-phosphosilicate nanoparticles, also known as NanoJackets (NJs), that were bioconjugated with a tumor-specific targeting DNA aptamer could improve the non-invasive detection of pancreatic and prostate tumors., Methods: Using in vivo near-infrared optical imaging and ex vivo fluorescence analysis, DNA aptamer-targeted ICG-loaded NJs were compared to untargeted NJs for detection of tumors., Results: Nanoparticles were bioconjugated with the DNA aptamer AP1153, which binds to the CCK-B receptor (CCKBR). Aptamer bioconjugated NJs were not significantly increased in size compared with unconjugated nanoparticles. AP1153-ICG-NJ accumulation in orthotopic pancreatic tumors peaked at 18 h post-injection and the ICG signal was cleared by 36 h with no evidence on uptake by non-tumor tissues. Ex vivo tumor imaging confirmed the aptamer-targeted NJs accumulated to higher levels than untargeted NJs, were not taken up by normal pancreas, exited from the tumor vasculature, and were well-dispersed throughout pancreatic and prostate tumors despite extensive fibrosis. Specificity for AP1153-NJ binding to the CCK-B receptor on pancreatic tumor cells was confirmed by pre-treating tumor-bearing mice with the CCK receptor antagonist proglumide. Proglumide pre-treatment reduced the in vivo tumoral accumulation of AP1153-NJs to levels comparable to that of untargeted NJs., Conclusion: Through specific interactions with CCK-B receptors, tumor-targeted nanoparticles containing either ICG or rhodamine WT were well distributed throughout the matrix of both pancreatic and prostate tumors. Tumor-targeted NJs carrying various imaging agents can enhance tumor detection., Competing Interests: Mr Christopher O McGovern reports a patent “DNA Aptamers Targeting the Cholecystokinin B Receptor (CCKBR) for Diagnosis and Treatment of Pancreatic Ductal Adenocarcinoma and other CCKBR-Expressing Lesions“ pending, a patent “Encapsulation and High Loading Efficiency of Phosphorylated Active Prodrug Metabolic Products in Nanoparticles“ pending. Dr Samuel S Linton reports a patent PCT/US2017/013769 pending. Dr James H Adair has patents 8,071,132 and 9,145,244 B2 issued to PendreaBio, Inc. JHA is also a cofounder and CSO of Keystone Nano for PendreaBio, Inc. Dr Gail L Matters reports a patent “Encapsulation and High Loading Efficiency of Phosphorylated Active Prodrug Metabolic Products in Nanoparticles“ pending and a patent “BIOCONJUGATION OF CALCIUMPHOSPHOSILICATE NANOPARTICLES FOR SELECTIVETARGETING OF CELLS IN VIVO” issued. The authors report no other conflicts of interest in this work., (© 2021 Abraham et al.)

The structural layers around oocytes make it difficult to deliver drugs aimed at treating infertility. In this study, we sought to identify nanoparticles (NPs) that could easily pass through zona pellucida (ZP), a special layer around oocytes, for use as a drug delivery carrier. Three types of NPs were tested: quantum dot NPs, PE-polyethylene glycol (PEG)-loaded poly(lactic- co -glycolic acid) (PLGA) NPs (PEG/PL), and tetramethylrhodamine-loaded PLGA NPs (TRNPs). When mouse oocytes were treated with NPs, only TRNPs could fully pass through the ZP and cell membrane. To assess the effects of TRNPs on fertility and potential nanotoxicity, we performed mRNA sequencing analysis to confirm their genetic safety. We established a system to successfully internalize TRNPs into oocytes. The genetic stability and normal development of TRNP-treated oocytes and embryos were confirmed. These results imply that TRNPs can be used as a drug delivery carrier applicable to germ cells.

Reversing the immunosuppressive tumor microenvironment (TME) is a strategic initiative to sensitize cancer immunotherapy. Emerging evidence shows that cyclic diguanylate monophosphate (c-di-GMP or cdG) can induce the stimulator of interferon genes (STING) pathway activation of antigen-presenting cells (APCs) and upregulate expression of type I interferons (IFNs) to enhance tumor immunogenicity. In vitro anionic cdG revealed fast plasma clearance, poor membrane permeability, and inadequate cytosolic bioavailability. Therefore, we explored a comprehensive " in situ vaccination" strategy on the basis of nanomedicine to trigger robust antitumor immunity. Rhodamine B isothiocyanate (RITC) fluorescent mesoporous silica nanoparticles (MSN) synthesized and modified with poly(ethylene glycol) (PEG) and an ammonium-based cationic molecule (TA) were loaded with negatively charged cdG via electrostatic interactions to form cdG@RMSN-PEG-TA. Treatment of RAW 264.7 cells with cdG@RMSN-PEG-TA markedly stimulated the secretion of IL-6, IL-1β, and IFN-β along with phospho-STING (Ser365) protein expression. In vivo cdG@RMSN-PEG-TA enhanced infiltration of leukocytes, including CD11c + dendritic cells, F4/80 + macrophages, CD4 + T cells, and CD8 + T cells within the tumor microenvironment (TME), resulting in dramatic tumor growth inhibition in 4T1 breast tumor-bearing Balb/c mice. Our findings suggest that a nanobased platform can overcome the obstacles bare cdG can face in the TME. Our approach of an in situ vaccination using a STING agonist provides an attractive immunotherapy-based strategy for treating breast cancer.

Insecticide resistance poses a significant threat to the control of arthropods that transmit disease agents. Nanoparticle carriers offer exciting opportunities to expand the armamentarium of insecticides available for public health and other pests. Most chemical insecticides are delivered by contact or feeding, and from there must penetrate various biological membranes to reach target organs and kill the pest organism. Nanoparticles have been shown to improve bioactive compound navigation of such barriers in vertebrates, but have not been well-explored in arthropods. In this study, we explored the potential of polyanhydride micro- and nanoparticles (250 nm- 3 μm), labeled with rhodamine B to associate with and/or transit across insect biological barriers, including the cuticle, epithelium, midgut and ovaries, in female Ae. aeygpti mosquitoes. Mosquitoes were exposed using conditions to mimic surface contact with a residual spray or paint, topical exposure to mimic contact with aerosolized insecticide, or per os in a sugar meal. In surface contact experiments, microparticles were sometimes observed in association with the exterior of the insect cuticle. Nanoparticles were more uniformly distributed across exterior tissues and present at higher concentrations. Furthermore, by surface contact, topical exposure, or per os, particles were detected in internal organs. In every experiment, amphiphilic polyanhydride nanoparticles associated with internal tissues to a higher degree than hydrophobic nanoparticles. In vitro, nanoparticles associated with Aedes aegypti Aag2 cells within two hours of exposure, and particles were evident in the cytoplasm. Further studies demonstrated that particle uptake is dependent on caveolae-mediated endocytosis. The propensity of these nanoparticles to cross biological barriers including the cuticle, to localize in target tissue sites of interest, and to reach the cytoplasm of cells, provides great promise for targeted delivery of insecticidal candidates that cannot otherwise reach these cellular and subcellular locations., Competing Interests: The authors have declared that no competing interests exist.

Developing novel drug carriers for pulmonary delivery is necessary to achieve higher efficacy and consistency for treating pulmonary diseases while limiting off-target side effects that occur from alternative routes of administration. Metal-organic frameworks (MOFs) have recently emerged as a class of materials with characteristics well-suited for pulmonary drug delivery, with chemical tunability, high surface area, and pore size, which will allow for efficient loading of therapeutic cargo and deep lung penetration. UiO-66, a zirconium and terephthalic acid-based MOF, has displayed notable chemical and physical stability and potential biocompatibility; however, its feasibility for use as a pulmonary drug delivery vehicle has yet to be examined. Here, we evaluate the use of UiO-66 nanoparticles (NPs) as novel pulmonary drug delivery vehicles and assess the role of missing linker defects in their utility for this application. We determined that missing linker defects result in differences in NP aerodynamics but have minimal effects on the loading of model and therapeutic cargo, cargo release, biocompatibility, or biodistribution. This is a critical result, as it indicates the robust consistency of UiO-66, a critical feature for pulmonary drug delivery, which is plagued by inconsistent dosage because of variable properties. Not only that, but UiO-66 NPs also demonstrate pH-dependent stability, with resistance to degradation in extracellular conditions and breakdown in intracellular environments. Furthermore, the carriers exhibit high biocompatibility and low cytotoxicity in vitro and are well-tolerated in in vivo murine evaluations of orotracheally administered NPs. Following pulmonary delivery, UiO-66 NPs remain localized to the lungs before clearance over the course of seven days. Our results demonstrate the feasibility of using UiO-66 NPs as a novel platform for pulmonary drug delivery through their tunable NP properties, which allow for controlled aerodynamics and internalization-dependent cargo release while displaying remarkable pulmonary biocompatibility.

This study is about fine tuning the targeting capacity of peptide-decorated nanoparticles to discriminate between cells that express different integrin make-ups. Using microfluidic-assisted nanoprecipitation, we have prepared poly(lactic acid-co-glycolic acid) (PLGA) nanoparticles with a PEGylated surface decorated with two different arginine-glycine-aspartic acid (RGD) peptides: one is cyclic (RGDFC) and has specific affinity towards α v β 3 integrin heterodimers; the other is linear (RGDSP) and is reported to bind equally α v β 3 and α 5 β 1 . We have then evaluated the nanoparticle internalization in two cell lines with a markedly different integrin fingerprint: ovarian carcinoma A2780 (almost no α v β 3 , moderate in α 5 β 1 ) and glioma U87MG (very high in α v β 3 , moderate/high in α 5 β 1 ). As expected, particles with cyclic RGD were heavily internalized by U87MG (proportional to the peptide content and abrogated by anti-α v β 3 ) but not by A2780 (same as PEGylated particles). The linear peptide, on the other hand, did not differentiate between the cell lines, and the uptake increase vs. control particles was never higher than 50%, indicating a possible low and unselective affinity for various integrins. The strong preference of U87MG for cyclic (vs. linear) peptide-decorated nanoparticles was shown in 2D culture and further demonstrated in spheroids. Our results demonstrate that targeting specific integrin make-ups is possible and may open the way to more precise treatment, but more efforts need to be devoted to a better understanding of the relation between RGD structure and their integrin-binding capacity.

Rhodamine derivatives have been widely investigated for their mitochondrial targeting and chemotherapeutic properties that result from their lipophilic cationic structures. In previous research, we have found that conversion of Rhodamine 6G into nanoGUMBOS, i.e., nanomaterials derived from a group of uniform materials based on organic salts (GUMBOS), led to selective chemotherapeutic toxicity for cancer cells over normal cells. Herein, we investigate the chemotherapeutic activity of GUMBOS derived from four different rhodamine derivatives, two bearing an ester group, i.e., Rhodamine 123 (R123) and SNAFR-5, and two bearing a carboxylic acid group, i.e., rhodamine 110 (R110) and rhodamine B (RB). In this study, we evaluate (1) relative hydrophobicity via octanol-water partition coefficients, (2) cytotoxicity, and (3) cellular uptake in order to evaluate possible structure-activity relationships between these different compounds. Intriguingly, we found that while GUMBOS derived from R123 and SNAFR-5 formed nanoGUMBOS in aqueous medium, no distinct nanoparticles are observed for RB and R110 GUMBOS. Further investigation revealed that the relatively high water solubility of R110 and RB GUMBOS hinders nanoparticle formation. Subsequently, while R123 and SNAFR-5 displayed selective chemotherapeutic toxicity similar to that of previously investigated R6G nanoGUMBOS, the R110 and RB GUMBOS were lacking in this property. Additionally, the chemotherapeutic toxicities of R123 and SNAFR-5 nanoGUMBOS were also significantly greater than R110 and RB GUMBOS. Observed results were consistent with decreased cellular uptake of R110 and RB as compared to R123 and SNAFR-5 compounds. Moreover, these results are also consistent with previous observations that suggest that nanoparticle formation is critical to the observed selective chemotherapeutic properties as well as the chemotherapeutic efficacy of rhodamine nanoGUMBOS.

Nanoparticle-cell-nanoparticle communication by stigmergy was demonstrated using two capped nanodevices. The first community of nanoparticles (i.e.S(RA)IFN) is loaded with 9-cis-retinoic acid and capped with interferon-γ, whereas the second community of nanoparticles (i.e.S(sulf)PIC) is loaded with sulforhodamine B and capped with poly(I:C). The uptake of S(RA)IFN by SK-BR-3 breast cancer cells enhanced the expression of TLR3 receptor facilitating the subsequent uptake of S(sulf)PIC and cell killing.

Osteoarthritis, which is characterized by irreversible destruction of articular cartilage and severe inflammation of joint capsule, may be effectively treated via the synergistic therapy of lubrication restoration and local drug intervention. In this study, zwitterionic polymer-grafted mesoporous silica nanoparticles (MSNs@pSBMA) with the property of enhanced lubrication and sustained drug release were successfully synthesized via photopolymerization of 3-[dimethyl-[2-(2-methylprop-2-enoyloxy) ethyl] azaniumyl] propane-1-sulfonate polymer (pSBMA) on the surface of MSNs. The tribiological test showed that the lubrication performance of MSNs@pSBMA was remarkably improved, with a reduction of 80% in friction coefficient compared with MSNs. It was attributed to hydration lubrication mechanism by which a tenacious hydration layer was formed surrounding the N + (CH 2 ) 2 (CH 3 ) 2 and SO 3 headgroups in the pSBMA polyelectrolyte polymer. Additionally, the surface morphology analysis of the tribopairs demonstrated that MSNs@pSBMA were endowed with excellent anti-wear performance. Importantly, the drug release test illustrated that, compared with MSNs, MSNs@pSBMA achieved good sustained drug release behavior. In summary, the MSNs@pSBMA nanoparticles developed herein, as an injectable lubricant with enhanced lubrication and drug delivery, may represent a promising approach for the treatment of osteoarthritis.- headgroups in the pSBMA polyelectrolyte polymer. Additionally, the surface morphology analysis of the tribopairs demonstrated that MSNs@pSBMA were endowed with excellent anti-wear performance. Importantly, the drug release test illustrated that, compared with MSNs, MSNs@pSBMA achieved good sustained drug release behavior. In summary, the MSNs@pSBMA nanoparticles developed herein, as an injectable lubricant with enhanced lubrication and drug delivery, may represent a promising approach for the treatment of osteoarthritis., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Colloidal systems prepared from carbohydrates are subject of intense research due to their potential to enhance drug permeability through biological membranes, however their characteristics and performance are never compared directly. Here we report the results of a comparative investigation of a series of butylglyceryl-modified polysaccharides (chitosan, guar gum, and pullulan) that were formulated into nanoparticles and loaded with a range of model actives (Doxorubicin, Rhodamine B, Angiotensin II). Butylglyceryl-modified guar gum and corresponding pullulan nanocarriers were more stable at physiological pH compared to those obtained from modified chitosan, and studies of the in-vitro interactions with mouse brain endothelial cells (bEnd3) indicated an increased biological membrane permeability and lack of toxicity at application-relevant concentrations. No significant haemolytic effect was observed, and confocal microscopy and flow cytometry studies confirmed the efficient cellular uptake and cytoplasmic localisation of NPs. Most promising characteristics for brain drug delivery applications were demonstrated by butylglyceryl pullulan nanocarriers., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The emergence of viral nanotechnology over the preceding two decades has created a number of intellectually captivating possible translational applications; however, the in vitro fate of the viral nanoparticles in cells remains an open question. Herein, we investigate the stability and lifetime of virus-like particle (VLP) Qβ-a representative and popular VLP for several applications-following cellular uptake. By exploiting the available functional handles on the viral surface, we have orthogonally installed the known FRET pair, FITC and Rhodamine B, to gain insight of the particle's behavior in vitro. Based on these data, we believe VLPs undergo aggregation in addition to the anticipated proteolysis within a few hours of cellular uptake.

Fluorescent submicron particles of fluorinated methacrylate (HFMBA) with long-term stability have been synthesized and characterized with regard to their potential applications. Rhodamine B (RBITC) isothiocyanate was used as the fluorescent component. The core-shell structure of the particles effectively protected the dye against bleaching. HFBMA nanoparticle (NP) stability was confirmed after seven years of storage. Only slight differences were found in the polydispersity index (pdi) from 0.002 to 0.010. Particle size measurements were carried out using dynamic light scattering (DLS), nanoparticle tracking (NTA), and fluorescence correlation spectroscopy (FCS). The hydrodynamic diameter evaluated by different methods were in good agreement, respectively: 184-550 nm, 218-579 nm, and 236-508 nm. Particle and core morphology was estimated by using scanning and transmission electron microscopy (SEM and TEM). The ability to recognize particles in 3D as a reference sample in biological media has been confirmed by epifluorescence optical microscopy, confocal laser scanning microscopy, and super-resolution confocal microscopy (STED).

Combinatorial techniques can accelerate the discovery and development of polymeric nanodelivery devices by pairing high-throughput synthesis with rapid materials characterization. Biodegradable polyanhydrides demonstrate tunable release, high cellular internalization, and dose sparing properties when used as nanodelivery devices. This nanoparticle platform shows promising potential for small molecule drug delivery, but the pace of understanding and rational design of these nanomedicines is limited by the low throughput of conventional characterization. This study reports the use of a high-throughput method to synthesize libraries of a newly synthesized, rapidly eroding polyanhydride copolymer based on 1,8-bis( p -carboxyphenoxy)-3,6-dioxaoctane (CPTEG) and sebacic acid (SA) monomers. The high-throughput method enabled efficient screening of copolymer microstructure, revealing weak block-type and alternating architectures. The high-throughput method was adapted to synthesize nanoparticle libraries encapsulating hydrophobic model drugs. Drug release from these nanoparticles was rapid, with a majority of the payload released within 3 days. Drug release was dramatically slowed at acidic pH, which could be useful for oral drug delivery. Rhodamine B (RhoB) release kinetics generally followed patterns of polymer erosion kinetics, while Coomassie brilliant blue (CBB) released the fastest from the slowest degrading polymer chemistry and vice versa. These differences in trends between copolymer chemistry and release kinetics were hypothesized to arise from differences in mixing thermodynamics. A high-throughput method was developed to synthesize polymer-drug film libraries and characterize mixing thermodynamics by melting point depression. Rhodamine B had a negative χ for all copolymers with <30 mol % CPTEG tested, indicating a tendency toward miscibility. By contrast, CBB χ increased, eventually becoming positive near 15:85 CPTEG:SA, with increasing CPTEG content. This indicates an increasing tendency toward phase separation in CPTEG-rich copolymers. These in vitro results screening polymer-drug interactions showed good agreement with in silico predictions from Hansen solubility parameter estimation and were able to explain the observed differences in model drug release trends.

Encapsulating drugs in functional nanoparticles provides controlled and targeted release of drugs. In this study, a general approach for encapsulating hydrophobic drugs in polyelectrolyte nanoparticles was developed for a controlled drug release. Gemcitabine (GEM), an anticancer drug for pancreatic ductal adenocarcinoma (PDAC), was used as a model drug to produce poly(acrylic acid) (PAA)-GEM conjugate nanoparticles to achieve a controlled release of GEM in cells. The PAA-GEM conjugate nanoparticles were fabricated by coupling GEM onto PAA through the formation of amide bonds. The hydrophobic interactions of GEM molecules induced the formation of the nanoparticles with the GEM core and PAA shell. Fabrication conditions such as the PAA/GEM ratio and pH were optimized to achieve high structure stability and drug loading efficiency. The size and surface charge of the nanoparticles were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and zeta potential measurement. The optimized PAA-GEM nanoparticles had a size around 12 nm, 30 nm and 60 nm in dry state, water, and phosphate buffered saline (PBS), respectively. The encapsulation efficiency was 29.29 ± 1.7%, and the loading capacity was 9.44 ± 0.46%. Less than 7% GEM was released from the PAA-GEM nanoparticles after 96 hour incubation in phosphate buffered saline. The cytotoxic efficacy of the PAA-GEM nanoparticles in cancer cells was investigated through viability studies of PANC-1, a human pancreatic cancer cell line. It was found that the PAA-GEM nanoparticles had more than a 48 hour delay of releasing GEM and had the same cytotoxic efficacy in PANC-1 cells as free GEM. The uptake of the PAA-GEM nanoparticles by PANC-1 cells was investigated using PAA-GEM labeled by rhodamine G6. Fluorescence and bright field overlay images indicated that the PAA-GEM nanoparticles were taken up by PANC-1 cells within 2 hours. It is believed that the PAA-GEM nanoparticles were decomposed in PANC-1 cells and GEM was released from the nanoparticles.

We report the postsynthetic functionalization of Prussian blue (PB) nanoparticles by two different luminophores (2-aminoanthracene and rhodamine B). We show that the photoluminescence properties of the fluorophores are modified by a confinement effect upon adsorption and demonstrate that such multifunctional nanosized systems could be used for in vitro imaging.

The present study focused on the development and optimization of glycerosomes for dermal delivery of fisetin. The fisetin loaded glycerosomes formulation was optimized by Box-Behnken design. The independent variables were the lipoid S 100, glycerol, and sonication time, whereas the dependent variables were the vesicles size, entrapment efficiency, and flux. The mechanism of skin penetration of fisetin loaded glycerosomes formulation was determined by the DSC and FTIR studies. Confocal scanning microscopy was used to detect the penetration ability of glycerosomes. The optimized fisetin loaded glycerosomes formulation was converted into a Carbopol® gel matrix, and the latter was analyzed for various parameters. The optimized formulation of glycerosomes presented vesicles size, entrapment efficiency and flux of 138.8 ± 4.09 nm, 86.41 ± 2.95% and 5.04 ± 0.17 µg/cm 2 /h, respectively. The transmission electron microscopy of optimized fisetin loaded formulation revealed the spherical and sealed structure of glycerosomes vesicles. The confocal study confirmed that the Rhodamine B incorporated glycerosomes penetrated up to deeper layers of skin. The DSC and FTIR studies revealed that the hydration of skin layers and skin lipid fluidization could be the penetration mechanism of fisetin glycerosomes formulation. The optimized fisetin loaded glycerosomes gel formulation presented a flux of 4.24 ± 0.14 μg/cm 2 /h, and exhibited zero-order release kinetics. The texture analysis of fisetin glycerosomes gel displayed a sufficient hardness, consistency, cohesiveness, and index of viscosity. It was concluded that the prepared fisetin loaded glycerosomes gel was suitable for the dermal application., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A novel nanoarchitecture (MSN-Tb-UbR) was prepared by modifying rhodamine B-labelled Ubs (Ub-Rs) on the surface of mesoporous silica nanoparticles (MSNs) loaded with Tb 3+ -complexes. The MSN-Tb-UbR exhibits ratiometric sensing ability for DUB (UCH-L1) with good sensitivity and selectivity.

Purpose: Solid lipid nanoparticles are largely used in biomedical research and are characterized by high stability and biocompatibility and are also able to improve the stability of various loaded molecules. In vitro studies demonstrated that these nanoparticles are low cytotoxic, while in vivo studies proved their efficiency as nanocarriers for molecules characterized by a low bioavailability. However, to our knowledge, no data on the systemic biodistribution and organ accumulation of solid lipid nanoparticles in itself are presently available., Methods: In this view, we investigated the solid lipid nanoparticles biodistribution by a multimodal imaging approach correlating in vivo and ex vivo analyses. We loaded solid lipid nanoparticles with two different fluorophores (cardiogreen and rhodamine) to observe them with an optical imager in the whole organism and in the excised organs, and with fluorescence microscopy in tissue sections. Light and transmission electron microscopy analyses were also performed to evaluate possible structural modification or damage due to nanoparticle administration., Results: Solid lipid nanoparticles loaded with the two fluorochromes showed good optic characteristics and stable polydispersity. After in vivo administration, they were clearly detectable in the organism. Four  hours after the injection, the fluorescent signal occurred in anatomical districts corresponding to the liver and this was confirmed by the ex vivo acquisitions of excised organs. Brightfield, fluorescence and transmission electron microscopy confirmed solid lipid nanoparticles accumulation in hepatocytes without structural damage., Conclusion: Our results support the systemic biocompatibility of solid lipid nanoparticles and demonstrate their detailed biodistribution from the whole organism to organs until the cells., Competing Interests: The authors declare that they have no competing interests., (© 2020 Mannucci et al.)

pH regulates the function of many organelles and plays a pivotal role in requiring multitud cellular behaviors. Compared with single fluorescent probes, ratio fluorescent probes have higher sensitivity and immunity to interference. Herein, a novel Janus ratio nanoprobe was developed for intracellular pH detection. Modified rhodamine B probe and fluorescein isothiocyanate (FITC) were individually encapsulated in the independent hemispheres of Janus microparticles fabricated via Pickering emulsion. Moreover, it exhibits a satasified ratiometric detection of pH compared to the previous core-shell structure and organic small molecule probe. Accordingly, the Janus nanoprobe possesses many important features as an attractive sensor, including high anti-jamming capability, excellent stability, good reversibility and low cytotoxicity. Variations of the two fluorescence intensities (Fgreen/Fred) resulted in a ratiometric pH fluorescent sensor, which can respond to wide range of pH values from 3 to 8. To be more specific, with a single excitation wavelength of 488 nm, there are dual emission bands centered at 538 nm and 590 nm. Also the Janus nanoprobe displays a excellent linear relationship in the physiologically relevant pH range of 4.0-6.0. Consequently, detecting of pH and imaging was successfully achieved in living cells, which provides a simple and reliable method for detecting intracelluar pH and other similar substances., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Photothermal therapy following microscopic temperature detection can avoid overheating effects or insufficient heating, and thus improve therapeutic efficacy. In this study, biocompatible dual-functional nanoparticles (NPs) are constructed from polypyrrole (PPy) and rhodamine B (RB) by a one-step modified polymerization method. The polypyrrole serves as a photothemal agent, and rhodamine B acts as a temperature-sensing probe. The polypyrrole-rhodamine B (PPy-RB) NPs possess a high photothermal effect on irradiation by 808 nm laser, and a competent temperature sensitivity for the real-time temperature monitoring based on the emission intensity response of rhodamine B. After acting on HepG2 cells, the PPy-RB NPs can effectively induce cancer cell death, and the microscopic temperature is monitored by fluorescence feedback from rhodamine B during PTT by laser confocal microscopy. Hence, the proposed approach can supply a facile and promising way for the fabrication of effective theranostic nanoplatforms assisted by self-monitoring of cancer therapeutic processes.

Multicompartmentalized nanostructures are of interest because they can provide unique physicochemical properties and multifunctionalities in each compartment. Furthermore, stimuli-responsive anisotropic nanostructures (ANPs) with distinct opposite charges would be useful for drug delivery systems because different drug release kinetics could be achieved from each compartment in response to both charge and stimuli. In this study, stimuli-responsive ANPs were formed via electrohydrodynamic cojetting of poly( N -isopropylacrylamide)-based copolymers with opposite charges. The positively charged compartment consisted of poly( N -isopropylacylamide- co -stearyl acrylate- co -allylamine) (poly(NIPAM- co -SA- co -AAm)) (i.e., PNSAAm) and poly( N -isopropylacylamide- co -stearyl acrylate- co -acrylic acid) (poly(NIPAM- co -SA- co -AAc)) (i.e., PNSAAc). The two distinct compartments of ANPs were physically cross-linked through hydrophobic interactions within the copolymers. Oppositely charged, small-molecule model drugs (fluorescein sodium salt and rhodamine 6G) were separately encapsulated within each compartment and released based on changes in noncovalent interactions and temperature. Furthermore, two different biomacromolecule drugs with opposite charges, bovine serum albumin and lysozyme (which were complexed with polysaccharides by hydrophobic ion pairing), were loaded within the ANPs. Electrostatic interactions between the encapsulated drugs and each ANP compartment controlled the rate of drug release from the ANPs. In addition, these ANPs showed a thermally induced actuation, leading to drug release at different rates due to the collapse of poly(NIPAM)-based copolymers under aqueous conditions. This work may be useful for decoupled drug release kinetics.

Although post-synthetic modification (PSM) has been successfully applied to NMOF decoration, only a handful of PSM-based single-crystal-to-single-crystal (SCSC) examples have been reported, particularly those involving multistep MOF-based SCSC transformations. In this contribution, three new MOFs, namely, UiO-68-NCS, UiO-68-R6G and UiO-68-R6G', were prepared via the single-crystal-to-single-crystal post-synthetic modification approach. For bioimaging, nanosized UiO-68-NCS, UiO-68-R6G, and UiO-68-R6G' were also prepared. Herein, nanosized UiO-68-R6G with a rhodamine-based fluorescence switch was found to be a highly sensitive and selective fluorescent probe for the detection of Hg2+ both in vitro and in vivo.

Supercritical Emulsion Extraction (SEE) and Supercritical assisted Liposome formation (SuperLip), use dense gases such as carbon dioxide (dCO 2 ) to fabricate advanced micro/nanocarriers. SEE uses dCO 2 to extract solvent from the oily phase of an emulsion and obtain biopolymer microbead; For this study, poly-Lactic Acid (PLA) microbeads of 1 ± 0.2 μm in mean size loaded at 1 µg/mg PLA with Rhodamine B (ROD) were prepared by SEE; the beads showed a solvent residue lower than 10 ppm and encapsulated the fluorochrome with an efficiency of 90%. SuperLip uses dCO2 to enhance lipid/ethanol/water mixing and to promote the ethanol extraction from liposome suspension. In this case, phosphatidyl-choline (PC) vesicles with a mean size of 0.2 ± 0.05 μm and loaded with Fluorescein Iso-ThioCyanate (FITC) at 8 µg/mg PC were prepared; small unilamellar structure was observed for all the vesicles with FITC encapsulation efficiency of 80%. Ethanol residue of 50 ppm was measured in all the liposome suspensions. The bioavailability of microbeads and nanoliposomes was assessed through incubation with human monocytes previously isolated from healthy donors' blood. A specifically optimized protocol that allowed their quenching on the cell surface was developed to monitor by flow cytometer assay only the cell population that effectively internalized the carriers. When microbeads were tested, the percentage of alive internalizing monocytes was of about 30%. An internalization of 96.1 ± 21% was, instead, obtained at dosage of 0.1 mg/mL for nanoliposomes. In this last case, monocytes showed a vitality of almost 100% after vesicles internalization at all the concentrations studied; on the other hand, cell apoptosis progressively increased in a dose/response manner, after polymer microbeads phagocytosis. The proposed data suggested that dCO 2 technologies can be reliably used to fabricate intracellular carriers., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Synthesis and application of three-dimensional TiO 2 hierarchical architectures are one of the major priorities in the research and development of TiO 2 catalysts. Using bacteria as a template and a reactor, a bioinspired strategy was developed in the present study to synthesize nanosheet-assembled TiO 2 hierarchical architectures (N-TiO 2 -HA) and relative composites for photocatalytic and electrocatalytic applications. In the first part of this work, three kinds of bacteria were used for the synthesis of N-TiO 2 -HA with satisfactory monodispersity, and the growth mechanism was investigated. In the second part, porous TiO 2 hollow spheres (P-TiO 2 -HS), which were obtained by calcining N-TiO 2 -HA at 750 °C in air, were incorporated with MIL-101(Fe) to improve the visible-light photocatalytic efficiency. The results of the photo-Fenton-assisted degradation of rhodamine B and ciprofloxacin indicate that the synthesized composites have excellent visible-light photocatalytic activity. In the third part, the nanosheet-assembled TiO 2 -carbon hollow spheres (N-TiO 2 -C-HS), which were obtained by calcining N-TiO 2 -HA at 750 °C in argon atmosphere, were electrodeposited with Pt for electrocatalytic oxidation of methanol. The electrochemical measurements show that Pt-deposited N-TiO 2 -C-HS have better electrocatalytic activity, stability, and tolerance to CO poisoning than commercial Pt/C catalysts.

Semiconductors are promising photocatalysts for the use of sunlight in energy conversion and environmental remediation. To this end, various synthetic pathways have been proposed to increase their photocatalytic efficiency, catalytic stability, recycle, and reuse. In this work, mixed phase CdS nanoparticles were loaded on the surface of activated biomass carbons to prepare composite photocatalysts via hydrothermal syntheses, which were further applied to photocatalytic degradation of rhodamine B (RhB) under visible irradiation. The composite photocatalysts displayed considerable specific surface area (up to 672 m 2 g -1 ) and suitable band gap energy of ca. 2.1 eV. Due to the excellent light adsorption ability and chemical stability, these composite photocatalysts exhibited excellent photocatalytic capacity toward RhB degradation under visible irradiation. Moreover, the photocatalytic stability was also demonstrated by cyclic experiments, by which the composite photocatalysts retained over 80% of the initial catalytic activity after 4 consecutive runs.

Development of luminescent probes for rapid and effective discrimination and detection of cancer cells has the potential to address the current challenges in early diagnosis and treatment monitoring of cancer diseases. In this work, we report the preparation of a unique folic acid (FA)-functionalized dual-emissive nanoprobe, CTMR@BHHBCB-Eu-FA, for steady-state and time-gated luminescence "double-check" imaging of cancer cells. The nanoprobe was engineered by covalently doping two luminescent dyes, 5-carboxytetramethylrhodamine (CTMR) and BHHBCB-Eu 3+ , in core and shell of silica nanoparticles, followed by surface modification of the nanoparticles with FA, a cancer cell-targeting molecule. As-prepared nanoprobe is monodisperse and highly stable in buffer displaying two strong emissions, short-lived emission from CTMR at 584 nm and long-lived emission from BHHBCB-Eu 3+ at 612 nm. The nanoprobe is biocompatible, and can specifically recognize folate receptor (FR)-overexpressed cancer cells through the FA-FR binding interaction. Using the nanoprobe, the "double-check" imaging of HeLa cells was successfully achieved at steady-state and time-gated luminescence modes, indicating the capability of the nanoprobe for cancer cell imaging., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Nanoparticles, such as TiO 2 particles, have a great potential for biomedical applications due to their ultra-small size and large specific surface area. However, their detection within cells is to date more than challenging. Thus, implementing fluorescence properties to nanoparticles via their controlled functionalisation with an organic chromophore is an original and efficient strategy to enable their visualization. In this work, a silylated coupling agent bearing a luminescent rhodamine B group was synthesised and grafted on the surface of anatase nanoparticles. The successful functionalisation was demonstrated via zeta potential, dynamic light scattering and diffuse reflectance infrared Fourier transform analyses. Remarkably, the obtained luminescent TiO 2 particles showed an improved photocatalytic activity compared to the pristine nanoparticles. Both, as-synthesised and functionalised TiO 2 nanoparticles samples appear to be non-toxic towards malignant and non-malignant cells. Moreover, the detection of the functionalised particles within cultured cells was proven to be easy and efficient via confocal fluorescence microscopy., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Liposomes are nanocarriers composed of phospholipids, especially designed to potentially carry drugs. However, liposomes suffer in terms of leakage of small hydrophilic drugs. To control the release, a system with lipid shell and polymeric viscous core, namely Hybrid liposome/polymer inside (HLP in ), has been designed. For this purpose, we setup a syringe pump apparatus equipped with homemade tubing system. HLPin formulation consisting of poloxamer (5% w/v) was found to be optimal when produced at injection rates of 5 mL.min -1 . Then, we tend to characterize the HLP in with DLS, TEM, TRPS, thermal analysis and densitometry in comparison with a polymer added after formation of the liposomes. The optimal formulation was evaluated for its stability and cytotoxicity. The selected conditions and composition resulted in nanocarriers which are highly reproducible with mono-disperse size distribution with an average size of 206 ± 4.8 nm and a polydispersity index of 0.15 ± 0.015. Densitometry and thermal analysis results confirmed the formation of HLP in . Interestingly, HLP in were stable over 2 months, produced no cytotoxicity and exhibited slow release of rhodamine and Doxorubicin in comparison to liposome formulation. Our homemade tubing system coupled with syringe pump apparatus achieved reproducible, precisely controlled production for the HLPin formulation which can be scale up., (Copyright © 2019. Published by Elsevier B.V.)

Here, we have developed a new colorimetric and luminescence nanosensor, based on upconversion nanoparticles (UCNPs), for in vitro and ex vivo measurement of carbon monoxide (CO). The nanoprobe has two strong fluorescence emission peaks in the UCNP core to excite fluorophores at 540 and 800 nm. The CO-responsive palladium ion-bounded rhodamine B derivatives (Pd-RBDs) are encapsulated in the mesoporous silica (mSiO 2 ) shell and the particles outside the cyclodextrin (CD) layer. Reduction of palladium ions by CO results in the release of palladium from the Pd-RBDs, thereby inducing the closure of the spiro ring of the RBD and the accompanying reduction of rhodamine B (RB) absorption at 500-600 nm overlapping with the luminescence spectrum of UCNPs maximized at 540 nm. Therefore, the I 540 / I 800 ratio of the nanoprobe will increase when CO is present, making it possible to quantitatively measure CO. Besides working in a clean buffer environment with known [CO], this method was evaluated using living cells and tissue sections. Additionally, these probes were also successfully used to investigate the CO-related protective activity of anti-hepatic ischemia-reperfusion injury (HIRI) oligopeptides.

Chitosan has received a lot of attention as a carrier for small interfering RNA (siRNA), due to its capacity for complexation and intracellular release of these molecules. However, one of its limitations is its insolubility at neutral pH and the tendency towards aggregation of its nanoparticles in isotonic ionic strength. In this study, a series of amphipathic chitosans were synthesized by varying the degree of acetylation (DA) from ˜2 to ˜30 mol% and the degree of substitution (DS) from 5 to 25%. by tertiary amino groups (DEAE) The results showed that the adjustment of these parameters decreases the interparticle interactions mediated by hydrogen bonding to obtain nanoparticles with improved colloidal stability. siRNA-containing nanoparticles of 100 to 150 nm with low polydispersities (0.15-0.2) and slightly positive zeta potentials (˜+ 5 mV) were resistant to aggregation at pH 7.4 and ionic strength of 150 mM. This resistance to aggregation is provided by changes on the nanoparticle surface and highlights the importance of more organized self-assembly in providing colloidal stability at physiological conditions. Additionally, the PEGylation of the most promising vectors conferred favorable physicochemical properties to nanoparticles. The chitosans and their nanoparticles exhibited low toxicity and an efficient cell uptake, as probed by confocal microscopy of rhodamine labeled vectors. The results provide a new approach to overcome the limited stability of chitosan nanoparticles at physiological conditions and show the potential of these amphipathic chitosans as siRNA carriers., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

A controllable drug delivery system demonstrates a promising tool for diverse biomedical applications. In this work, a group of amphiphilic macromolecules was designed and prepared via Schiff base reactions between 2,3-dialdehyde cellulose (DAC) with oleylamine and amino-containing compounds. Benefiting from the self-assemble process of these amphiphilic macromolecules in the poor solvent, a group of novel pH-responsive nanoparticles (NPs) were facilely fabricated by using nanoprecipitation dropping technique. The high amount of aldehyde groups on DAC chains enabled immobilization of tunable amounts of amine compounds (up to 1.67 mmol/g) in the NPs. Furthermore, the Schiff base bonds in NPs allowed the efficient release of the drug in acidic tumor microenvironment by cleaving the Schiff base linkages. This study demonstrates the formation of a group of novel pH-sensitive and drug-loadable NPs, which provide a simple and efficient drug delivery system for the potential application for cancer treatment., (Copyright © 2019. Published by Elsevier Ltd.)

Autophagy is associated with the proliferation and differentiation of mesenchymal stem cells (MSCs). In this study, we investigated the biological impact of silica-based nanobiomateiral-induced autophagy on the differentiation of MSCs, in which the nanoparticulate cues include solid silica nanoparticles (SSN), mesoporous silica nanoparticles (MSN) and biodegradable mesoporous silica nanoparticles (DMSN). The treatment with SSN significantly up-regulated the LC3-II expression via ERK1/2 and AKT/mTOR signaling pathways compared to DMSN and MSN, leading to a higher autophagic activity in MSCs. The enhanced protein adsorption of DMSN and MSN could prevent the direct interaction between cells and nanoparticles, which consequently reduces the autophagic stimulation of MSCs. It should be noted that MSCs exhibited increased differentiation potential when the autophagic activity was enhanced by the treatment with different nanoparticles. In comparison, no difference in the cell differentiation potential was found when an autophagy inhibitor (chloroquine, CQ) was incorporated in all groups. The study may contribute to the development of silica-based nanobiomaterials in the future.

Polymeric nanoparticles as drug delivery systems have the potential to improve the therapeutic efficacy and reduce the toxicity of chemotherapeutic drugs by enhancing the drug selectivity in vivo. The efficacy is directly dependent on the polymeric nanoparticles' in vivo fate. Therefore, it is very important to develop a method to stably label the polymeric nanoparticles for detecting the in vivo fate. Here, we report a method to stably label self-assembled nanoparticles by the incorporation of rhodamine B-conjugated poly(ε-caprolactone) (PCL-RhoB). Only 1% of PCL-RhoB was released from the RhoB-labeled polymeric nanoparticles (RhoB-PNPs) in phosphate buffer within 12 hours, which suggested that the signal of PCL-RhoB can be used to represent the behaviors of polymeric nanoparticles both in vitro and in vivo. PCL-RhoB could be effectively extracted and quantitatively detected by ultra-high-performance liquid chromatography (UPLC) in various media, such as PBS, a cell culture medium containing 10% FBS (pH = 7.4 and pH = 6.8), mouse serum, simulated intestinal fluid and cell or tissue lysis. The intracellular contents of PCL-RhoB in MDA-MB-231 cells detected by UPLC were linearly correlated to the concentration of the RhoB-PNPs. In addition, the contents of PCL-RhoB in plasma and the spleen were proportional to the injected dose of RhoB-PNPs in vivo. As an application example, the pharmacokinetics and biodistribution of the nanoparticles over time in vivo were analyzed following intravenous injection to confirm the feasibility of this method.

Targeted tumor imaging and efficient specific gene delivery in vivo has been one of the main challenges in gene-based cancer diagnosis and therapy. Herein, we engineered a citric acid-based polymer with intrinsical photoluminescence and gene loading capacity to achieve targeted delivery of siRNA and tumor imaging in vitro and in vivo. The multifunctional platform was formed from the self-assembling of poly (citric acid)-polymine conjugated with folic acid and rhodamine B (PPFR). PPFR showed stable photoluminescent ability and could effectively bind and protect the siRNA against RNase degradation. PPFR also exhibited good blood compatibility and cell compatibility against C2C12, MCF-7 and A549. Compared with commercial transfection agent Lipofectamine™ 2000, PPFR had a high cellular uptake, equivalent transfection efficiency and effectively down-regulated intracellular p65 expression in A549 cancer cells. Importantly, PPFR could efficiently accumulate and label the tumor tissue through the fluorescent imaging, selectively deliver siRNA into tumor tissue in vivo based on the tumor-bearing nude mice model. This work may provide a facile strategy to synthesize multifunctional biocompatible biomaterials for targeted tumor imaging and gene therapy., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Despite advances in cancer therapies, glioblastoma multiforme treatment remains inefficient due to the brain-blood barrier (BBB) inhibitory activity and to the low temozolomide (TMZ) chemotherapeutic selectivity. To improve therapeutic outcomes, in this work we propose two strategies, (i) photodynamic therapy (PDT) as adjuvant treatment and (ii) engineering of multifunctional theranostic/targeted nanoparticles ( m-NPs) that integrate biotin as a targeting moiety with rhodamine-B as a theranostic agent in pluronic P85/F127 copolymers. These smart m-NPs can surmount the BBB and coencapsulate multiple cargoes under optimized conditions. Overall, the present study conducts a rational m-NP design, characterization, and optimizes the formulation conditions. Confocal microscopy studies on T98-G, U87-MG, and U343 glioblastoma cells and on NIH-3T3 normal fibroblast cells show that the m-NPs and the encapsulated drugs are selectively taken up by tumor cells presenting a broad intracellular distribution. The formulations display no toxicity in the absence of light and are not toxic to healthy cells, but they exert a robust synergic action in cancer cells in the case of concomitant PDT/TMZ treatment, especially at low TMZ concentrations and higher light doses, as demonstrated by nonlinear dose-effect curves based on the Chou-Talalay method. The results evidenced different mechanisms of action related to the disjoint cell cycle phases at the optimal PDT/TMZ ratio. This effect favors synergism between the PDT and the chemotherapy with TMZ, enhances the antiproliferative effect, and overcomes cross-resistance mechanisms. These results point out that m-NP-based PDT adjuvant therapy is a promising strategy to improve TMZ-based glioblastoma multiforme treatments.