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Plot of fluorescence intensity (627 nm) of NR vs concentration of OEG-DPH with the excitation wavelength at 550 nm (a). Inserted photograph shows the solutions of NR with OEG-DPH; Fluorescence emission spectra (b) and UV-vis spectra (c) of NR dispersing in the OEG-DPH solutions with different concentrations. Plot of intensity ratio of A578 to A538 vs different concentration of OEG-DPH (d). The bottom scheme showed the simulation of NR loading in micelles (I: 0.01–0.05 mg/mL; II: 0.05 mg/mL; III: 0.05–0.3 mg/mL).
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Here we presented a novel micelle self-assembled from amphiphiles with π-conjugated moieties (OEG-DPH). The π-conjugated structural integrity of the micelles enabled stable encapsulation of Nile Red (NR, model drug). The self-assembly behaviour of the amphiphiles and the release profile of NR loaded micelles were investigated. Spherical core-shell...
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![FIG. 2. A snapshot of a typical double emulsion (from Ref. [5]).](profile/Giuseppe-Pontrelli-3/publication/340618312/figure/fig6/AS:992833670488065@1613721401303/A-snapshot-of-a-typical-double-emulsion-from-Ref-5_Q320.jpg)
We present a mechanistic model of drug release from a multiple emulsion into an external surrounding fluid. We consider a single multi-layer droplet where the drug kinetics are described by a pure diffusive process through different liquid shells. The multi-layer problem is described by a system of diffusion equations coupled via interlayer conditi...
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... The development of nanotechnology has brought a new dawn to the treatment of diseases such as cancer [1][2][3][4][5]. Nano-drug delivery systems have received extensive attention because of their improved pharmacokinetics, tumor-targeted delivery, and low drug toxicity. ...
We developed a pH/GSH dual-responsive smart nano-drug delivery system to achieve targeted release of a chemotherapeutic drug at breast tumor site. Doxorubicin (DOX) was linked to polyethylene glycol through cis-aconitic anhydride and disulfide bonds to obtain the PEG-SS-CA-DOX prodrug, which spontaneously assembled into nanomicelles with a particle size of 48±0.45 nm. PEG-SS-CA-DOX micelles achieved an efficient and rapid release of DOX under dual stimulation by weak acidic pH and high GSH content of tumors, with the release amount reaching 88.0% within 48 hours. Cellular uptake experiments demonstrated that PEG-SS-CA-DOX micelles could efficiently transport DOX into cells and rapidly release it in the tumor microenvironment. In addition, in vivo antitumor experiments showed that PEG-SS-CA-DOX had a high inhibition rate of 70% against 4T1 breast cancer cells along with good biosafety. In conclusion, dual-responsive smart nanomicelles can achieve tumor-targeted drug delivery and specific drug release, thus improving therapeutic efficacy of drugs.
... Next, the minimum concentration of AG-08 required for the particle formation was determined by using Nile red staining. Nile red is widely used to monitor supramolecular structures such as micelles or aggregates as it is nearly non-fluorescent in aqueous conditions but tends to associate with hydrophobic domain within the assemblies and emits intense fluorescence 13,14 . The critical assembly concentration of AG-08 was found to be approximately 2 µM (Fig. 1C). ...
The discovery of novel chemotherapeutics that act through different mechanisms is critical for dealing with tumor heterogeneity and therapeutic resistance. We previously reported a saponin analog (AG-08) that induces non-canonical necrotic cell death and is auspicious for cancer therapy. Here, we describe that the key element in triggering this unique cell death mechanism of AG-08 is its ability to form supramolecular particles. These self-assembled particles are internalized via a different endocytosis pathway than those previously described. Microarray analysis suggested that AG-08 supramolecular structures affect several cell signaling pathways, including unfolded protein response, immune response, and oxidative stress. Finally, through investigation of its 18 analogs, we further determined the structural features required for the formation of particulate structures and the stimulation of the unprecedented cell death mechanism of AG-08. The unique results of AG-08 indicated that supramolecular assemblies of small molecules are promising for the field of anticancer drug development, although they have widely been accepted as nuisance in drug discovery studies.
Long-distance transmission of oil is usually carried out in large-diameter steel pipelines; water present therein may cause severe internal corrosion. An effective method of mitigating such corrosion is to inject organic corrosion inhibitors (CIs). Their surface adsorption, via heteroatom functionalities, can markedly enhance the corrosion resistance of metals. In this study, three CI model compounds with different head groups but the same alkyl tail length (-C14H29), specifically tetradecyltetrahydropyrimidinium (THP-C14), tetradecylphosphate ester (PE-C14) and tetradecylimidazolinium (IMID-C14) were synthesized, their purities being determined using nuclear magnetic resonance spectroscopy (NMR). The critical micelle concentrations (CMCs) of each compound were measured using surface tensiometry (Du Noüy ring) and fluorescence spectroscopy techniques, differences being found between these indirect and direct methods. In addition, linear polarization resistance was used to determine inhibition efficiencies (IEs) for carbon steel immersed in a 5 wt.% NaCl electrolyte saturated with CO2. CI surface saturation concentrations, with maximum IEs, were compared with the determined CMCs. Excellent IEs were observed at concentrations of THP-C14, PE-C14 and IMID-C14 which do not correspond with their CMCs, the differences involved being significantly greater than what has previously been reported for tetradecylbenzyldimethylammonium (BDA-C14). These results demonstrate that there is no direct link between CMC and metal surface saturation/corrosion inhibition efficiency that can be made on a generalized basis for the different head groups but with the same tail length corrosion inhibitors, indicating that the selection of the appropriate CI concentration for an industrial application should not be based on CMC alone.
A novel hollow polypyrrole coated by mesoporous silica nanoparticles graft poly(2-(4-formylbenzoyloxy)ethyl methacrylate-co-2-(dimethylamino)ethyl methacrylate)-block-poly(triethylene glycol methyl ether methacrylate) multifunctional nanocomposite ([email protected]g-P(FBEMA-co-DMAEMA)-b-PTEGMA) was designed and prepared via disulfide bond linkages. This material as a gatekeeper integrated multifunctionality such as pore capping, and pH and potothermal multistimuli response abilities, and possessed good photothermal stability, near-infrared (NIR) photothermal conversion capacity and dispersion stability in aqueous solution. It could entrap anticancer doxorubicin (DOX) by pore channels of [email protected], the core of amphiphilic copolymer micelles and Schiff base linkages, offering a load capacity and load efficiency of up to about 41.5 and 83.1%, respectively. Dynamic light scattering analysis showed that the DOX-loaded preparations had particle size of less than 300 nm, and could achieve intracellular chemo–photothermal combination therapy by controlling the mesopore on-off based on the gatekeepers, tumor environments including pH and reductant stimuli. The drug-loaded nanoparticles exhibited optimal drug release dynamics in cancer tissues upon triggered by pH and glutathione (GSH) under the NIR irradiation. Cell counting Kit-8 assay manifested that the nanocarriers are non-toxic and safe, whereas the drug-loaded preparations exhibited robust anticancer efficacy. Cellular uptake and TUNEL assay revealed high concentrations of DOX accumulating around and inside Hela cells, accordingly producing significant tumor cell apoptosis. Therefore, the newly-developed materials can be used for comprehensive therapy of cancer as a promising candidate of drug delivered carriers.
End-group functionalization of homopolymers is a valuable way to produce high-fidelity nanostructured and functional soft materials when the structures obtained have the capacity for self-assembly (SA) encoded in their structural details. Herein, an end-functionalized PCL with a π-conjugated EDOT moiety, (EDOT-PCL), designed exclusively from hydrophobic domains, as a functional “hydrophobic amphiphile”, was synthesized in the bulk ROP of ε-caprolactone. The experimental results obtained by spectroscopic methods, including NMR, UV-vis, and fluorescence, using DLS and by AFM, confirm that in solvents with extremely different polarities (chloroform and acetonitrile), EDOT-PCL presents an interaction- and structure-based bias, which is strong and selective enough to exert control over supramolecular packing, both in dispersions and in the film state. This leads to the diversity of SA structures, including spheroidal, straight, and helical rods, as well as orthorhombic single crystals, with solvent-dependent shapes and sizes, confirming that EDOT-PCL behaves as a “block-molecule”. According to the results from AFM imaging, an unexpected transformation of micelle-type nanostructures into single 2D lamellar crystals, through breakout crystallization, took place by simple acetonitrile evaporation during the formation of the film on the mica support at room temperature. Moreover, EDOT-PCL’s propensity for spontaneous oxidant-free oligomerization in acidic media was proposed as a presumptive answer for the unexpected appearance of blue color during its dissolution in CDCl3 at a high concentration. FT-IR, UV-vis, and fluorescence techniques were used to support this claim. Besides being intriguing and unforeseen, the experimental findings concerning EDOT-PCL have raised new and interesting questions that deserve to be addressed in future research.
Skin cancer is one of the most common types of cancer in the United States and worldwide. Topical products are effective for treating cancerous skin lesions when surgery is not feasible. However, current topical products induce severe irritation, light-sensitivity, burning, scaling, and inflammation. Using hyaluronic acid (HA), we engineered clinically translatable polymer-drug conjugates of doxorubicin and camptothecin termed, DOxorubicin and Camptothecin Tailored at Optimal Ratios (DOCTOR) for topical treatment of skin cancers. When compared to the clinical standard, Efudex, DOCTOR exhibited high cancer-cell killing specificity with superior safety to healthy skin cells. In vivo studies confirmed its efficacy in treating cancerous lesions without irritation or systemic absorption. When tested on patient-derived primary cells and live-skin explants, DOCTOR killed the cancer with a selectivity as high as 21-fold over healthy skin tissue from the same donor. Collectively, DOCTOR provides a safe and potent option for treating skin cancer in the clinic.
Lots of efforts have been devoted to enhancing the antitumor efficacy of reactive oxygen species (ROS)‐responsive nanoscale drug delivery systems. Here, a ROS‐responsive amphiphilic polymer (mPEG‐b‐poly(thioacetal‐thioether), P2) with property of generation and self‐sustained high level of ROS, and a control material mPEG‐b‐poly(ester‐thioether) (P1) were constructed and characterized by proton nuclear magnetic resonance (¹H NMR). The two polymers could self‐assemble into micelles and the doxorubicin loading content of P1 and P2 micelles were 13.08 % and 13.51 %, respectively. The two polymers could self‐assemble into micelles and exhibit good DOX loading capacity. ROS‐responsiveness of P1 and P2 micelles was investigated by¹H NMR, dynamic light scattering (DLS), and scanning electron microscope (SEM). The results of in vitro ROS detection indicated that P2 micelles could ROS‐responsive release of cinnamaldehyde, and promote intracellular generation of ROS and maintain high level of ROS. DOX/P1 micelle shown comparable in vitro antitumor efficacy with DOX/P2 micelle, and a slightly lower IC50 value was due to DOX/P1 micelle has faster cell internalization, poorer micelle stability and integrality. Considering the stability of the nanoparticle circulation in vivo, the DOX/P2 micelle containing both thioether and thioacetal would be more suitable and could show better in vivo antitumor efficacy.
Prodrug nanoparticles with cleavable moieties sensitive to intracellular stimuli have drawn great attention on cancer chemotherapy. Herein, a reactive oxygen species (ROS)-responsive doxorubicin prodrug mPEG-Phe-TK-Phe-hyd-DOX was synthesized, in which hydrophilic methoxy poly(ethylene glycol) (mPEG) and hydrophobic anticancer drug doxorubicin (DOX) were conjugated with hydrazone (hyd) and ROS-responsive thioketal (TK) moieties. The ROS-responsiveness of prodrug was confirmed by proton nuclear magnetic resonance (¹H NMR) and dynamic light scattering (DLS). Unexpectedly, the results of in vitro drug release indicated that the hydrazone bond of prodrug nanoparticles was insensitive to pH, which may be due to the strong hydrophobicity, π-π interactions and cation-π interactions jointly inhibited the hydrolysis of hydrazone bonds under acidic conditions. The cellular uptake and in vitro anticancer study showed that ROS-responsive prodrug nanoparticles exhibited faster cellular uptake and better anticancer efficacy. The in vivo experiments showed that the ROS-responsive prodrug nanoparticles had comparable antitumor efficacy with free anticancer drug DOX and reduced organ toxicity. Our results provide novel idea of successfully design multi-stimuli-responsive nano-drug carrier.
Amphiphilic mPEG-modified peptide nanoparticles were developed from oligo-phenylalanine (OPhe) nanoparticles (NPs) synthesized via papain. Tyndall effects indicate that OPhe NPs are amphiphobic. Addition of protein perturbants, sodium dodecyl sulfate (SDS), and urea, in the dispersion solution of OPhe NPs can significantly reduce the Rh,m value of NPs, from approximately 749.2 nm to about 200 nm. Therefore, the hydrophobic interaction and hydrogen bonding play major roles in maintaining the aggregation of OPhe NPs. Using the “grafting to” method, the methoxypolyethylene-modified OPhe NPs (mPEG-g-OPhe NPs) were synthesized and characterized by Fourier transform infrared spectroscopy (FTIR), ¹H NMR, electrospray ionization mass spectrometry (ESI-MS), and dynamic light scattering (DLS). The attenuated total reflectance (ATR) spectrum of OPhe NPs and mPEG-g-OPhe NPs demonstrate that the secondary structures of these NPs are mainly β-type. mPEG-g-OPhe NPs can self-aggregate into spherical micelles both in water and cyclohexane. Increasing the chain length of the mPEG moiety, the critical micellar concentrations of mPEG-g-OPhe NPs increased in water but decreased in cyclohexane. The light stability, thermal stability, hydrolysis stability, and encapsulation stability of curcumin were significantly promoted by encapsulation in the micelles formed by mPEG-g-OPhe NPs. The protective effects regularly varied with the variations in the mPEG chain length of mPEG-g-OPhe NPs.
