Cyanine-Curcumin Assembling Nanoparticles for Near-Infrared Imaging and Photothermal Therapy

Near-infrared (NIR) imaging and photothermal therapy (PTT) based on the multifunctional cyanine dyes has shown great promise for cancer therapy. However, most of the PTT agents are often limited by low drug loading, short circulation time, and low biocompatibility. Herein, we developed cyanine-curcumin assembling nanoparticles (CCNPs) via a single-step reprecipitation method. IR-780-C4 (Cyc4) was employed as a photothermal and NIR imaging agent. Self-assembly of Cyc4 and curcumin in aqueous solution could be performed in the absence of surfactants or adjuvants, which is a simple and efficient way to fabricate nanomedicine with high drug loading. Formed CCNPs showed monodispersity, good stability in physiological conditions, and lower cytotoxicity. Moreover, CCNPs possess the high loading (70%) of cyanine dyes and a higher photothermal conversion efficacy than free Cyc4, which contribute to a decrease in the application dosage of cyanine dyes in cancer therapy. Importantly, CCNPs exhibited excellent NIR imaging capacity and photothermal tumor ablation under laser irradiation in vitro and in vivo. This work highlights the potential of using self-assembling of drug molecules to develop functional nanoparticles for drug delivery and cancer therapy

Cyclodextrin/Paclitaxel Dimer Assembling Vesicles: Reversible Morphology Transition and Cargo Delivery

Here, we developed stable supramolecular binary vesicles on the basis of the host–guest interaction between β-cyclodextrins (β-CDs) and paclitaxel (PTX) dimer. The inclusion complexation between PTX dimer and β-CDs in water was studied by proton nuclear magnetic resonance spectroscopy and two-dimensional rotating-frame Overhauser effect spectroscopy. The resulting inclusion complex was amphiphilic and could self-assemble into vesicles with average diameter of 230 nm. The vesicles could evolve to nanoparticles (NPs) by adding competitive binding guest amantadine hydrochloride or by digesting β-CDs through α-amylase. Moreover, this process was reversible, and the NPs could also transform to vesicles by adding enough β-CDs again. The obtained hollow supramolecular vesicles were further explored to load hydrophilic dye indocyanine green molecule or hydrophobic anticancer drug doxorobicin for their controlled release under external stimulus. This work provides a new strategy for the design of supramolecular systems by using prodrug as building blocks

Redox-Hypersensitive Organic Nanoparticles for Selective Treatment of Cancer Cells

The diselenide-containing fluorescent molecules (SeBDP) and antitumor drug paclitaxel (SePTX) were synthesized and used for constructing SeBDP nanoparticles (SeBDP NPs) and SePTX NPs in aqueous solution through nanoprecipitation method. Both SeBDP NPs and SePTX NPs exhibit high stability and excellent reduction-sensitivity. More interestingly, SeBDP and SePTX could coassemble into uniform and spherical nanoparticles (co-NPs) with dual functions of fluorescence imaging and antitumor activity. These organic NPs could be internalized by different cells as revealed by confocal laser microscopy. Importantly, the co-NPs exhibited selectivity of cytotoxicities between cancerous and normal cells. The cellular proliferation inhibition toward tumor cells (including HeLa and MCF-7 cells) was obviously higher than that toward normal cells (BEAS-2B and L929 cells), which might be attributed to the increasing reactive oxygen species in cancer cells treated by diselenide-containing NPs. These results highlight the potential of developing diselenide-containing organic molecules as molecularly tunable and sensitive nanoplatform for cancer treatment

Blends of Linear and Long-Chain Branched Poly(l‑lactide)s with High Melt Strength and Fast Crystallization Rate

The long-chain branched polylactides (LCB-PLAs) prepared by coupling the hydroxyl-terminated two-arm (linear) and triarm PLA prepolymers of identical arm length with hexamethylenediacianate (HDI) were used to improve the melt rheological and crystallization properties of linear polylactide resin, PLA 4032D from NatureWorks. The blends containing LCB-PLA displayed higher zero shear viscosities, more significant shear shinning, more melt elasticity, and much longer relaxation times together with significant strain hardening in elongational deformation. <i>T</i>_g, <i>T</i>_m and crystallinity (<i>X</i>_c) of linear PLA remained virtually unaffected, but the crystallization rate increased obviously, since the branch points of LCB-PLAs could play a role of nucleating agent. High melt strength, fast crystallization, and favorable miscibility improved the foaming ability of the linear/LCB-PLA blends, substantially

Rheology and Crystallization of Long-Chain Branched Poly(l‑lactide)s with Controlled Branch Length

A series of long-chain branched poly­(l-lactide)­s (LCB-PLAs) with controlled branch length were prepared by a simple and efficient method through a combination of ring-opening polymerization (ROP) of l-lactide and a coupling reaction between the terminal OH groups of the PLA prepolymers and the NCO groups of HDI. The influences of reaction conditions on the synthesis of the LCB-PLAs were investigated, and the structures of the resultant LCB-PLAs were characterized by ¹H NMR spectroscopy and SEC-MALLS. By adjusting the degree of polymerization and the composition of the prepolymers, LCB-PLAs with different branch densities and molecular weights between branch points were obtained. The effect of macromolecular chain branching on the rheology and crystallization of PLA was also investigated. The LCB structure contributed to the enhancement of the zero-shear viscosity, complex viscosity, storage modulus, melt strength, and strain hardening under elongational flow. Thermal behavior indicated that the branch structure resulted in a short nucleation induction period and more rapid crystallization, which can be a guarantee of high-strength foams

Enzyme-Triggered Polyelectrolyte Complex for Responsive Delivery of α‑Helical Polypeptides to Optimize Antibacterial Therapy

Responsive nanomaterials hold significant promise in the treatment of bacterial infections by recognizing internal or external stimuli to achieve stimuli-responsive behavior. In this study, we present an enzyme-responsive polyelectrolyte complex micelles (PTPMN) with α-helical cationic polypeptide as a coacervate-core for the treatment of Escherichia coli (E. coli) infection. The complex was constructed through electrostatic interaction between cationic poly(glutamic acid) derivatives and phosphorylation-modified poly(ethylene glycol)-b-poly(tyrosine) (PEG-b-PPTyr) by directly dissolving them in aqueous solution. The cationic polypeptide adopted α-helical structure and demonstrated excellent broad-spectrum antibacterial activity against both Gram-negative and Gram-positive bacteria, with a minimum inhibitory concentration (MIC) as low as 12.5 μg mL–1 against E. coli. By complexing with anionic PEG-b-PPTyr, the obtained complex formed β-sheet structures and exhibited good biocompatibility and low hemolysis. When incubated in a bacterial environment, the complex cleaved its phosphate groups triggered by phosphatases secreted by bacteria, exposing the highly α-helical conformation and restoring its effective bactericidal ability. In vivo experiments confirmed accelerated healing in E. coli-infected wounds

Chlorophyll content in maize ABA-deficient mutant <i>vp5</i> and wild-type <i>Vp5</i> leaves under normal or dim light

<p>. NL, normal light (control); DL, dim light; NL+D, drought treatment for 8 h under NL conditions. Values are means ± SE (n = 5).</p

Abscisic Acid Refines the Synthesis of Chloroplast Proteins in Maize (<em>Zea mays</em>) in Response to Drought and Light

<div><p>To better understand abscisic acid (ABA) regulation of the synthesis of chloroplast proteins in maize (<em>Zea mays</em> L.) in response to drought and light, we compared leaf proteome differences between maize ABA-deficient mutant <em>vp5</em> and corresponding wild-type <em>Vp5</em> green and etiolated seedlings exposed to drought stress. Proteins extracted from the leaves of <em>Vp5</em> and <em>vp5</em> seedlings were used for two-dimensional electrophoresis (2-DE) and subsequent matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). After Coomassie brilliant blue staining, approximately 450 protein spots were reproducibly detected on 2-DE gels. A total of 36 differentially expressed protein spots in response to drought and light were identified using MALDI-TOF MS and their subcellular localization was determined based on the annotation of reviewed accession in UniProt Knowledgebase and the software prediction. As a result, corresponding 13 proteins of the 24 differentially expressed protein spots were definitely localized in chloroplasts and their expression was in an ABA-dependent way, including 6 up-regulated by both drought and light, 5 up-regulated by drought but down-regulated by light, 5 up-regulated by light but down-regulated by drought; 5 proteins down-regulated by drought were mainly those involved in photosynthesis and ATP synthesis. Thus, the results in the present study supported the vital role of ABA in regulating the synthesis of drought- and/or light-induced proteins in maize chloroplasts and would facilitate the functional characterization of ABA-induced chloroplast proteins in C₄ plants.</p> </div

Light-Activatable Red Blood Cell Membrane-Camouflaged Dimeric Prodrug Nanoparticles for Synergistic Photodynamic/Chemotherapy

Biomimetic approach offers numerous opportunities to design therapeutic platforms with enhanced antitumor performance and biocompatibility. Herein we report red blood cell membrane-camouflaged nanoparticles (RBC­(M­(TPC-PTX))) for synergistic chemo- and photodynamic therapy (PDT). Specifically, the inner core is mainly constructed by reactive oxygen species (ROS)-responsive PTX dimer (PTX₂-TK) and photosensitizer 5,10,15,20-tetraphenylchlorin (TPC). <i>In vitro</i> experiments show that the prepared RBC­(M­(TPC-PTX)) is readily taken up into endosomes. Under appropriate light irradiation, the TPC can generate ROS, not only for PDT but also for triggering PTX₂-TK cleavage and on-demand PTX release for chemotherapy. <i>In vivo</i> results show that the coating of RBC membrane prolongs blood circulation and improves tumor accumulation. The combination of chemo- and photodynamic therapy enhances anticancer therapeutic activity, and light-triggered drug release reduces systematic toxicity. All these characteristics render the described technology extremely promising for cancer treatment

Transferrin-Conjugated Micelles: Enhanced Accumulation and Antitumor Effect for Transferrin-Receptor-Overexpressing Cancer Models

As the transport protein for iron, transferrin can trigger cellular endocytosis once binding to its receptor (TfR) on the cell membrane. Using this property, we conjugated transferrin onto the surface of biodegradable polymeric micelles constructed from amphiphilic block copolymers. The core of micelle was either labeled with a near-infrared dye (NIR) or conjugated with a chemotherapeutic drug paclitaxel (PTX) to study the biodistribution or antitumor effect in nude mice bearing subcutaneous TfR-overexpressing cancers. DLS and TEM showed that the sizes of Tf-conjugated and Tf-free micelles were in the range of 85–110 nm. Confocal laser scanning microscopy and flow cytometry experiments indicated that the uptake efficiency of the micelles by the TfR-overexpressing cells was enhanced by Tf conjugation. Semiquantitative analysis of the NIR signals collected from the tumor site showed that the maximum accumulation was achieved at 28 h in the M­(NIR) group, while at 22 h in Tf–M­(NIR) groups; and the area under the intensity curve in the Tf–M­(NIR) groups was more than that in M­(NIR) group. Finally, the tumor inhibition effects of targeting micelles were studied with the gastric carcinoma model which overexpressed TfR. The analysis of tumor volumes and the observation of H&E-stained tumor sections showed that Tf–M­(PTX) had the best antitumor effect compared with the control groups (saline, PTX, and M­(PTX)). The results of this study demonstrated the potential application of Tf-conjugated polymeric micelles in the treatment of TfR-overexpressing cancers