Latest ArticlesThe goal of the present study is to elucidate the intragastrointestinal fate of micellar delivery systems by monitoring fluorescently labeled different micelles and the model drug paclitaxel (PTX). Both in vitro and ex vivo leakage studies showed fast PTX release in fluids while micelles remained intact, except in fed-state simulated intestinal fluid and fasted-state pig intestinal fluid, thus referring to the intact absorption of micelles and PTX leakage in the gastrointestinal tract with d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) micelles showing higher stability than other micelles. All groups of micelles were absorbed intact in Caco-2 and Caco-2/HT29-MTX cell models and the absorption of TPGS micelles was found to be higher than other micelles. The transport of the micelles across Caco-2/Raji (1.6%–3.5%), Caco-2 (0.8%–1%), and Caco-2/HT29-MTX (0.58%–1%) cell monolayers further verified the absorption of micelles and their subsequent transport; however, more TPGS micelles transported across cell monolayers than other groups. Moreover, the histological examination also confirmed that micelles entered the enterocytes and were transported to basolateral tissues and TPGS showed the stronger ability of penetration than other groups. Thus, these results are succinctly presenting the absorption of intact micelles in GIT confirmed by imaging evidence with prior leakage of the drug, uptake by enterocytes and the transport of micelles that survive the digestion by enterocytes and mainly by microfold cells in material nature dependent way with TPGS showing better results than other groups. In conclusion, these results identify the mechanism by which the gastrointestinal tract processes micelles and point to the likely use of this approach in the design of micelles-based therapies.
As a vital nutrient closely related to the cancer-cells proliferation, phosphate anions have been paid great attention as a promising anticancer agent. Generally, the transport of phosphate anions depends on a protein transport system which is regulated by ion homeostasis regulations. Herein, we designed a reactive anionic nanocarrier based on black phosphorus nanosheets (BPs) and artesunate (ART), which could enter cells through endocytosis to generate phosphate anions, avoiding the regulation of cell homeostasis. The ionic nanocarrier was coated by polydopamine to defend BPs and ART and functionalized by folate (FA) and hyaluronic acid (HA) for targeting factor. With the anchoring groups FA/HA targeted the carrier into cells, polydopamine coating decomposed to expose ART for further generating reactive oxygen species (ROS) in cancer cell microenvironment, providing oxidation conditions. Next, ROS generated by ART makes BPs decompose to phosphate anions with effectively speed, giving rise to the destruction of ion homeostasis to induce necrosis and inhibit the proliferation for cancer cells. In consequence, this research provides novel idea and direction for the ionic carriers and tumor therapeutics.
This device is aimed at ensuring that the sample is uniformly and equivalently reacted with the antibody on the NC membrane in each test when the microfluidic liquid system is introduced to the chip. In this study, the developed microfluidic chip can avoid the presence of the sample and conjugate pads in the chip, while the precision of the chromatography system can be greatly improved using the same particles, NC membrane and antibody alongside the traditional strip. The results, taking the detection of cTnI as an example, revealed that the coefficient of variation (CV) is controlled within 4%, while the maximum record of the contrast chromatographic reagent strip can reach 15%. Additionally, the detection sensitivity can maintain the same order of magnitudes with that of the traditional chromatographic strip. With the results, the determination correlation of the developed microfluidic chip has been greatly improved. In addition, the CV of the chip in this study is greatly improved in comparison with that of the traditional strip. The biggest improvement lies in the mixing between the sample and the microspheres, indicating that this is a new approach to improve the CV of the traditional strip.
Delivery systems based on nanoparticles (NPs) have shown great potential to reduce side effects and improve the therapeutic efficacy. Herein, we report the one-pot synthesis of poly(ethylene glycol)-mediated zeolitic imidazolate framework-8 (ZIF-8) NPs for the co-delivery of an anticancer drug (i.e., doxorubicin) and a cell penetrating peptide containing histidine and arginine (i.e., H4R4) to improve the efficacy of therapeutic delivery. The cargo-encapsulated ZIF-8 NPs are pH-responsive, which are stable at neutral pH and degradable at acidic pH to release the encapsulated cargos. The released H4R4 can help for endosome/lysosome escape to enhance the cytotoxicity of the encapsulated drugs. In vivo studies demonstrate that the co-delivery of doxorubicin and H4R4 peptides can efficiently inhibit tumor growth without significant side effects. The reported strategy provides a new perspective on the design of drug delivery systems and brings more opportunities for biomedical applications.
As a potent anticancer drug, gambogic acid (GA) suffers from its poor water solubility and low chemical stability and shows a limited clinical outcome. To address this problem, we report here a simple and effective strategy to immobilize and deliver GA using a reducible diblock poly(amino acid) as a model. The electrostatic interaction between GA and polymer enables a high drug loading content up to 53.6 %. Moreover, the drug complexation induces a micelle-to-vesicle transformation, combined with a conformation transition from random coil to α-helix. The hierarchically assembled drug nanocomplexes can serve as a smart carrier for efficient cell internalization and triggered release of multiple drugs under intracellular acidic and reductive conditions, resulting in a synergistic antitumor efficacy in vitro. This work provides a new insight into the drug-carrier interaction and a facile nanoplatform for drug delivery applications.
Although titanate nanofibers (TiNFs) and titanate nanotubes (TiNTs) have been proposed as relatively biocompatible nanomaterials (NMs), there is currently lacking of systemic studies which investigated the toxicity of TiNFs and TiNTs to endothelium. In this study, we developed endothelial monolayer model by using cell culture inserts, and systemically investigated the toxicity of TiNFs and TiNTs by RNA-seq, with a focus on Kruppel-like factor (KLF)-mediated effects, since KLF are transcription factors (TF) involved in the regulation of vascular biology. It was shown that NMs did not significantly induce cytotoxicity despite substantial internalization. However, the expression of many KLF was altered, and Western blot further confirmed that NMs down-regulated KLF2 proteins. Ingenuity pathway analysis (IPA) revealed that NMs altered the expression of KLF2-targed genes, typically the genes involved in inflammatory responses. KLF2-related Gene Ontology (GO) terms and Kyoto Encyclopedia of Gene and Genomes (KEGG) pathways were also altered, and it should be noticed that NMs altered GO terms and KEGG pathways related with endothelial NO synthase (eNOS). This study further verified that NMs decreased intracellular NO and eNOS proteins. All the observed effects were more obvious for TiNFs compared with TiNTs. Combined, this study showed that TiNFs or TiNTs were non-cytotoxic to endothelial monolayer model, but TiNFs and more modestly TiNTs decreased KLF2 leading to decreased eNOS proteins and NO production. Our data may provide novel understanding about the toxicity of TiNFs as well as other Ti-based NMs to endothelium.
Herein, we utilized nucleic acids induced peptide co-assembly strategy to develop novel nucleic acids induced peptide-based AIE (NIP-AIE) nanoparticles. Strong fluorescent of AIE could be observed when a little amount of nucleic acids was added into the peptide solution, and the intensity could be regulated by the concentration of nucleic acids. This AIE nanoparticle with good biocompatibility could achieve fast cell imaging. It is also proved that the fluorescence intensity of AIE decreased with time, which indicates that the reducible cross-linkers of Wpc peptide by GSH and nanoparticles gradually disintegrate in cell. Based on the different of AIE fluorescence signals which regulated by the formation and disintegration of nanoparticles, this AIE system is expected to be used for real-time monitoring of drug release from peptide-based nano carriers in vivo or in vitro, and may provide a new platform for the construction of other organic AIE nanoparticles.
We describe an application of carrier protein-free strategy in constructing a fully synthetic methamphetamine (METH) vaccine that contains three components: Toll-like receptor 2 ligand, Th2 epitope, and METH hapten. The immunological evaluation in mice revealed high titers of METH-specific antibodies induced by the construct and the activation of humoral immunity that would be beneficial for neutralization and clearance of the METH molecule. Behavioral experiments indicated that the synthetic vaccine attenuated the acquisition of METH-induced conditioned place preference and inhibited the initiation and expression of METH-induced locomotor sensitization. These results demonstrate that the lipopeptide-based vaccine has invoked an immune response and showed the potential of preventing the rewarding and psychoactive effects of METH.
Near-infrared (NIR) small molecular organic dyes as photothermal agents for cancer photothermal therapy (PTT) have attracted considerable research attention. Herein, two donor-acceptor-donor (D-A-D) structured NIR dyes, BBTT and SeBTT, are rationally designed, where the only difference is one heteroatom within the acceptor unit varying from sulfur to selenium (Se). More importantly, SeBTT NPs exhibit stronger NIR absorbance and higher photothermal conversion efficiency (PTCE ≈ 65.3%). In vivo experiments illustrate that SeBTT NPs can be utilized as a high contrast photoacoustic imaging (PAI) agent, and succeed in tumor suppression without noticeable damage to main organs under NIR photoirradiation. This study presents an effective molecular heteroatom surgery strategy to regulate the photothermal properties of NIR small molecules for enhanced PAI and PTT.
With excellent biocompatibility and biodegradability, natural polysaccharides and their derivatives have exhibited great potential in constructing drug delivery vehicles for tissue engineering and therapeutics. Cucurbit[n]uril (CB[n])-mediated reversible crosslinking of polysaccharides possess intrinsic stimuli-responsiveness towards competitive guests and have been extensively investigated to fabricate various particles and hydrogels for multiple stimuli-responsive drug release by incorporation with other stimuli including photo, redox, and enzyme. Through host-guest interactions between CB[6] and aliphatic diamines, functional tags covalently connected with CB[6] can be readily anchored into polysaccharide-based hydrogels, realizing multiple functionalization. The rheological property and drug release profile of polysaccharide-based supramolecular hydrogels can be facilely tuned through CB[8]-mediated dynamic homo or hetero crosslinking of polysaccharides and/or other polymers. In this review, we introduce and summarize recent progress regarding polysaccharide-based supramolecular drug delivery systems mediated via host-guest interactions of CB[6] and CB[8], covering both bulk hydrogels and particular systems. At the end, possible utilization of CB[7]-based host-guest interactions in constructing polysaccharide-based drug delivery systems and future perspectives of this research direction are also discussed.
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