Latest ArticlesNon-nerve cell-derived extracellular matrix (ECM) was coated on the aligned porous polypyrrole-poly(L-lactide) (PPy-PLLA) fiber-films with the conductivity of ~12 mS/m via L929 cells culture and lysing, resulting in~10% increase of PC12 cells attachment and 26 μm increase of neurites length. The neurite length of ~149 μm in EGF/NGF group (optimal concentration radio of 12.5/50 (ng/mL)) on aligned and ECM-conjugated fiber-films was significantly larger than ~94 μm in only NGF group (50 ng/mL), confirming the synergy of EGF, NGF and aligned ECM-conjuaged PPy-PLLA fibers. When differentiated PC12 cells were exerted electrical stimulation (ES) of 100 mV/cm for 4 h/day in 2 day through ECM-PPyPLLA fiber-films, their neurite length reached to ~251 μm, significantly larger than ~149 μm of group without ES, due to the higer expression of related neural proteins in ES group. A simple mechanism was proposed to analyze synergistical effect of ECM, EGF, NGF on axons adhesion and elongation along the aligned ECM-coated fibers under ES condition.
The rigidity of nanoparticles was newly reported to influence their oral delivery. Semi-elastic nanoparticles can enhance the penetration in mucus and uptake by epithelial cells. However, it is still challenging and unclear that the semi-elastic core-shell nanoparticles can enhance the oral bioavailability of peptide drugs. This study was for the first time to validate the semi-elastic coreshell poly(lactic-co-glycolic acid) (PLGA)-lipid nanoparticles (LNPs) as the carrier of the oral peptide drug. The antihypertensive peptide Val-Leu-Pro-Val-Pro (VP5) loaded LNPs (VP5-LNPs) were prepared by a modified thin-film ultrasonic dispersion method. Uptake experiment was performed in Caco-2 and HT-29 cells and monitored by high content screening (HCS) and flow cytometric (FCM). Pharmacokinetics of VP5-LNPs was carried out in Sprague-Dawley (SD) rats and analyzed by DAS 2.0. The optimal VP5-LNPs had an average particle size of 247.3±3.8 nm, zeta potential of -6.57±0.45 mV and excellent entrapment efficiency (EE) of 89.88%±1.23%. Transmission electron microscope (TEM) and Differential scanning calorimeter (DSC) further confirmed the core-shell structure. VP5-LNPs could increase the cellular uptake in vitro and have a 2.55-fold increase in AUC0-72 h, indicating a great promotion of the oral bioavailability. The semi-elastic LNPs remarkably improved the oral availability of peptide and could be a promising oral peptide delivery system for peptide drugs in the future.
We herein propose a co-delivery approach where small interference RNA (siRNA) and anticancer chemotherapeutic drug are simultaneously loaded into a single delivery carrier for the combined treatment of breast cancer and metastasis prevention. The co-delivery vector is composed of chondroitin sulfate (CS)-coated β-cyclodextrin-polyethylenemine polymer, which is capable of loading paclitaxel (PTX) and siRNA simultaneously to form therapeutic nanocomplexes. The nanocomplex, termed as CPPTX-siCD146-CS, is demonstrated to have strong active targeting ability towards CD44-overexpresing breast cancer cells. Moreover, the co-delivery of PTX and siRNA not only effectively inhibits cancer cells proliferation and induces apoptosis, but also well prevents metastasis. Importantly, CP-PTX-siCD146-CS nanocomplexes exhibit stronger cytotoxic effects and anti-metastatic effects on MBA-MD-231 breast cancer cells, in comparison with PTX or siCD146 mono-treatment. The current study defines a potential therapeutic strategy for the combined breast cancer treatment and metastasis prevention from a codelivery perspective.
A friendly biomimetic process was adopted for the mild preparation of "all-inclusive" organic-inorganic nanospheres, which effectively integrate biorecognition function and signal amplification function. The resulted Ca3(PO4)2-Ab2-BSA nanospheres were employed as signal labels for enhancing detection of nuclear matrix protein 22 (NMP 22). The fabricated electrochemical immunosensor exhibited a linear range (0.08-77.00 U/mL) and an ultralow limit of detection (0.01 U/mL) towards NMP 22, which can be taken as a promising tool for clinical diagnosis of bladder cancer.
Herein, we firstly developed a non-covalent glycosylated gold nanoparticles/peptides nanovaccine which is assembled by β-cyclodextrin (β-CD) based host-guest recognitions. This nanovaccine can generate significant titers of antibodies and improve the therapeutic effect against melanoma, suggesting the immunogenicity of peptide antigens can be improved by loading with this carrier. The novel vaccine carrier provides a platform for the transport of various antigens especially T cell-independent antigens.
Core-shell structured mesoporous silica nanoparticles have been firstly synthesized with the new template from L-leucine methyl ester hydrochloride (H-Leu-OMe HCl). LMSNs were characterized by transmission electron microscopy (TEM), nitrogen adsorption/desorption, and small-angle X-ray diffraction (SAXRD), demonstrating a well-ordered mesostructure. After loading doxorubicin hydrochloride (Dox) into pores, considerable loading capacity of 30.5% and favorable cumulative release amount were obtained. MTT assay suggested that Dox-loaded LMSNs demonstrated great promise to anti-tumor. The use of MSNs with the synthesized template, as a drug delivery carrier, will extend the pharmaceutical applications of silica materials.
Near-infrared (NIR) light-triggered photothermal therapy (PTT) is a promising treatment strategy for treating cancer. The combination of nanotechnology and NIR has been widely applied. However, the therapeutic efficacy of the drug-delivery system depends on their ability to avoid phagocytosis of endothelial system, cross the biological barriers, prolong circulation life, localize and rapidly release the therapeutic at target sites. In this work, we designed a platelet membrane (PM)-camouflaged hollow mesoporous bismuth selenide nanoparticles (BS NPs) loading with indocyanine green (ICG) (PM@BS-ICG NPs) to achieve the above advantages. PM-coating has active tumor-targeting ability which could prevent drug leakage and provide drug long circulation, causing drug delivery systems to accumulate in tumor sites effectively. Moreover, as a type of the photothermal sensitizers, BS NPs are used as the inner cores to improve ICG stability and are served as scaffolds to enhance the hardness of this drug delivery system. For one hand, the thermal vibration of BS NPs under NIR laser irradiation causes tumor inhibition through hyperthermia. For another hand, this hyperthermia process could damage PM and let ICG rapid release from PM@BS-ICG NPs. The in vitro and in vivo results showed that this biomimetic nano-drug delivery system exhibits obvious antitumor activity which has good application prospect.
Nanomaterials as drug carriers hold promise for the treatment of carcinomas, but integrating multiple functions into a single vector is difficult. In this study, we aim to develop efficient materials as vectors for co-delivery of microRNA-122 (miR-122) and sorafenib (SRF). We successfully synthesized amphiphilic galactose-modified PEGylated poly(amino-co-ester) (Gal-PEG-PPMS) copolymers consisted of hydrophilic Gal-PEG5k chain segments and hydrophobic poly(ω-pentadecalactone-co-N-methyldiethyleneamine-co-sebacic acid) chain segments, which self-assembled to form cationic micelles at pH 5.2. The results showed that the micelles could encapsulate SRF and bind miR122 simultaneously, increase cellular uptake efficiency. Furthermore, the micelles showed favorable transfection efficiency in enhancing miR122 expression level, the migration and invasion ability of hepatocellular carcinoma (HCC) cells were significantly inhibited after being transfected with miR122-loaded micelles. Most importantly, the co-delivery micelles decreased cell activities of HepG2 cells, which was more effective than miR122 or SRF loaded micelles alone. Collectively, Gal-PEG-PPMS nanoparticles are promising multifunctional carriers for miR122 and SRF co-delivery system to treat HCC.
Cancer therapy with nanoscale drug formulations has made significant progress in the past few decades. However, the selective accumulation and release of therapeutic agents in the lesion sites are still great challenges. To this end, we developed a cRGD-decorated pH-responsive polyion complex (PIC) micelle for intracellular targeted delivery of doxorubicin (DOX) to upregulate tumor inhibition and reduce toxicity. The PIC micelle was self-assembled via the electrostatic interaction between the positively charged cRGD-modified poly(ethylene glycol)-block-poly(L-lysine) and the anionic acid-sensitive 2, 3-dimethylmaleic anhydride-modified doxorubicin (DAD). The decoration of cRGD enhanced the cell internalization of PIC micelle through the specific recognition of αvβ3 integrin on the membrane of tumor cells. The active DOX was released under intracellular acidic microenvironment after endocytosis following the decomposition of DAD. Moreover, the targeted PIC micelle exhibited enhanced inhibition efficacies toward hepatoma in vitro and in vivo compared with the insensitive controls. The smart multifunctional micelle provides a promising platform for target intracellular delivery of therapeutic agent in cancer therapy.
An Ir8Pd4-heteronuclear metal-organic cage (MOC-51) was assembled from bipodal metalloligand[Ir(ppy)2(qpy)(BF4)] (qpy=4, 4':2', 2":4", 4"'-quaterpyridine; ppy=2-phenylpridine) with Pd(Ⅱ) salt. The cubic barrel shaped MOC shows one-photon and two-photon excited deep-red emission, as well as large singlet oxygen quantum yields under visible light irradiation, therefore exhibiting great potentials in organelles-targeted cell imaging and photodynamic therapy (PDT). Compared with the Ir(Ⅲ) metalloligand, the Ir8Pd4-MOC showed less dark toxicity and higher mitochondria-targeting efficiency. The localization in mitochondria overcomes the limitation of short lifetime and diffusion distance of ROS in cell, thus improved PDT effect can be obtained in low light dose usage of the MOC. This study presents the first case of Ir-based metal-organic cages for bio-applications in successful integration of imaging diagnosis and photodynamic therapy
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