Extraction and composition characterisation of amino acids from tung meal

<p>The most desirable content of amino acids (AAs) in the extracted products from tung (<i>Aleurites fordii</i>) meal was 93.88%, which was obtained from shelled tung meal at a hydrolysis temperature of 45°C and a isoelectric precipitation pH value of 4.4. Furthermore, the cytotoxic activity of extracted AAs was also evaluated by MTT assay. Antioxidant activity of extracted AAs was also measured by the DPPH assay. As a result, the high yield of extracted AAs exhibited so low cytotoxic and high antioxidant activity that had the potential use as a functional ingredient.</p

Precise Control of Shape-Variable Nanomicelles in Nanofibers Reveals the Enhancement Mechanism of Passive Delivery

Nowadays, the development of nanoparticles is known to be mainly associated with enhancement of the targeted delivery of the active component to solid tumors. However, the lack of understanding of the nanoparticle morphology restricts the transport efficiency of various nanocarriers, especially offers no consistent mechanism for the delivery. Here, we demonstrate the principles of enhancement of passive delivery utilizing the precise control and analysis of shape-switchable nanomicelles without any functional addition. We successfully regulated the nanomicelle shape with various aspect ratios in the electrospun nanofiber matrix and devised a stretching phase diagram. Using the vascular leakage model, visual laser spectrum, and image analysis in the simulated scene, we found that the deformed nanomicelles with high aspect ratios along with lower equivalent volumes were significantly beneficial to the passive delivery. Further, the enhanced permeability of the shape-variable nanomicelles in the recovering state was up to 4 times of that observed before recovery. Our results challenge the current consensus of passive targeting and provide an important guidance for the design of nanoparticle morphology and active addition in cancer nanomedicine

Supercooling Self-Assembly of Magnetic Shelled Core/Shell Supraparticles

Molecular self-assembly has emerged as a powerful technique for controlling the structure and properties of core/shell structured supraparticles. However, drug-loading capacities and therapeutic effects of self-assembled magnetic core/shell nanocarriers with magnetic nanoparticles in the core are limited by the intervention of the outer organic or inorganic shell, the aggregation of superparamagnetic nanoparticles, the narrowed inner cavity, etc. Here, we present a self-assembly approach based on rebalancing hydrogen bonds between components under a supercooling process to form a new core/shell nanoscale supraparticle with magnetic nanoparticles as the shell and a polysaccharide as a core. Compared with conventional iron oxide nanoparticles, this magnetic shelled core/shell nanoparticle possesses an optimized inner cavity and a loss-free outer magnetic property. Furthermore, we find that the drug-loaded magnetic shelled nanocarriers showed interesting <i>in vitro</i> release behaviors at different pH conditions, including “swelling-broken”, “dissociating-broken”, and “bursting-broken” modes. Our experiments demonstrate the novel design of the multifunctional hybrid nanostructure and provide a considerable potential for the biomedical applications

Shape Memory Actuation of Janus Nanoparticles with Amphipathic Cross-Linked Network

Preparation of nanoscale Janus particles that can respond to external stimulation and, at the same time, be prepared using an easily achievable method presents a significant challenge. Here, we have demonstrated the shape memory of Janus nanoparticles (SMJNPs) with a multifunctional combination of Janus nanostructure and a shape memory effect, composed of a well-defined amphipathic sucrose-poly­(ε-caprolactone) cross-linked network. A sudden negative pressure method was first used to prepare the Janus-shaped nanoparticles (temporary shape), which can switch their shape and wettability. The Janus-shaped nanoparticle is an amphipathic structure composed of hydrophilic and hydrophobic parts. Moreover, in response to temperature, the nanoparticle can recover their nanosphere state via a shape memory process. The novel Janus nanoparticles with the shape memory property also show a great potential for application such as drug delivery

Folate Decoration Supports the Targeting of Camptothecin Micelles against Activated Hepatic Stellate Cells and the Suppression of Fibrogenesis

As the central cellular player in fibrogenesis, activated hepatic stellate cells (aHSCs) are the major target of antifibrotic nanomedicines. Based on our finding that activated HSCs increase the expression of folate receptor alpha (FRα), we tried to apply folic acid (FA) decoration to generate an active drug-targeting at aHSCs and suppress hepato-fibrogenesis. FA-conjugated poly­(ethylene glycol)-poly­(ε-caprolactone) copolymers (PEG-PCL) were synthesized and self-assembled into the spherical micelles that owned a uniform size distribution averaging at 60 nm, excellent hemo- and cyto-compatibility, and pH-sensitive stability. These FA-modified micelles were preferentially ingested by aHSCs as expected and accumulated more in acutely CCl4 injured mouse livers compared to nondecorated counterparts. Such an aHSC targetability facilitated the loaded medicinal camptothecin (CPT) to achieve a greater therapeutic efficacy and inhibition of MF phenotypic genes in aHSCs. Encouragingly, though free CPT and nontargeting CPT micelles produced negligible curative outcomes, FA-decorated CPT micelles yielded effectively remedial effects in chronically CCl4-induced fibrotic mice, as represented by a significant shrinkage of aHSC population, suppression of fibrogenesis, and recovery of liver structure and function, clearly indicating the success of the folate decoration-supported aHSC-targeted strategy for antifibrotic nanomedicines in fibrosis resolution

Pulse Electrochemical Driven Rapid Layer-by-Layer Assembly of Polydopamine and Hydroxyapatite Nanofilms via Alternative Redox <i>in Situ</i> Synthesis for Bone Regeneration

Polydopamine (PDA) is an important candidate material for the surface modification of biomedical devices because of its good adhesiveness and biocompatibility. However, PDA nanofilms lack osteoinductivity, limiting their applications in bone tissue engineering. Hydroxyapatite nanoparticles (HA-NPs) are the major component of natural bone, which can be used to effectively enhance the osteoinductivity of PDA nanofilms. Herein, we developed a pulse electrochemical driven layer-by-layer (PED-LbL) assembly process to rapidly deposit HA-NPs and PDA (HA-PDA) multilayer nanofilms. In this process, PDA and HA-NPs are <i>in situ</i> synthesized in two sequential oxidative and reductive pulses in each electrochemical deposition cycle and alternately deposited on the substrate surfaces. PDA assists the <i>in situ</i> synthesis of HA-NPs by working as a template, which avoids the noncontrollable HA nucleation and aggregation. The HA-PDA multilayer nanofilms serve as a tunable reservoir to deliver bone morphogenetic protein-2 and exhibit high osteoinductivity both <i>in vitro</i> and <i>in vivo</i>. This PED-LbL assembly process breaks the limitation of traditional LbL assembly, allowing not only the rapid assembly of oppositely charged polyelectrolytes but also the <i>in situ</i> synthesis of organic/inorganic NPs that are uniformly incorporated in the nanofilm. It has broad applications in the preparation of versatile surface coatings on various biomedical devices

Isolation and Sequencing of Salsolinol Synthase, an Enzyme Catalyzing Salsolinol Biosynthesis

Salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline), a derivate of dopamine, is suspected to be the most probable neurotoxin in the degeneration of dopaminergic neurons. Numerous hypotheses regarding its pathophysiological roles have been raised, especially related to Parkinson’s disease and alcohol addiction. In the mammalian brain, salsolinol may be enzymatically synthesized by salsolinol synthase from dopamine and acetaldehyde. However, the direct evidence of its biosynthesis was still missing. In this study, we purified salsolinol synthase from rat brain by a systematical procedure involving acid precipitation, ultrafiltration, and hydrophilic interaction chromatography. The molecular weight of salsolinol synthase determined by MALDI-TOF MS is 8622.29 Da, comprising 77 amino acids (MQIFVKTLTG KTITLEVEPS DTIKNVKAKI QDKEGIPPDQ QRLIFAGKQL EDGRTLSDYN IQKKSTLHLV LRLRVDY). Homology analysis showed that the enzyme is a ubiquitin-like protein, with a difference of four amino acids, which suggests it is a novel protein. After it was overexpressed in eukaryotic cells, the production of salsolinol was significantly increased as compared with control, confirming the catalytic function of this enzyme. To our knowledge, it is the first systematic purification and sequencing of salsolinol synthase. Together, this work reveals a formerly anonymous protein and urges further exploration of its possible prognostic value and implications in Parkinson’s disease and other related disorders