Design and construction of IR780- and EGCG-based and mitochondrial targeting nanoparticles and their application in tumor chemo-phototherapy.

An integration combination of phototherapy and chemotherapy to treat carcinoma, solving the inner limitation of individual-modal chemical agent-based therapy or phototherapy, emerges to be a strategy with high prospects for achieving synergistic curative effects. The dye IR780-iodide (IR780) close to infrared radiation is a phototherapy agent with high prospects. However, it is limited in its clinical applications due to poor solubility in water. While epigallocatechin-3-gallate (EGCG), naturally resourced green tea polyphenol, has been extensively proven with intrinsic antitumor activity, but it is largely restricted by its low bioavailability in vivo. Hence, novel multiple-function nanoparticles comprising hyaluronic acid (HA) and IR780 were proposed to deliver EGCG, defined as EGCG@THSI nano-scale particles (EGCG@THSI NPs), thereby rapidly solving limitations of EGCG and IR780. Amphiphilic nano-scale carrier was prepared by triphenylphosphine (TPP), hyaluronic acid (HA), cystamine, and IR780, termed as TPP-HA-SS-IR780, and EGCG was loaded into the amphiphilic copolymer by self-assembly. TPP-HA-SS-IR780 endowed the as-synthesized EGCG@THSI NPs with excellent TPP-mediated mitochondrial-targeted and glutathione-triggered rapid drug release properties. As impacted by the integration of phototherapy and chemotherapy, the EGCG@THSI NPs under NIR laser irradiation showed a prominent anti-tumor effect. Taken together, this study presented a multiple-function nano-scale carrier platform with high prospects in improving the therapeutic efficacy of anti-carcinoma drugs.

Structural characteristics and in vitro and in vivo immunoregulatory properties of a gluco-arabinan from Angelica dahurica.

A water-soluble polysaccharide identified here as ADP80-2 was acquired from Angelica dahurica. ADP80-2 was a gluco-arabinan composed of arabinose and a trace of glucose with a molecular weight of 9950 g/mol. The backbone of ADP80-2 comprised →5)-α-L-Araf-(1→, →3, 5)-α-L-Araf-(1→, →6)-α-D-Glcp-(1→, with a terminal branch α-L-Araf-(1 → residue. In terms of immunoregulatory activity, ADP80-2 can significantly promote the phagocytosis, the production of nitric oxide (NO), and the secretion of cytokines (IL-6, IL-1ß, and TNF-α) of macrophage. In addition to the cellular immunomodulatory activities, the chemokines related to immunoregulation were significantly increased in the zebrafish model after treated with ADP80-2. These biological results indicated that ADP80-2 with immunomodulatory effects was expected to be useful for the development of new immunomodulatory agents. Simultaneously, the discovery of ADP80-2 further revealed the chemical composition of A. dahurica used as a traditional Chinese medicine and spice.

Structural elucidation of an immunological arabinan from the rhizomes of Ligusticum chuanxiong, a traditional Chinese medicine.

In the present study, an immunological arabinan, LCP70-2A, was isolated from Ligusticum chuanxiong for the first time. The absolute molecular weight of LCP70-2A was determined to be 6.46 × 104 g/mol using the HPSEC-MALLS-RID method. The absolute configuration of arabinose in LCP70-2A was determined to be L-configuration. Physicochemical characterization revealed that LCP70-2A was a homogeneous polysaccharide and had a backbone of (1 â†’ 5)-linked α-L-Araf with terminal α-L-arabinose residues at position O-2 and O-3. Molecular conformation analysis showed that LCP70-2A was a branching polysaccharide with a compact coil chain conformation in 0.1 M NaCl solution. In addition, in vitro cell assays showed that LCP70-2A can activate macrophages by enhancing the phagocytosis and potentiating the secretion of immunoregulatory factors including NO, TNF-α, IL-6, and IL-1ß. Furthermore, LCP70-2A was proved to promote the production of ROS and NO using the zebrafish model, suggesting that LCP70-2A can be further developed as a candidate supplement for immunological enhancement.

Isolation, structural elucidation, and immunoregulation properties of an arabinofuranan from the rinds of Garcinia mangostana.

In our search for bioactive polysaccharides as immunomodulatory agents, an arabinofuranan (GMP90-1) was purified and characterized from the rinds of Garcinia mangostana L. GMP90-1 (absolute molecular weight: 5.30 × 103 g/mol) was found to be composed of arabinose, galactose, and rhamnose. The backbone of GMP90-1 was determined as (1→5)-linked α-l-Araf, (1→2,3,5)-linked α-l-Araf, (1→3,5)-linked α-l-Araf, (1→6)-linked ß-d-Galp, and (1→2)-linked α-l-Rhap. Conformational analysis revealed GMP90-1 to exist as a rigid rod structure in sodium chloride solution. To explore its potential as immunomodulatory agents, an in vitro cell screening was performed and GMP90-1 was found to significantly enhance the phagocytic uptake of neutral red and improve the secreted level of nitric oxide (NO), interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α (TNF-α) of macrophages. Furthermore, the cellular immunomodulatory activities were confirmed by the in vivo zebrafish experiment, which suggested that GMP90-1 with immunomodulatory effects could be considered as a potential immunomodulatory for immune diseases.