Versatile Types of Polysaccharide-Based Drug Delivery Systems: From Strategic Design to Cancer Therapy.

Chemotherapy is still the most direct and effective means of cancer therapy nowadays. The proposal of drug delivery systems (DDSs) has effectively improved many shortcomings of traditional chemotherapy drugs. The technical support of DDSs lies in their excellent material properties. Polysaccharides include a series of natural polymers, such as chitosan, hyaluronic acid, and alginic acid. These polysaccharides have good biocompatibility and degradability, and they are easily chemical modified. Therefore, polysaccharides are ideal candidate materials to construct DDSs, and their clinical application prospects have been favored by researchers. On the basis of versatile types of polysaccharides, this review elaborates their applications from strategic design to cancer therapy. The construction and modification methods of polysaccharide-based DDSs are specifically explained, and the latest research progress of polysaccharide-based DDSs in cancer therapy are also summarized. The purpose of this review is to provide a reference for the design and preparation of polysaccharide-based DDSs with excellent performance.

SPHK1 inhibitor suppresses cell proliferation and invasion associated with the inhibition of NF-κB pathway in hepatocellular carcinoma.

Sphingosine kinase 1 (SphK1) is an oncogenic enzyme promoting transformation, proliferation, and angiogenesis of a number of human tumors. However, its effect on hepatocellular carcinoma (HCC) behavior has not been fully clarified. The purpose of this study was to determine the correlation between HCC and SphK1, and to evaluate the effect of SphK1 inhibitor N,N-dimethylsphingosine (DMS) in HCC. The expression of SphK1 was measured in tissue samples from 76 HCC and paired adjacent noncancerous liver tissues (NT) by immunohistochemistry, quantitative real-time PCR, and Western blotting analysis. The effect of DMS was tested on HCC cells by evaluating cell viability in vitro. Transwell cell migration and invasion assay were carried out for functional analysis. Furthermore, Western blotting analysis was performed to examine the impact of DMS on the PI3K/Akt/NF-kB signaling. High expression of Sphk1 was observed in 84.21% (64/76) of the HCC versus 15.79% (12/76) of the adjacent non-tumorous liver tissues; the difference of Sphk1 expression between HCC and the adjacent non-tumorous liver tissues was statistically significant (P < 0.001). The results were confirmed by Western blot analyses and quantitative real-time PCR. DMS inhibited the proliferation of SK-Hep1 and MHCCLM3 cells which have a relatively high level of SphK1 in a time- and concentration-dependent manner, and the invasion and migration of SK-Hep1 cells were distinctly suppressed after undergoing treatment with DMS. Furthermore, DMS markedly suppressed the expression of phosphorylations of Akt and NF-κB in HCC cells. Our data suggest that the pathogenesis of human HCC maybe mediated by Sphk1, and the specific Sphk1 inhibitor DMS can play a therapeutic role in the treatment of HCC and thus, Sphk1 could represent selective targets for the molecularly targeted treatments of HCC.

A chitosan derivative-crosslinked hydrogel with controllable release of polydeoxyribonucleotides for wound treatment.

Nucleic acid-based agents have advantages in therapeutic efficacy and biological safety. However, due to its facile degradability, it lacks an effective route of administration in wound treatment. Designing smart hydrogels for the spatiotemporally controllable delivery of nucleic acids is of great significance for clinical applications. Here, a near-infrared (NIR)-responsive nanocomposite hydrogel was prepared using methyl methacrylate (GMA)-modified chitosan as the macromolecular cross-linker, N-isopropylacrylamide (NIPAAm) as the backbone, and molybdenum disulfide nanosheets (MoS2 NSs) as the nanocomponents. The polydeoxyribonucleotide (PDRN), a nucleic acid-based agent that promotes tissue regeneration, was loaded and delivered. The photothermal conversion capability of MoS2 NSs enables customized care of PDRNs and antibacterial enhancement. In a full-thickness skin defect model, high-quality wound healing effects were demonstrated under the action of nanocomposite hydrogels. The proposed nanocomposite hydrogel provides a new reference for local delivery of nucleic acid-based agents.

Pathology and ultrasound findings in diffuse sclerosing thyroid papillary carcinoma.

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The Intracellular and Extracellular Microenvironment of Tumor Site: The Trigger of Stimuli-Responsive Drug Delivery Systems.

The tumor microenvironment (TME), including intracellular and extracellular microenvironment, contains many biochemical indicators (such as acidity/alkalinity, oxygen content, and enzymatic activity) that are different from the normal physiological environment. These abnormal biochemical indicators can accelerate the heterogeneity of tumors, but on the other hand, they also provide opportunities for the design of intelligent drug delivery systems (DDSs). The TME-responsive DDSs have shown great potential in reducing the side effects of chemotherapy and improving the curative effect of tumors. In this review, the abnormal biochemical indicators of TME are introduced in detail from both the extracellular and intracellular aspects. In view of the various physiological barriers encountered during drug delivery, the strategy of constructing TME-responsive DDSs is discussed. By summarizing the typical research progress, the authors prospect the development of TME-responsive DDS in the future.

PAMAM-Functionalized Cellulose Nanocrystals with Needle-Like Morphology for Effective Cancer Treatment.

Gene therapy is used to correct or compensate for diseases caused by gene defects and abnormalities. Improving the transfection efficiency and reducing the toxicity of gene carriers are the keys to gene therapy. Similar to a typical cationic gene carrier-polyethylenimine (PEI, 25 kDa)-the polyamidoamine (PAMAM) dendrimer also has a large number of amino groups. These amino groups can be complexed with nucleic acids after protonation under physiological conditions. However, the concentrated positive charge can cause undesirable cytotoxicity. Cellulose nanocrystals (CNCs) have good biocompatibility and unique needle-like morphology, and have been proven to be efficiently taken up by cells. In this article, three-dimensional spherical PMAMA dendrimers are conjugated onto the surface of CNCs to obtain a kind of needle-like cationic carrier (CNC-PAMAM). PAMAM dendrimers act as anchors to bind the plasmid DNAs (pDNA) to the surface of the CNC. The prepared CNC-based carrier showed high transfection efficiency and low toxicity. The CNC-PAMAM can effectively deliver the suicide gene to the tumor site, enabling the suicide gene/prodrug system (cytosine deaminase/5-fluorocytosine (CD/5-FC)) to play an effective anti-tumor role in vivo. This research demonstrates that the functionalization of CNCs with PAMAM dendrimers is an effective method for developing novel gene delivery systems.

Alginate/chitosan-based hydrogel loaded with gene vectors to deliver polydeoxyribonucleotide for effective wound healing.

Timely and effective wound treatment is of great significance in acute bleeding caused by accidents and chronic wounds such as diabetic foot ulcers, venous leg ulcers, pressure sores. A hydrogel as wound dressing can provide a suitable microenvironment for wound healing and prevent bacteria and dust from reaching the wound. The loading of therapeutic factors in the hydrogel has been proved to accelerate wound healing. Polydeoxyribonucleotide (PDRN), as a series of nucleic acid fragments extracted from salmon, has the functions of improving angiogenesis, promoting cell activity, increasing collagen synthesis, and developing the anti-inflammatory response. These effects have positive implications for wound healing. But naked PDRN is difficult to take up by cells. Inspired by gene vectors, we prepared a PDRN-loaded CaCO3 nanoparticle (PCNP) to improve the delivery efficiency of PDRN. PCNPs were encapsulated in an alginate/chitosan-based hydrogel (Gel@PCNPs). The prepared hydrogel has plasticity and is suitable for various irregular wounds. The released gene carrier, PCNP, can be effectively taken up by skin fibroblasts. Under the action of PDRN, the wound healing rate has been confirmed to be significantly accelerated. We believe that this polysaccharide-based hydrogel loaded with PDRN vectors is a promising wound dressing.