Asialoglycoprotein receptor mediated hepatocyte targeting - strategies and applications.

Patients treated with conventional cancer chemotherapy suffer from side effects of the drugs due to non-selective action of chemotherapeutic drugs to normal cells. Active targeting nanoparticles that are conjugated to targeting ligands on the surface of nanoparticles play an important role in improving drug selectivity to the cancer cell. Several chemotherapeutic drugs and traditional/herbal medicines reported for anticancer activities have been investigated for their selective delivery to cancer cells by active targeting nanoparticles. This systematic review summarizes reports on this application. Literature search was conducted through PubMed database search up to March 2017 using the terms nanoparticle, chemotherapy, traditional medicine, herbal medicine, natural medicine, natural compound, cancer treatment, and active targeting. Out of 695 published articles, 61 articles were included in the analysis based on the predefined inclusion and exclusion criteria. The targeting ligands included proteins/peptides, hyaluronic acid, folic acid, antibodies/antibody fragments, aptamer, and carbohydrates/polysaccharides. In vitro and in vivo studies suggest that active targeting nanoparticles increase selectivity in cellular uptake and/or cytotoxicity over the conventional chemotherapeutic drugs and non-targeted nanoparticle platform, particularly enhancement of drug efficacy and safety. However, clinical studies are required to confirm these findings.

/pdf/application-of-active-targeting-nanoparticle-delivery-system-1idyav39pw.pdf

Application of active targeting nanoparticle delivery system for chemotherapeutic drugs and traditional/herbal medicines in cancer therapy: a systematic review.

Polysaccharide based nanogels in the drug delivery system: Application as the carrier of pharmaceutical agents

Nanoparticulate drug/gene carriers have gained much attention in the past decades because of their versatile and tunable properties. However, efficacy of the therapeutic agents can be further enhanced using naturally occurring materials-based nanoparticles. Polysaccharides are an emerging class of biopolymers; therefore, they are generally considered to be safe, non-toxic, biocompatible and biodegradable. Considering that the target of nanoparticle-based therapeutic strategies is localization of biomedical agents in subcellular compartments, a detailed understanding of the cellular mechanism involved in the uptake of polysaccharide-based nanoparticles is essential for safe and efficient therapeutic applications. Uptake of the nanoparticles by the cellular systems occurs with a process known as endocytosis and is influenced by the physicochemical characteristics of nanoparticles such as size, shape and surface chemistry as well as the employed experimental conditions. In this study, we highlight the main endocytosis mechanisms responsible for the cellular uptake of polysaccharide nanoparticles containing drug/gene.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/jcmm.13110

Overviews on the cellular uptake mechanism of polysaccharide colloidal nanoparticles.

Pectin, a complex class of plant polysaccharides, is composed of a galacturonan backbone and neutral sugar side chains. Natural pectin is reported to prevent colon cancer as a dietary fiber (DF). To enhance its bioavailability and bioactivity, pectin was modified into bioavailable modified pectin fragments (MPs) with low molecular mass. Also, MPs had low degrees of esterification (DE) which is reported to inhibit tumor growth, induce apoptosis, suppress metastasis, and modulate immunological responses. Antitumor activity of MPs chiefly arises from intervention in ligand recognition by galectin-3 (Gal-3). In addition, pectin is a suitable vehicle for anti-cancer drug delivery systems, due to its abundant modifiable functional groups and special physicochemical properties. Here, we summarize the structural features, bio-absorption and antitumor mechanisms and the structure-activity relationship of MPs. We also offer prospects and challenges for developing pectin into nutraceuticals or drugs.

Pectin in cancer therapy: A review

The fabrication and evaluation of a natural pectin-based drug delivery system are reported in this study. The drug delivery system displays specific active targeting ability to hepatocellular carcinoma due to the presence of excess galactose residues in the polymer structure as the natural targeting ligands. The system was prepared under very mild conditions in an aqueous medium containing Ca(2+) and CO3(2-) ions, generating uniform pectin-based nanoparticles with an average diameter of 300 nm, and the drug-loading content of anticancer drug 5-fluorouracil (5-FU) is around 24.8%. Cytotoxicity study of the 5-FU-loaded nanoparticles (5-FU-NPs) in HepG2 and A549 cell lines demonstrated their greater potency in killing cancer cells with overexpressed asialoglycoprotein receptor (ASGPR) on the cell surface, compared to that of the free drug. Pharmacokinetics study using Sprague-Dawley (SD) rats further confirmed that the drug-loaded nanoparticles showed a much longer half-life in the circulation fluids than the free drug. Tissue distribution was investigated on Kunming mice, and the results also demonstrated that the 5-FU-NPs has a long circulation effect. Taken together, the pectin-based drug delivery systems exhibit size-induced prolonged circulation as well as ASGP receptor-mediated targeting ability to cancer cell lines; therefore, it is a promising platform for the treatment of hepatocellular carcinoma.

In Vitro and in Vivo Evaluation of Pectin-Based Nanoparticles for Hepatocellular Carcinoma Drug Chemotherapy

The invention relates to a preparation method of a dimensionality-stable regenerated cellulose fiber. The preparation method comprises the following steps: carrying out dipping, squeezing, crushing, ageing, yellowing, continuous dissolving, filtering, and deaeration operations on a cellulose raw material to prepare a spinning viscose glue; and spinning to prepare the dimensionality-stable regenerated cellulose fiber, wherein a mixture comprising one or more of a denaturant and a crosslinking agent is added in the continuous dissolving step of the spinning viscose glue operation or before the spinning step. The dimensionality, the dry strength, the wet strength and the dry extension of the dimensionality-stable regenerated cellulose fiber are 1.4-1.72dtex, 1.6-3.0CN/dtex, 1.2-2.8CN/dtex and 10-20% respectively. The dimensionality-stable regenerated cellulose fiber prepared by adopting the method of the invention overcomes disadvantages of low fabric preparation rate and bad dimensional stability caused by the overhigh hygroscopic expansion rate and large wet tensile elongation of common viscose fibers, and has the advantages of stable transverse section and vertical dimensionality, and strong weaving strength.

Dimensionality-stable regenerated cellulose fiber and preparation method thereof

Characterization and fabrication of multi-layer films based on polysaccharide and cellulose

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In Vitro and in Vivo Evaluation of Pectin-Based Nanoparticles for Hepatocellular Carcinoma Drug Chemotherapy

Dimensionality-stable regenerated cellulose fiber and preparation method thereof

Characterization and fabrication of multi-layer films based on polysaccharide and cellulose