<p>Antitumor effect of hyaluronic-acid-modified chitosan nanoparticles loaded with siRNA for targeted therapy for non-small cell lung cancer</p>

Abstract

Purpose: Nanoparticle (NP)-mediated targeted delivery of therapeutic genes or siRNAs to tumors has potential advantages. In this study, hyaluronic acid (HA)-modified chitosan nanoparticles (CS NPs-HA) loaded with cyanine 3 (Cy3)-labeled siRNA (sCS NPs-HA) were prepared and characterized. Methods: Human non-small cell lung cancer (NSCLC) A549 cells expressing receptor CD44 and tumor-bearing mice were used to evaluate the cytotoxic and antitumor effects of sCS NPs-HA in vitro and in vivo. Results: The results showed that noncytotoxic CS NPs-HA of small size (100–200 nm) effectively delivered the Cy3-labeled siRNA to A549 cells via receptor CD44 and inhibited cell proliferation by downregulating the target gene BCL2 . In vivo experiment results revealed that sCS NPs-HA directly delivered greater amounts of Cy3-labeled siRNA to the tumor sites, resulting in the inhibition of tumor growth by downregulating BCL2 , as compared to unmodified NPs loaded with siRNA (sCS NPs) and to naked Cy3-labeled siRNA. Conclusion: The HA-modified NPs based on chitosan could serve as a promising carrier for siRNA delivery and targeted therapy for NSCLC expressing CD44.

Electrospun Fibres with Hyaluronic Acid-Chitosan Nanoparticles Produced by a Portable Device

“…Nanoparticles are particularly interesting for biomedical applications, mainly because they offer high encapsulation efficiency, are able to penetrate tissues, usually have a slow degradation rate, have a small mean size, and effective targetability [ 36 ]. HA-CS nanoparticles have been used for a number of clinical applications, including protein and drug delivery [ 26 ], contrast agents and macromolecule carriers [ 27 , 37 , 38 ]. These nanoparticles are particularly useful for tissue engineering applications, as they interact well with cell surfaces and offer prolonged residence time at the target site [ 35 ].…”

“…Nanoparticles offer high encapsulation efficiency and penetration ability, slow degradation rate, small mean size (10–1000 nm) and effective targetability [ 36 ]; characteristics that are particularly useful for biomedical applications. Clinical applications of HA-CS NPs include non-viral vectors for gene delivery [ 26 ], protein or drug delivery [ 33 ], tumour-targeted magnetic resonance imaging (MRI) contrast agents and macromolecule micro/nanocarriers [ 27 ] with controlled release, including heparin [ 35 ], interleukin (IL)-1β [ 37 ], DNA and RNA [ 38 ].…”

Chitosan Nanoparticles-Insight into Properties, Functionalization and Applications in Drug Delivery and Theranostics

“…Hyaluronic acid chitosan NPs encapsulated with cyanine3 labelled siRNA were conjugated with CD44 receptors for non-small cell lung cancer. The result showed that these NPs effectively delivered the siRNA to the target cells via CD44 receptor and inhibited cell proliferation by down regulating B-cell lymphoma 2 gene [ 107 ].…”

Extracellular Matrix Mimics Using Hyaluronan-Based Biomaterials

“…The chemical composition of HA with available reactive groups (e.g., carboxylic acids) allows the exploitation of electrostatic or covalent interactions with other materials. For instance, the negative charge of HA (-COO -) allows it to participate in electrostatic binding with the positively Trends in Biotechnology charged chitosan, used for the targeted delivery of siRNA or the drug everolimus to lung cancer cells [34]. To promote the interaction between HA and the negative charged SiO 2 or Au particles, these cores are usually amine-functionalized (-NH 2 ), or layer-by-layer (LbL) assembly is applied to revert the surface charge of the core particles [35].…”