Hyaluronic acid-coated chitosan nanoparticles induce ROS-mediated tumor cell apoptosis and enhance antitumor efficiency by targeted drug delivery via CD44

Abstract

BackgroundA targeted drug nanoparticle (NP) delivery system has shown potential as a possible cancer treatment. Given its merits, such as its selective distribution at tumor sites and its controllable drug release, drug-loaded NPs can be effectively delivered to selected organs and targeted cells, thus enhancing its antitumor efficiency and reducing its toxicity.MethodsWe reported that hyaluronic acid (HA)-coated chitosan NPs promoted the drug delivery of 5-fluorouracil (5-Fu) into tumor cells that highly expressed CD44.ResultsOur new findings suggested that HA-coated chitosan NPs enhanced drug accumulation by effectively transporting NPs into CD44-overexpressed tumor cells, and they also resulted in mitochondrial damage induced by the production of reactive oxygen species (ROS). Compared to free drug and uncoated NPs, HA-coated chitosan NPs exhibited stronger inhibition rates and induced obvious apoptosis in CD44-overexpressed A549 cells.ConclusionsBiocompatible and biodegradable HA-coated chitosan NPs were developed to encapsulate a chemotherapeutic drug (5-Fu) to enhance drug accumulation in tumor cells and to improve the agent’s antitumor efficiency by offering targeted drug delivery via CD44.

Folic Acid Conjugated PEG-PCL-PEG Triblock Copolymer Nanoparticles for Enhanced Delivery of 5-Fluorouracil to HT29 Colon Cancer Cells

“…This nding can be justi ed by considering their different cellular uptake pathways. It is well known that 5-FU as hydrophilic drug has a poor penetration into cell through diffusion and is highly prone to washed out while NPs could internalize into cell via endocytosis [23,[37][38][39][40]. Endocytosis of NPs has been shown as an approach to bypass drug e ux pumps and subsequently reverse multidrug resistance [41][42][43].…”

Polysaccharide Based Nanoparticles

“…Ho et al., developed antibody‐modified CS nanoparticles for the targeted delivery of siRNA across the blood‐brain barrier as a strategy for inhibiting HIV replication in astrocytes. Shi and co‐workers prepared HA coated CS nanoparticles to encapsulate 5‐fluorouracil using ion gelation method. These nanoparticles showed a sustained drug release behaviour.…”

Hyaluronic Acid in the 3^rd Millennium

“…Moreover, HA-poly(N-isopropylacrylamide) conjugate appear a promising candidate to treat osteoarthritis: once injected subcutaneously or intra-articularly, it spontaneously forms biocompatible nanoparticles able to control inflammation with a long-lasting action [192]. Finally, other HA surface-modified nanoparticles have been investigated for cancer targeted therapies [196][197][198].…”

“…Many researches have shown that HA can act as drug carrier and targeting agent at the same time, under the form of polymer-antitumoral conjugates, or delivery systems encapsulating anticancer drugs [179]. Additionally, hyaluronan can be employed to design surface-modified nanoparticles [196][197][198] or liposomes [184][185][186][187][188]. After CD44 receptor-mediated cell internalization, all these HA derivatives are hydrolyzed by intracellular enzymes and, therefore, drugs are released inside the cancer target cells [179].…”

“…For example, it has been shown that HA-modified polycaprolactone nanoparticles encapsulating naringenin enhance drug uptake by cancer cells in vitro, and inhibit tumor growth in rat with urethane-induced lung cancer [198]. Additionally, HA-coated chitosan nanoparticles have been found to promote 5-fluorouracil delivery into tumor cells that overexpress CD44 receptor [196]. Further studies have displayed that a novel unsaturated derivative of HA [209] and different types of HA-paclitaxel conjugates [179,183] have a great potential as anticancer therapies.…”