Synergistically enhanced selective intracellular uptake of anticancer drug carrier comprising folic acid-conjugated hydrogels containing magnetite nanoparticles

Abstract

Targeted drug delivery has long been extensively researched since drug delivery and release at the diseased site with minimum dosage realizes the effective therapy without adverse side effects. In this work, to achieve enhanced intracellular uptake of anticancer drug carriers for efficient chemo-therapy, we have designed targeted multifunctional anticancer drug carrier hydrogels. Temperature-responsive poly(N-isopropylacrylamide) (PNIPAm) hydrogel core containing superparamagnetic magnetite nanoparticles (MNP) were prepared using precipitation polymerization, and further polymerized with amine-functionalized copolymer shell to facilitate the conjugation of targeting ligand. Then, folic acid, specific targeting ligand for cervical cancer cell line (HeLa), was conjugated on the hydrogel surface, yielding the ligand conjugated hybrid hydrogels. We revealed that enhanced intracellular uptake by HeLa cells in vitro was enabled by both magnetic attraction and receptor-mediated endocytosis, which were contributed by MNP and folic acid, respectively. Furthermore, site-specific uptake of the developed carrier was confirmed by incubating with several other cell lines. Based on synergistically enhanced intracellular uptake, efficient cytotoxicity and apoptotic activity of HeLa cells incubated with anticancer drug loaded hybrid hydrogels were successfully achieved. The developed dual-targeted hybrid hydrogels are expected to provide a platform for the next generation intelligent drug delivery systems.

Colorectal cancer-targeted delivery of oxaliplatin via folic acid-grafted solid lipid nanoparticles: preparation, optimization, and in vitro evaluation

“…OPloaded folate coupled SLNs exhibited significantly higher cytotoxicity as compared to plain drug solution. This phenomenon may be attributed to the conjugation of SLN with FA, which enhanced cellular uptake, via receptor mediated internalization by the cells [34]. The folate conjugation on SLNs periphery might have contributed to lower IC 50 value.…”

Effect of inhibitors of endocytosis and NF-kB signal pathway on folate-conjugated nanoparticle endocytosis by rat Kupffer cells

“…FA was selected as the targeting ligand since it is one of the bestcharacterized ligands to be exploited for targeting cancer cells. 19 Many drug delivery vehicles, such as liposomes, proteins, polymeric NPs, linear polymers, and dendrimers, have been modified with FA to increase their cellular uptake in FR-overexpressing tumor cells. [16][17][18] Epirubicin (EPI)-loaded FA-conjugated pullulan acetate (FPA/EPI) NPs and FAconjugated chitosan-coated poly(d,l-lactide-co-glycolide) NPs might have potential applications in cervical cancer therapy.…”

“…20,21 FA was conjugated to pullulan acetate to form the conjugated ligand and thereafter the pullulan acetate nanocarrier. Chen et al 18 and Kim et al 19 revealed that enhanced intracellular uptake by HeLa cells (FR-positive) in vitro was enabled by receptor-mediated endocytosis and that FA contributed to this effect. Our previous in vitro and in vivo results 20,21 suggested that FPA/EPI NPs showed promise in treating cervical carcinoma because of its high stability, low toxicity, and slow-release pharmacokinetic characteristics.…”

rGO nanomaterial-mediated cancer targeting and photothermal therapy in a microfluidic co-culture platform

“…2c). While the spectrum of rGO-PEG did not show any absorption peak, rGO-PEG-FA showed the additional peak at 280 nm, which was distinctive in FA [63,64]. This result supported that FA molecules were grafted on rGO surface with PEG.…”