Abstract
BackgroundActive targeting endocytosis mediated by the specific interaction between folic acid and its receptor has been a hotspot in biological therapy of many human cancers. Various studies have demonstrated that folate and its conjugates could facilitate the chemotherapeutic drug delivery into folate receptor (FR)-positive tumor cells in vitro and in vivo. In order to utilize FA-FR binding specificity to achieve targeted delivery of drugs into tumor cells, we prepared Gefitinib loaded folate decorated bovine serum albumin conjugated carboxymethyl-β-cyclodextrin nanoparticles for enhancing drug delivery in cancer cells. On this context, the aim of our study was to develop a novel nano-delivery system for promoting tumor-targeting drug delivery in folate receptor-positive Hela cells.ResultsWe prepared folic acid (FA)-decorated bovine serum albumin (BSA) conjugated carboxymethyl-β-cyclodextrin (CM-β-CD) nanoparticles (FA-BSA-CM-β-CD NPs) capable of entrapping a hydrophobic Gefitinib. It was observed that nanoparticles are monodisperse and spherical nanospheres with an average diameter of 90.2 nm and negative surface charge of −18.6 mV. FA-BSA-CM-β-CD NPs could greatly facilitate Gefitinib uptake and enhance the toxicity to folate receptor-positive Hela cells. Under the reaction between FA and FR, Gefitinib loaded FA-BSA-CM-β-CD NPs induced apoptosis of Hela cells through elevating the expression of caspase-3 and inhibited autophagy through decreasing the expressing of LC3. It also confirmed that clathrin-mediated endocytosis and macropinocytosis exerted great influence on the internalization of both NPs.ConclusionsThese results demonstrated that FA may be an effective targeting molecule and FA-BSA-CM-β-CD NPs provided a new strategy for the treatment of human cancer cells which over-expressed folate receptors.
Highlights
Active targeting endocytosis mediated by the specific interaction between folic acid and its receptor has been a hotspot in biological therapy of many human cancers
We found that folic acid (FA)-Bovine serum albumin (BSA)-CM-β-CD NPs greatly facilitated Gefitinib uptake and enhanced the toxic effect in folate receptor-positive Hela cells
Our results demonstrated that FA-BSA-CM-β-CD NPs might be a higher efficiency drug delivery system than the conventional delivery system for the targeting therapy of folate receptor (FR) positive human cancers
Summary
Active targeting endocytosis mediated by the specific interaction between folic acid and its receptor has been a hotspot in biological therapy of many human cancers. In order to utilize FA-FR binding specificity to achieve targeted delivery of drugs into tumor cells, we prepared Gefitinib loaded folate decorated bovine serum albumin conjugated carboxymethyl-β-cyclodextrin nanoparticles for enhancing drug delivery in cancer cells. On this context, the aim of our study was to develop a novel nano-delivery system for promoting tumor-targeting drug delivery in folate receptor-positive Hela cells. Cyclodextrins (CD), a family of carbohydrate polymers which are produced from starch by enzymatic conversion and commonly used in food, pharmaceutical, drug delivery, and chemical industries, as well as agriculture and environmental engineering, is cyclic oligosaccharide with cone barrel structure composed of seven glucopyranose units with cylindrical cavity [14,15,16]. Bovine serum albumin (BSA), a carrier protein, plays an important role in drug storage and transport, for its superior biocompatibility it has been widely used in biomedical research, such as Nano carrier, nanoparticle surface engineering and temples for preparation of nanoparticles [22,23,24,25]
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