Anticancer Activity of Released Doxorubicin from a Folate-Mediated Polyelectrolyte Complex

Abstract

Folic acid (FA) was selected to link with macromolecules for the selective and specific delivery of doxorubicin (DOX) to folate receptor (FR)-positive tumor cells, because of the high binding affinity of FA to the tumor-associated FR. We synthesized folate-mediated chondroitin sulfate (FA-PEG-ChS) for tumor cell targeting and non-folate-mediated naproxen-linked chondroitin sulfate (Nap-PEG-ChS) for comparison. Both the aforementioned polymers contain a PEG1000 spacer. We encapsulated an anticancer agent, DOX, during the formation of complexes with chitosan. Polyelectrolyte complexes (PEC) grafted with a fluorescent dye (FITC) served as a platform for online imaging cellular internalization. FR-positive KB and FR-deficient A549 cancer cells were tested. The concentration to kill 50% of the cells (IC(50)) of DOX-loaded FA-complex was 1.53 μg/ml, in comparison to 0.91 μg/ml of free DOX. The overlaid fluorescent images of DOX and FITC on confocal laser scanning microscopy demonstrated the co-internalization of DOX and the complex nanoparticles into the cytoplasm of KB cells followed by a gradual release of DOX.

Biocompatibility and Stability of Polysaccharide Polyelectrolyte Complexes Aimed at Respiratory Delivery

“…As a matter of fact, CS/CHS nanoparticles were reported in several works with varied applications, mainly including tissue engineering [12,13,14,15,16]. Other applications like cancer therapy [17,18], anticoagulant activity [10], anti-leishmanial activity [19] and cell transfection [20] were also referred. One sole research group reported their use in mucosal protein delivery [11,21], focusing an application in oral administration and using fluorescein isothiocyanate bovine serum albumin (FITC-BSA) as model protein.…”

Bioresorbable polyelectrolytes for smuggling drugs into cells

“…The folate receptor has been broadly utilized in targeted drug delivery, especially to target cancer cells, as expression of the folate receptor is selectively upregulated in tumor sites of various organs such as colon, lung, prostate, ovaries, mammary glands, and brain (Morris and Sharma 2011). Folic acid (FA), or folate, specifically binds to the folate receptor, and therefore folate has been conjugated to many polyelectrolytes (Jeong et al 2005, Kim et al 2007, Chiu et al 2011, Nukolova et al 2011, Chiang et al 2013, Mandal et al 2011 for active targeted drug delivery to cancer cells. For example, Zhou et al fabricated PEMs composed of chitosan and alginate assembled by the LbL method on the surface of the BSA-stabilized biocompatible poly(lactide-co-glycolide) nanoparticles.…”

Chitosan-Grafted Copolymers and Chitosan-Ligand Conjugates as Matrices for Pulmonary Drug Delivery

“…These systems have been developed with a view to achieve targeting effect in the delivery of cytostatic drugs to tumor cells, genetic material, or antiarthritis therapies and also for diagnostic and imaging purposes. To this end, the majority of in vitro studies have been conducted in various types of cell lines well known to overexpress the human folate receptors (FRa and FLRb), such as HeLa [145], HT29 [143], Caco-2 [143], B16F1 [150], KB [151,152], HepG-2 [153], and SKOV3 [141,154] cells.…”