Abstract
In this study, fluorescein-labelled wheat germ agglutinin (fWGA)-conjugated disulfide cross-linked sodium alginate nanoparticles were developed to specifically target docetaxel (DTX) to colon cancer cells. Different amounts of 3-mercaptopropionic acid (MPA) were covalently attached to sodium alginate to form thiolated sodium alginate (MPA1–5). These polymers were then self-assembled and air-oxidised to form disulfide cross-linked nanoparticles (MP1–5) under sonication. DTX was successfully loaded into the resulting MP1–5 to form DTX-loaded nanoparticles (DMP1–5). DMP2 had the highest loading efficiency (17.8%), thus was chosen for fWGA surface conjugation to form fWGA-conjugated nanoparticles (fDMP2) with a conjugation efficiency of 14.1%. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) analyses showed spherical nanoparticles, and an in vitro drug release study recorded a cumulative drug release of 48.6%. Dynamic light scattering (DLS) analysis revealed a mean diameter (MD) of 289 nm with a polydispersity index (PDI) of 0.3 and a zeta potential of −2.2 mV for fDMP2. HT-29 human colon cancer cells treated with fDMP2 showed lower viability than that of L929 mouse fibroblast cells. These results indicate that fDMP2 was efficiently taken up by HT-29 cells (29.9%). Fluorescence and confocal imaging analyses also showed possible internalisation of nanoparticles by HT-29 cells. In conclusion, fDMP2 shows promise as a DTX carrier for colon cancer drug delivery.
Highlights
Colon cancer is one of the main causes of death in Malaysia and in most countries around the world [1]
The micro bicinchoninic acid (BCA) protein assay kit was acquired from Thermo Fisher (San Diego, CA, USA). fluorescein-labelled wheat germ agglutinin (fWGA) was purchased from Vector Laboratories (Burlingame, CA, USA). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Tween 20 were obtained from Sigma Aldrich
HT-29 and L929 cells were cultured in Roswell Park Memorial Institute 1640 (RPMI) and Dulbecco’s modified eagle medium (DMEM) (10% foetal bovine serum (FBS); 1% penicillin-streptomycin), respectively [48]
Summary
Colon cancer is one of the main causes of death in Malaysia and in most countries around the world [1]. Nanocarriers derived from disulfide bond-containing polymers are stable in normal cells, in which the drug will not leak from the nanocarriers along the route to the targeted site, reducing the toxicity and side effects of drug to the normal cells. Disulfide bonds are readily reduced or cleaved in a reductive environment (low redox potential), thereby allowing the drug to be released in the colon [21,22] This promotes the systemic delivery of drugs to the targeted part of the human body. The tagging of targeting ligand, WGA with carboxyl groups at the backbone of sodium alginate bind to the N-acetylglucosamine and sialic acid on the membrane of the cancer cells This targeted drug delivery system provides prolonged circulation time, enhanced cellular-uptake, higher drug accumulation at tumour site, avoiding lysosomal degradation and specific release of drug at targeted site. The stability, pH sensitivity, reduction response, in vitro release of DTX, cell viability, and uptake of nanoparticles by cells were investigated
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