Folic Acid-Conjugated Chitosan Nanoparticles Enhanced Protoporphyrin IX Accumulation in Colorectal Cancer Cells

Abstract

Folic acid can be covalently conjugated to chitosan molecules via its gamma-carboxyl moiety and thus retain a high affinity for colorectal cancer cells bearing folate receptor overexpression. Colorectal cancer is one of the leading causes of malignant death and often goes undetected with current colonoscopy practices. Improved methods of detecting dysplasia and tumors during colonoscopy will improve mortality. A folic acid conjugated chitosan nanoparticle as a suitable vehicle for carrying 5-aminolaevulinic acid (5-ALA) is developed to enhance the detection of colorectal cancer cells in vivo after a short-term uptake period. Chitosan can be successfully conjugated with folic acid to produce folic acid-chitosan conjugate, which is then loaded with 5-ALA to create nanoparticles (fCNA). The loading efficiency of 5-ALA in fCNA particles and the z-average diameter were in the range 35-40% and 100 nm, respectively. The zeta-potential for fCNA was 20 mV, enough to keep the nanoparticle stable without aggregation. The fCNA is then incubated with HT29 and Caco-2 colorectal cancer cell lines overexpressing folate receptor on the surface of the cell membrane to determine the rate of accumulation of protoporphyrin IX (PpIX). The results show that fCNA can be taken up more easily by HT29 and Caco-2 cell lines after short-term uptake period, most likely via receptor-mediated endocytosis, and the PpIX accumulates in cancer cells as a function of the folate receptor expression and the folic acid modification. Therefore, the folic acid-chitosan conjugate appears to be an ideal vector for colorectal-specific delivery of 5-ALA for fluorescent endoscopic detection.

Gemcitabine versus Modified Gemcitabine: A Review of Several Promising Chemical Modifications

“…Effective targeting with folate has been proven by using folate on the surface of many nanocarriers such as gold nanoparticles, liposomes or magnetic nanoparticles for the detection of cancer cells and the release of anticancer drugs. [57][58][59] All conjugates were able to release the drug in a pH-dependent manner with no role played by enzymes. The presence of a plasma enzyme does not accelerate the conversion of different compounds in dFdU which confirms previous studies showing that the protection of the amino group of gemcitabine prevents this.…”

Synthesis and characterisation of functionalized borosilicate nanoparticles for boron neutron capture therapy applications

“…The same authors ascribed the broad and complex band at 1696 cm -1 to the stretching of different -C=O groups, and the band at 1607 cm -1 to the bending of -NH groups. In contrast, Yang et al [23] assigned both the band at 1607 cm -1 and the band at 1449 cm -1 to the stretching of aromatic C=C bonds. Vora et al [24] assigned the bands between 2860 and 2960 cm -1 to the symmetric and antisymmetric stretching of C-H bonds.…”

5-aminolevulinic acid-incorporated nanoparticles of methoxy poly(ethylene glycol)-chitosan copolymer for photodynamic therapy

“…35 Furthermore, other researchers have reported that chitosan hydrogels or folic acid-conjugated chitosan can be an efficient carrier for delivering 5-ALA to tumor cells. 37,38 Yang et al also observed time-dependent accumulation of pPIX in the tumor cells and pPIX accumulation was highest at 112 hours of incubation. Our results revealed that PEG-Chito-5-ALA nanoparticles also induce enhanced phototoxicity against CT26 colon cancer cells and then accelerate the apoptosis or necrosis of the cells, as shown in Figure 8.…”

“…1,2,6,10 To overcome these problems, chemical modification of 5-ALA, 5-ALA-incorporated nanocolloid, patch-based delivery system, or liposomal carriers were tried, in order to improve delivery of 5-ALA. 14,15,18,19 Chitosan has been extensively investigated as a geneor drug-delivery carrier. [25][26][27][28][33][34][35] In particular, chitosan is known to enhance mucosal transport or delivery of bioactive agents. 34,35 Therefore, chitosan is regarded as a promising vehicle for transmucosal or oral delivery of drugs.…”