Hyaluronic acid-tagged silica nanoparticles in colon cancer therapy: therapeutic efficacy evaluation

Abstract

Colon cancer is one of the leading causes of cancer-related death worldwide, and the therapeutic application of 5-fluorouracil (5-FU) is limited due to its nonspecificity, low bioavailability, and overdose. The present study is an attempt to improve the chemotherapeutic efficacy of 5-FU in colon cancers. Therefore, we have prepared 5-FU-loaded hyaluronic acid (HA)-conjugated silica nanoparticles (SiNPs) to target to colon cancer cells. In this study, we have showed the specific binding and intracellular accumulation of targeted nanoparticles based on HA surface modifications in colon carcinoma cells. The particles had spherical shapes with sizes of approximately 130 nm. HA-conjugated nanoparticles showed a sustained release pattern for 5-FU and continuously released for 120 hours. We have further investigated the cytotoxicity potential of targeted and nontargeted nanoparticles in colo-205 cancer cells. IC50 value of 5-FU/hyaluronic acid-conjugated silica nanoparticles (HSNP) was 0.65 µg/mL compared with ~2.8 µg/mL for 5-FU/SNP after 24 hours of incubation. The result clearly showed that HA-conjugated NP was more effective in inducing apoptosis in cancer cells than nontargeted NP. The 5-FU/HSNP showed ~45% of cell apoptosis (early and late apoptosis stage) compared with only 20% for 5-FU/silica nanoparticles (SNP)-treated group. The HA-conjugated nanoparticles provide the possibility of efficient drug transport into tumors that could effectively reduce the side effects in the normal tissues. 5-FU/HSNP was highly efficient in suppressing the tumor growth in xenograft tumor model. The proportion of Ki67 in 5-FU/HSNP-treated group was significantly lower than that of either free drug or nontargeted SiNPs. Altogether, we have showed that conjugation of HA to SiNPs could result in enhanced uptake of 5-FU through CD44-mediated endocytosis uptake and could result in significant antitumor efficacy. Thus, 5-FU/HSNP could be a promising drug delivery system for colon cancer therapy.

Enhancement of 5-FU sensitivity by the proapoptotic rpL3 gene in p53 null colon cancer cells through combined polymer nanoparticles

“…HA is reported to possess strong affinity toward the CD44 overexpressing cancer cells [ 38 ]. HA is nonantigenic and biocompatible and shows high affinity toward the receptors [ 39 ]. In addition, CD44 receptors are overexpressed in different human cancer cells and their density increases with the stages of cancers [ 38 ].…”

A Comprehensive Study on Folate-Targeted Mesoporous Silica Nanoparticles Loaded with 5-Fluorouracil for the Enhanced Treatment of Gynecological Cancers

“…The distinctive different release behaviors of MSN-NH2-FU and MSN-NH2-FU-FA indicated that drugs encapsulated in FA-conjugated nanoparticles could release 5-FU as a sustained type of formulation for a longer time. The delayed release of the drug from MSN-NH2-FU-FA indicates that it can act as an efficient drug carrier and could minimize the exposure of anticancer agents to normal tissues and enhance the accumulation in tumor tissues [ 37 ].…”

“…Solid lipid nanoparticles Colorectal Enhanced anticancer activity [32] Chitosan nanoparticles Colorectal Better targeting efficiency and localized drug in cancer cells [33] PLGA nanoparticles Colorectal Maximum cell-lysis effect and better targeting efficiency [34,35] Citrus pectin nanoparticles coated with Eudragit S100 Colorectal Prolonged drug release and enhance selectivity [36] Silica nanoparticles conjugated to hyalurocin acid Colon Enhanced cellular uptake and improved cytotoxicity [37] Aminofunctionalized MSN Colorectal Improved cytotoxicity and pH-responsive controlled drug release system [38] Alginate-chitosan nanoparticles Ocular application Enhanced ocular absorption and pharmacokinetics [39] Galactosylated chitosan functionalized MSN Colon cancer Enhanced anti-cancer activity and targeting [16] Chitosan and PEG coated MSNs Breast and cervical cancer Enhanced anti-cancer activity with the loading of two anticancer drugs [19] MSN Melanoma Enhanced anti-cancer activity and skin permeation [30] Carboxymethyl chitosan-coated MSN Ocular application Enhance ocular absorption and pharmacokinetic [31] Combination of 5-FU and cisplatin with electroporation Ovarian Enhanced anti-cancer activity [40] Folic acid and PLGA conjugates Colorectal Enhanced anticancer activity [41] Folate-conjugated polymers Colon Enhanced anti-cancer activity and targeting [42] PLGA folate-conjugated peptide nanoparticles Melanoma Enhanced cytotoxicity and targeting [43] Bi-MIL-88B MOF nanoparticles coated with chitosan-folic acid conjugate Colon Enhanced anti-cancer activity and targeting [44] MSN nanoparticles coated with folic acid-modified lipid Breast cancer Enhanced cytotoxicity and targeting with the loading of two anticancer drugs [45] 2. Materials and Methods…”

Novel Approaches For Colon Site-Specific Drug Delivery: An Overview Of Recent Advancements

“…As CD44 is overexpressed in many malignancies and HA has a strong attraction for it, target-selective drug administration using HA-conjugated drug delivery devices has been investigated [111]. For instance, earlier research [111,112] looked at the efficiency of mesoporous silica nanoparticles enhanced with HA in focusing on cancer cells that overexpress CD44. In order to target inflamed intestinal mucosa, Vafaei et al [113] created self-assembled HA nanoparticles for colonic delivery of budesonide.…”