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Int J Nanomedicine. 2015 Oct 12;10:6445-54. doi: 10.2147/IJN.S89476. eCollection 2015.

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

Author information

1
Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, People's Republic of China.
2
Department of Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, People's Republic of China.
3
Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, People's Republic of China.
4
Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, People's Republic of China.
5
Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, People's Republic of China.
6
Department of Internal Medicine, Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan, People's Republic of China.
7
Department of Breast Disease Center, Shandong Cancer Hospital and Institute, Jinan, People's Republic of China.

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.

KEYWORDS:

5-fluorouracil; apoptosis; colon cancer; hyaluronic acid; nanoparticles

PMID:
26491300
PMCID:
PMC4608620
DOI:
10.2147/IJN.S89476
[Indexed for MEDLINE]
Free PMC Article

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