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

Liu K, Wang ZQ, Wang SJ, Liu P, Qin YH, Ma Y, Li XC, Huo ZJ - Int J Nanomedicine (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong University, 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.

No MeSH data available.


Related in: MedlinePlus

Schematic illustration of preparation of hyaluronic acid-conjugated silica nanoparticles.Notes: 5-fluorouracil was used as a model drug to load in the nanoparticles. The carboxylic group of HA was activated and conjugated with the amine functional group of silica nanoparticles.Abbreviations: HA, hyaluronic acid; 5-FU, 5-fluorouracil; NP, nanoparticles.
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f1-ijn-10-6445: Schematic illustration of preparation of hyaluronic acid-conjugated silica nanoparticles.Notes: 5-fluorouracil was used as a model drug to load in the nanoparticles. The carboxylic group of HA was activated and conjugated with the amine functional group of silica nanoparticles.Abbreviations: HA, hyaluronic acid; 5-FU, 5-fluorouracil; NP, nanoparticles.

Mentions: Colon cancer is regarded as one of the most common cancers with high rate of morbidity and mortality. In this regard, chemotherapy is the most convenient and preferred treatment modality to improve patient’s profile and quality of life. 5-FU is used as a first-line chemotherapeutic drug in colorectal cancers, and immediately after surgery as an adjuvant therapy. 5-FU is a thymidylate synthase inhibitor (interferes DNA synthesis), which acts by arresting cancer cell growth at S-phase of cell cycle. However, intravenous administration of 5-FU results in large systemic distribution, with only a small fraction of the dose reaching the site of action. Therefore, it is utmost necessary to develop a nano drug delivery system to increase the therapeutic performance of 5-FU. In the present study, SiNP was used owing to its unique advantages such as excellent biocompatibility, high hydrophobicity, systemic stability, and resistant to pH changes, and also, it could be largely multifunctional. Furthermore, HA was conjugated on the surface of SiNP. Before conjugation of HA to the silica NP, HA was activated to expose free carboxylic acid group. The carboxylic group of HA was conjugated with the amine functional group of silica (Figure 1). The HA, which is composed of N-acetyl-D-glucosamine and D-glucuronic acid, interacts with the CDD4 overexpressing cancer cells. HA-based targeting delivery systems are expected to show great potential in clinical applications. The focus of this work was to use HA-SiNP to encapsulate 5-FU and deliver to colon cancer cells.


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

Liu K, Wang ZQ, Wang SJ, Liu P, Qin YH, Ma Y, Li XC, Huo ZJ - Int J Nanomedicine (2015)

Schematic illustration of preparation of hyaluronic acid-conjugated silica nanoparticles.Notes: 5-fluorouracil was used as a model drug to load in the nanoparticles. The carboxylic group of HA was activated and conjugated with the amine functional group of silica nanoparticles.Abbreviations: HA, hyaluronic acid; 5-FU, 5-fluorouracil; NP, nanoparticles.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608620&req=5

f1-ijn-10-6445: Schematic illustration of preparation of hyaluronic acid-conjugated silica nanoparticles.Notes: 5-fluorouracil was used as a model drug to load in the nanoparticles. The carboxylic group of HA was activated and conjugated with the amine functional group of silica nanoparticles.Abbreviations: HA, hyaluronic acid; 5-FU, 5-fluorouracil; NP, nanoparticles.
Mentions: Colon cancer is regarded as one of the most common cancers with high rate of morbidity and mortality. In this regard, chemotherapy is the most convenient and preferred treatment modality to improve patient’s profile and quality of life. 5-FU is used as a first-line chemotherapeutic drug in colorectal cancers, and immediately after surgery as an adjuvant therapy. 5-FU is a thymidylate synthase inhibitor (interferes DNA synthesis), which acts by arresting cancer cell growth at S-phase of cell cycle. However, intravenous administration of 5-FU results in large systemic distribution, with only a small fraction of the dose reaching the site of action. Therefore, it is utmost necessary to develop a nano drug delivery system to increase the therapeutic performance of 5-FU. In the present study, SiNP was used owing to its unique advantages such as excellent biocompatibility, high hydrophobicity, systemic stability, and resistant to pH changes, and also, it could be largely multifunctional. Furthermore, HA was conjugated on the surface of SiNP. Before conjugation of HA to the silica NP, HA was activated to expose free carboxylic acid group. The carboxylic group of HA was conjugated with the amine functional group of silica (Figure 1). The HA, which is composed of N-acetyl-D-glucosamine and D-glucuronic acid, interacts with the CDD4 overexpressing cancer cells. HA-based targeting delivery systems are expected to show great potential in clinical applications. The focus of this work was to use HA-SiNP to encapsulate 5-FU and deliver to colon cancer cells.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong University, 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.

No MeSH data available.


Related in: MedlinePlus