Limits...
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

Cytotoxicity assay.Notes: (A) The toxicity of blank nanoparticles on colo-205 cancer cells, (B) cytotoxicity of 5-FU, 5-FU/SNP, and 5-FU/HSNP in colo-205 colon cancer cells. All experiments were done by MTT assay in four replicates from three independent experiments. Data was represented as mean ± SD. (C) Morphological images of cancer cells upon treatment with the respective formulations. *P<0.05.Abbreviations: 5-FU, 5-fluorouracil; HSNP, hyaluronic acid-conjugated silica nanoparticles; SNP, silica nanoparticles; NP, nanoparticles.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4608620&req=5

f5-ijn-10-6445: Cytotoxicity assay.Notes: (A) The toxicity of blank nanoparticles on colo-205 cancer cells, (B) cytotoxicity of 5-FU, 5-FU/SNP, and 5-FU/HSNP in colo-205 colon cancer cells. All experiments were done by MTT assay in four replicates from three independent experiments. Data was represented as mean ± SD. (C) Morphological images of cancer cells upon treatment with the respective formulations. *P<0.05.Abbreviations: 5-FU, 5-fluorouracil; HSNP, hyaluronic acid-conjugated silica nanoparticles; SNP, silica nanoparticles; NP, nanoparticles.

Mentions: The cytotoxicity of blank nanoparticle was investigated in Colo-205 colon cancer cells. The cells were treated with individual formulations at various concentrations and incubated for 24 hours. As seen from Figure 5A, blank NP did not induce any appreciable toxicity, and the cell viability remained more than 85% throughout all the concentrations tested. The high cell viability of blank NP indicates its excellent biocompatibility and would be suitable for the systemic administration or cancer targeting. It is worth noting that at highest concentration (100 µg/mL), bare SNP exhibited ~85% cell viability, whereas HA-conjugation on the surface significantly improved the cell viability indicating its excellent biocompatibility.


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)

Cytotoxicity assay.Notes: (A) The toxicity of blank nanoparticles on colo-205 cancer cells, (B) cytotoxicity of 5-FU, 5-FU/SNP, and 5-FU/HSNP in colo-205 colon cancer cells. All experiments were done by MTT assay in four replicates from three independent experiments. Data was represented as mean ± SD. (C) Morphological images of cancer cells upon treatment with the respective formulations. *P<0.05.Abbreviations: 5-FU, 5-fluorouracil; HSNP, hyaluronic acid-conjugated silica nanoparticles; SNP, silica nanoparticles; NP, nanoparticles.
© Copyright Policy
Related In: Results  -  Collection

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

f5-ijn-10-6445: Cytotoxicity assay.Notes: (A) The toxicity of blank nanoparticles on colo-205 cancer cells, (B) cytotoxicity of 5-FU, 5-FU/SNP, and 5-FU/HSNP in colo-205 colon cancer cells. All experiments were done by MTT assay in four replicates from three independent experiments. Data was represented as mean ± SD. (C) Morphological images of cancer cells upon treatment with the respective formulations. *P<0.05.Abbreviations: 5-FU, 5-fluorouracil; HSNP, hyaluronic acid-conjugated silica nanoparticles; SNP, silica nanoparticles; NP, nanoparticles.
Mentions: The cytotoxicity of blank nanoparticle was investigated in Colo-205 colon cancer cells. The cells were treated with individual formulations at various concentrations and incubated for 24 hours. As seen from Figure 5A, blank NP did not induce any appreciable toxicity, and the cell viability remained more than 85% throughout all the concentrations tested. The high cell viability of blank NP indicates its excellent biocompatibility and would be suitable for the systemic administration or cancer targeting. It is worth noting that at highest concentration (100 µg/mL), bare SNP exhibited ~85% cell viability, whereas HA-conjugation on the surface significantly improved the cell viability indicating its excellent biocompatibility.

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