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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

Cell apoptosis observed by Hoechst 33342 staining.Notes: Cells were treated with 5-FU, 5-FU/SNP, and 5-FU/HSNP for 24 hours, subsequently stained, and observed under UV light or white lightAbbreviations: 5-FU, 5-fluorouracil; HSNP, hyaluronic acid-conjugated silica nanoparticles; SNP, silica nanoparticles; NP, nanoparticles.
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f6-ijn-10-6445: Cell apoptosis observed by Hoechst 33342 staining.Notes: Cells were treated with 5-FU, 5-FU/SNP, and 5-FU/HSNP for 24 hours, subsequently stained, and observed under UV light or white lightAbbreviations: 5-FU, 5-fluorouracil; HSNP, hyaluronic acid-conjugated silica nanoparticles; SNP, silica nanoparticles; NP, nanoparticles.

Mentions: The cytotoxic effect of individual formulation was studied by Hoechst staining and visualized by DM6000CS, Leica Microsystems, Wetzlar, Germany. Untreated cells were homogeneously tarnished blue, with few or no apoptotic cells existed as shown in Figure 6. The control cells maintained a definite morphology with clear boundary. The exposure of free drug slightly fragmented the cancer cells; however, remarkable apoptosis was observed in 5-FU/HSNP-treated cancer cell group. The 5-FU/HSNP-treated group showed highly condensed cell, had thick-stained nuclei, and had fragmented chromatin and apoptotic bodies. The qualitative apoptosis study was consistent with the cytotoxicity study in which HA-conjugated nanoparticles showed a superior anticancer activity.


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)

Cell apoptosis observed by Hoechst 33342 staining.Notes: Cells were treated with 5-FU, 5-FU/SNP, and 5-FU/HSNP for 24 hours, subsequently stained, and observed under UV light or white lightAbbreviations: 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

f6-ijn-10-6445: Cell apoptosis observed by Hoechst 33342 staining.Notes: Cells were treated with 5-FU, 5-FU/SNP, and 5-FU/HSNP for 24 hours, subsequently stained, and observed under UV light or white lightAbbreviations: 5-FU, 5-fluorouracil; HSNP, hyaluronic acid-conjugated silica nanoparticles; SNP, silica nanoparticles; NP, nanoparticles.
Mentions: The cytotoxic effect of individual formulation was studied by Hoechst staining and visualized by DM6000CS, Leica Microsystems, Wetzlar, Germany. Untreated cells were homogeneously tarnished blue, with few or no apoptotic cells existed as shown in Figure 6. The control cells maintained a definite morphology with clear boundary. The exposure of free drug slightly fragmented the cancer cells; however, remarkable apoptosis was observed in 5-FU/HSNP-treated cancer cell group. The 5-FU/HSNP-treated group showed highly condensed cell, had thick-stained nuclei, and had fragmented chromatin and apoptotic bodies. The qualitative apoptosis study was consistent with the cytotoxicity study in which HA-conjugated nanoparticles showed a superior anticancer activity.

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