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

Antitumor efficacy of different formulations.Notes: (A) Tumor inhibitory effect of different formulations on colon cancer cell bearing xenograft tumor model. The antitumor efficacy study was carried up to 20 days. (B) H&E staining. (C) Ki67 immunohistochemical study in extracted tumor. H&E staining: Eosin is an acidic dye, and it stains basic (or acidophilic) structures red or pink. Hematoxylin can be considered as a basic dye (general formula for basic dyes is dye+Cl-). Hematoxylin is actually a dye called hematein (obtained from the log-wood tree) used in combination with aluminium ions (Al3+). Ki-67 is a protein in cells that increases as they prepare to divide into new cells. A staining process can measure the percentage of tumor cells that are positive for Ki-67. The more positive cells are present, the more quickly they are dividing and forming new cells and more densely they are stained. **P<0.01, ***P<0.001.Abbreviations: 5-FU, 5-fluorouracil; HSNP, hyaluronic acid-conjugated silica nanoparticles; SNP, silica nanoparticles.
© Copyright Policy
Related In: Results  -  Collection

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

f8-ijn-10-6445: Antitumor efficacy of different formulations.Notes: (A) Tumor inhibitory effect of different formulations on colon cancer cell bearing xenograft tumor model. The antitumor efficacy study was carried up to 20 days. (B) H&E staining. (C) Ki67 immunohistochemical study in extracted tumor. H&E staining: Eosin is an acidic dye, and it stains basic (or acidophilic) structures red or pink. Hematoxylin can be considered as a basic dye (general formula for basic dyes is dye+Cl-). Hematoxylin is actually a dye called hematein (obtained from the log-wood tree) used in combination with aluminium ions (Al3+). Ki-67 is a protein in cells that increases as they prepare to divide into new cells. A staining process can measure the percentage of tumor cells that are positive for Ki-67. The more positive cells are present, the more quickly they are dividing and forming new cells and more densely they are stained. **P<0.01, ***P<0.001.Abbreviations: 5-FU, 5-fluorouracil; HSNP, hyaluronic acid-conjugated silica nanoparticles; SNP, silica nanoparticles.

Mentions: The antitumor efficacy of individual formulations was tested in xenograft tumor model. As shown in Figure 8A, tumor volume constantly increased in case of untreated mice group. The free drug, though inhibited the progression of tumor to an extent, is far behind the reasonable antitumor response. Consistent with the in vitro studies, HSNP was highly efficient in suppressing the tumor growth. The remarkable antitumor response might be attributed to the targeting ability of HA, which is present on the surface of nanoparticles. The targeting moiety could enhance the concentration of 5-FU within the tumor tissues.


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)

Antitumor efficacy of different formulations.Notes: (A) Tumor inhibitory effect of different formulations on colon cancer cell bearing xenograft tumor model. The antitumor efficacy study was carried up to 20 days. (B) H&E staining. (C) Ki67 immunohistochemical study in extracted tumor. H&E staining: Eosin is an acidic dye, and it stains basic (or acidophilic) structures red or pink. Hematoxylin can be considered as a basic dye (general formula for basic dyes is dye+Cl-). Hematoxylin is actually a dye called hematein (obtained from the log-wood tree) used in combination with aluminium ions (Al3+). Ki-67 is a protein in cells that increases as they prepare to divide into new cells. A staining process can measure the percentage of tumor cells that are positive for Ki-67. The more positive cells are present, the more quickly they are dividing and forming new cells and more densely they are stained. **P<0.01, ***P<0.001.Abbreviations: 5-FU, 5-fluorouracil; HSNP, hyaluronic acid-conjugated silica nanoparticles; SNP, silica nanoparticles.
© Copyright Policy
Related In: Results  -  Collection

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

f8-ijn-10-6445: Antitumor efficacy of different formulations.Notes: (A) Tumor inhibitory effect of different formulations on colon cancer cell bearing xenograft tumor model. The antitumor efficacy study was carried up to 20 days. (B) H&E staining. (C) Ki67 immunohistochemical study in extracted tumor. H&E staining: Eosin is an acidic dye, and it stains basic (or acidophilic) structures red or pink. Hematoxylin can be considered as a basic dye (general formula for basic dyes is dye+Cl-). Hematoxylin is actually a dye called hematein (obtained from the log-wood tree) used in combination with aluminium ions (Al3+). Ki-67 is a protein in cells that increases as they prepare to divide into new cells. A staining process can measure the percentage of tumor cells that are positive for Ki-67. The more positive cells are present, the more quickly they are dividing and forming new cells and more densely they are stained. **P<0.01, ***P<0.001.Abbreviations: 5-FU, 5-fluorouracil; HSNP, hyaluronic acid-conjugated silica nanoparticles; SNP, silica nanoparticles.
Mentions: The antitumor efficacy of individual formulations was tested in xenograft tumor model. As shown in Figure 8A, tumor volume constantly increased in case of untreated mice group. The free drug, though inhibited the progression of tumor to an extent, is far behind the reasonable antitumor response. Consistent with the in vitro studies, HSNP was highly efficient in suppressing the tumor growth. The remarkable antitumor response might be attributed to the targeting ability of HA, which is present on the surface of nanoparticles. The targeting moiety could enhance the concentration of 5-FU within the tumor tissues.

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