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

In vitro release profile of 5-FU/SNP and 5-FU/HSNP in phosphate-buffered saline (pH =7.4) at 37°C.Notes: The release study was conducted up to 120 hours, and the amount of drug released was evaluated by means of HPLC technique. *P<0.05.Abbreviations: HPLC, high performance liquid chromatography; 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

f3-ijn-10-6445: In vitro release profile of 5-FU/SNP and 5-FU/HSNP in phosphate-buffered saline (pH =7.4) at 37°C.Notes: The release study was conducted up to 120 hours, and the amount of drug released was evaluated by means of HPLC technique. *P<0.05.Abbreviations: HPLC, high performance liquid chromatography; 5-FU, 5-fluorouracil; HSNP, hyaluronic acid-conjugated silica nanoparticles; SNP, silica nanoparticles.

Mentions: The in vitro release study of 5-FU/SNP and 5-FU/HSNP was performed in PBS (pH 7.4) at 37°C (Figure 3). The data suggested that the rate of 5-FU release was significantly slower in HA-conjugated nanoparticle than SiNPs. It can be clearly seen that nearly ~30% of drug was released from SNP, whereas only ~18% of drug was released from HSNP in 24 hours. The trend continued until the end of release study wherein nearly 100% of drug released from SNP compared with ~70% from HSNP. The difference in drug release between the two carriers could be due to the presence of HA on the surface of nanoparticles. The delayed release of drug from HSNP indicates that it can act as an efficient drug carrier and could minimize the exposure of chemotherapeutic agents to normal tissues and increase the accumulation in tumor tissues.19


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)

In vitro release profile of 5-FU/SNP and 5-FU/HSNP in phosphate-buffered saline (pH =7.4) at 37°C.Notes: The release study was conducted up to 120 hours, and the amount of drug released was evaluated by means of HPLC technique. *P<0.05.Abbreviations: HPLC, high performance liquid chromatography; 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

f3-ijn-10-6445: In vitro release profile of 5-FU/SNP and 5-FU/HSNP in phosphate-buffered saline (pH =7.4) at 37°C.Notes: The release study was conducted up to 120 hours, and the amount of drug released was evaluated by means of HPLC technique. *P<0.05.Abbreviations: HPLC, high performance liquid chromatography; 5-FU, 5-fluorouracil; HSNP, hyaluronic acid-conjugated silica nanoparticles; SNP, silica nanoparticles.
Mentions: The in vitro release study of 5-FU/SNP and 5-FU/HSNP was performed in PBS (pH 7.4) at 37°C (Figure 3). The data suggested that the rate of 5-FU release was significantly slower in HA-conjugated nanoparticle than SiNPs. It can be clearly seen that nearly ~30% of drug was released from SNP, whereas only ~18% of drug was released from HSNP in 24 hours. The trend continued until the end of release study wherein nearly 100% of drug released from SNP compared with ~70% from HSNP. The difference in drug release between the two carriers could be due to the presence of HA on the surface of nanoparticles. The delayed release of drug from HSNP indicates that it can act as an efficient drug carrier and could minimize the exposure of chemotherapeutic agents to normal tissues and increase the accumulation in tumor tissues.19

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