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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

Physicochemical characterization of 5-FU/HSNP.Notes: (A) Particle size distribution of 5-FU/HSNP, (B) transmission electron microscope images of 5-FU/HSNP.Abbreviations: 5-FU, 5-fluorouracil; HSNP, hyaluronic acid-conjugated silica nanoparticles.
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f2-ijn-10-6445: Physicochemical characterization of 5-FU/HSNP.Notes: (A) Particle size distribution of 5-FU/HSNP, (B) transmission electron microscope images of 5-FU/HSNP.Abbreviations: 5-FU, 5-fluorouracil; HSNP, hyaluronic acid-conjugated silica nanoparticles.

Mentions: HA-SiNP was applied in order to improve the anticancer efficacy of 5-FU and to reduce its associated side effects. 5-FU was efficiently loaded into the core of Si NP with a high loading efficiency. The loading efficiency of 5-FU in NP was observed to be ~>90% with a high loading capacity of >15%. The conjugation of HA to the SiNP did not alter the loading efficiency of 5-FU. The average particle size of SNP and HSNP was observed to be ~95±2.3 nm and 138±3.4 nm, respectively (Figure 2A). The polydispersity index represented a uniform mono-dispersion with PDI ~0.12. It has been well documented that particles of <200 nm are more advantageous as nanoparticles of reduced particle size could effectively increase the blood circulation profile of anticancer drugs and thereby avoid the reticuloendothelial system-mediated systemic clearance and passively target the anticancer drug to the tumor tissues.18


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)

Physicochemical characterization of 5-FU/HSNP.Notes: (A) Particle size distribution of 5-FU/HSNP, (B) transmission electron microscope images of 5-FU/HSNP.Abbreviations: 5-FU, 5-fluorouracil; HSNP, hyaluronic acid-conjugated silica nanoparticles.
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Related In: Results  -  Collection

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

f2-ijn-10-6445: Physicochemical characterization of 5-FU/HSNP.Notes: (A) Particle size distribution of 5-FU/HSNP, (B) transmission electron microscope images of 5-FU/HSNP.Abbreviations: 5-FU, 5-fluorouracil; HSNP, hyaluronic acid-conjugated silica nanoparticles.
Mentions: HA-SiNP was applied in order to improve the anticancer efficacy of 5-FU and to reduce its associated side effects. 5-FU was efficiently loaded into the core of Si NP with a high loading efficiency. The loading efficiency of 5-FU in NP was observed to be ~>90% with a high loading capacity of >15%. The conjugation of HA to the SiNP did not alter the loading efficiency of 5-FU. The average particle size of SNP and HSNP was observed to be ~95±2.3 nm and 138±3.4 nm, respectively (Figure 2A). The polydispersity index represented a uniform mono-dispersion with PDI ~0.12. It has been well documented that particles of <200 nm are more advantageous as nanoparticles of reduced particle size could effectively increase the blood circulation profile of anticancer drugs and thereby avoid the reticuloendothelial system-mediated systemic clearance and passively target the anticancer drug to the tumor tissues.18

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