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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

Cellular uptake of targeted and non-targeted nanoparticles.Notes: (A) Intracellular uptake of 5-FU/SNP and 5-FU/HSNP in colo-205 colon cancer cells. Rhodamine-B was used as a fluorescent dye. The uptake is shown as a percentage of total amounts of NP (dye) incubated with the cancer cells. (B) Representative confocal microscopy images of 5-FU/HSNP in colo-205 cancer cells. The cells are stained with Lysotracker lysosomal stain, and DAPI was used to stain the nucleus. *P<0.05, **P<0.01.Abbreviations: 5-FU, 5-fluorouracil; HSNP, hyaluronic acid-conjugated silica nanoparticles; SNP, silica nanoparticles; NP, nanoparticle.
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f4-ijn-10-6445: Cellular uptake of targeted and non-targeted nanoparticles.Notes: (A) Intracellular uptake of 5-FU/SNP and 5-FU/HSNP in colo-205 colon cancer cells. Rhodamine-B was used as a fluorescent dye. The uptake is shown as a percentage of total amounts of NP (dye) incubated with the cancer cells. (B) Representative confocal microscopy images of 5-FU/HSNP in colo-205 cancer cells. The cells are stained with Lysotracker lysosomal stain, and DAPI was used to stain the nucleus. *P<0.05, **P<0.01.Abbreviations: 5-FU, 5-fluorouracil; HSNP, hyaluronic acid-conjugated silica nanoparticles; SNP, silica nanoparticles; NP, nanoparticle.

Mentions: 5-FU was replaced with rhodamine-B to investigate the cellular uptake potential of targeted and nontargeted nanoparticles. The specific binding affinity of HA toward the CD44 overexpressing colon cancer cell was evaluated by means of cellular uptake study. As seen from Figure 4A, colo-205 cells incubated with SNP and HSNP showed remarkable uptake in a time-dependent manner. Specifically, HA-conjugated NP showed a significantly higher uptake throughout the study period. The variations in the uptake of different formulations could have occurred due to the different mechanisms of uptake. The SNP could be internalized due to the simple energy-dependent process via endocytosis receptor, whereas HSNP could be internalized by the specific CD44-mediated cellular pathways. The influence of targeting ligand on the NP surface was clearly visible after 4 hours of incubation, wherein HSNP exhibited >45% of cellular internalization compared with 20% for nontargeted NP. The trend continued up to 24 hours. These results are consistent with the previous observation wherein it has been shown that HA coating enhances the permeability of 5-FU containing nanoparticles by a receptor-mediated internalization.21 From the results, it is apparent that the actively targeted nanoparticles will deliver more anticancer agent to cancer cell than the nontargeted one. These data suggest a role for receptor-mediated internalization of the actively targeted HSNP.


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)

Cellular uptake of targeted and non-targeted nanoparticles.Notes: (A) Intracellular uptake of 5-FU/SNP and 5-FU/HSNP in colo-205 colon cancer cells. Rhodamine-B was used as a fluorescent dye. The uptake is shown as a percentage of total amounts of NP (dye) incubated with the cancer cells. (B) Representative confocal microscopy images of 5-FU/HSNP in colo-205 cancer cells. The cells are stained with Lysotracker lysosomal stain, and DAPI was used to stain the nucleus. *P<0.05, **P<0.01.Abbreviations: 5-FU, 5-fluorouracil; HSNP, hyaluronic acid-conjugated silica nanoparticles; SNP, silica nanoparticles; NP, nanoparticle.
© Copyright Policy
Related In: Results  -  Collection

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

f4-ijn-10-6445: Cellular uptake of targeted and non-targeted nanoparticles.Notes: (A) Intracellular uptake of 5-FU/SNP and 5-FU/HSNP in colo-205 colon cancer cells. Rhodamine-B was used as a fluorescent dye. The uptake is shown as a percentage of total amounts of NP (dye) incubated with the cancer cells. (B) Representative confocal microscopy images of 5-FU/HSNP in colo-205 cancer cells. The cells are stained with Lysotracker lysosomal stain, and DAPI was used to stain the nucleus. *P<0.05, **P<0.01.Abbreviations: 5-FU, 5-fluorouracil; HSNP, hyaluronic acid-conjugated silica nanoparticles; SNP, silica nanoparticles; NP, nanoparticle.
Mentions: 5-FU was replaced with rhodamine-B to investigate the cellular uptake potential of targeted and nontargeted nanoparticles. The specific binding affinity of HA toward the CD44 overexpressing colon cancer cell was evaluated by means of cellular uptake study. As seen from Figure 4A, colo-205 cells incubated with SNP and HSNP showed remarkable uptake in a time-dependent manner. Specifically, HA-conjugated NP showed a significantly higher uptake throughout the study period. The variations in the uptake of different formulations could have occurred due to the different mechanisms of uptake. The SNP could be internalized due to the simple energy-dependent process via endocytosis receptor, whereas HSNP could be internalized by the specific CD44-mediated cellular pathways. The influence of targeting ligand on the NP surface was clearly visible after 4 hours of incubation, wherein HSNP exhibited >45% of cellular internalization compared with 20% for nontargeted NP. The trend continued up to 24 hours. These results are consistent with the previous observation wherein it has been shown that HA coating enhances the permeability of 5-FU containing nanoparticles by a receptor-mediated internalization.21 From the results, it is apparent that the actively targeted nanoparticles will deliver more anticancer agent to cancer cell than the nontargeted one. These data suggest a role for receptor-mediated internalization of the actively targeted HSNP.

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