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A cell-targeted chemotherapeutic nanomedicine strategy for oral squamous cell carcinoma therapy.

Wang ZQ, Liu K, Huo ZJ, Li XC, Wang M, Liu P, Pang B, Wang SJ - J Nanobiotechnology (2015)

Bottom Line: Furthermore, Live/Dead assay showed a higher extent of red fluorescence was observed for the cells exposed with PLGA/NR7 than compared with non-targeted PLGA NP.Altogether, our results show the feasibility and promise of a cell-targeted anticancer nanomedicine strategy that can be effective for the treatment of oral squamous cell carcinoma.The present work might be of great importance to the further exploration of the potential application of PLGA/NR7 in the clinically relevant animal models.

View Article: PubMed Central - PubMed

Affiliation: Department of Head and Neck Surgery, Shandong Cancer Hospital and Institute, Jinan, 250117, China. zhiqiwang@126.com.

ABSTRACT

Background: Oral squamous cell carcinoma (OSCC) or cancers of oral cavity is one of the most common cancers worldwide with high rate of mortality and morbidity. At present, chemotherapy is one of the most effective treatments; however it often fails to meet the requirements in the clinical therapy. In the present study, we have successfully formulated ligand-decorated cancer-targeted CDDP-loaded PLGA-PEG/NR7 nanoparticles and demonstrated the feasibility of using NR7 peptide for targeted delivery, rapid intracellular uptake, and enhanced cytotoxic effect in receptor-overexpressed OSCC cancer cells.

Results: Nanosized particles were formed and sustained release patterns were observed for PLGA/NR7 nanoparticles. Significantly higher cellular uptake was observed in HN6 OSCC cancer cells and superior anticancer effects are observed from the optimized targeted nanoparticles. Furthermore, Live/Dead assay showed a higher extent of red fluorescence was observed for the cells exposed with PLGA/NR7 than compared with non-targeted PLGA NP. The presence of the NR7-targeting moiety on the surface of PLGA carriers could allow the specific receptor-mediated internalization, enhanced cellular uptake, and higher cell killing potency. Especially, PLGA/NR7 NP exhibited a superior apoptosis effect in HN6 cancer cells with around ~45 % (early and late apoptotic stage) and ~59 % after 24 and 48 h incubation, respectively. It is apparent that the actively targeted micelles will deliver more anticancer agent to cancer cell than non-targeted one.

Conclusion: Altogether, our results show the feasibility and promise of a cell-targeted anticancer nanomedicine strategy that can be effective for the treatment of oral squamous cell carcinoma. The present work might be of great importance to the further exploration of the potential application of PLGA/NR7 in the clinically relevant animal models.

No MeSH data available.


Related in: MedlinePlus

a Intracellular uptake of PLGA NP and PLGA/NR7 NP in HN6 squamous cell carcinoma. 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 targeted and non-targeted NP in HN6 cancer cells. The cells are stained with Lysotracker lysosomal stain and DAPI was used to stain the nucleus. **p < 0.01 and *p < 005 is the statistical difference between the cellular uptake of two formulations
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Fig4: a Intracellular uptake of PLGA NP and PLGA/NR7 NP in HN6 squamous cell carcinoma. 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 targeted and non-targeted NP in HN6 cancer cells. The cells are stained with Lysotracker lysosomal stain and DAPI was used to stain the nucleus. **p < 0.01 and *p < 005 is the statistical difference between the cellular uptake of two formulations

Mentions: Quantitative and fluorescent studies were performed to investigate the binding affinity of targeted and non-targeted polymeric micelles. For this purpose, PLGA NP was loaded with Rho B fluorescent dye instead of CDDP. As seen from Fig. 4a, cells incubated with PLGA and PLGA/NR7 NP showed appreciable intracellular uptake. Notably, NR7 conjugated polymeric nanoparticle showed significantly (p < 0.01) higher cellular uptake than that of non-targeted PLGA NP. The influence of targeting ligand on the NP surface was visible immediately after 1 h of incubation, wherein PLGA/NR7 NP exhibited more than 20 % of cellular internalization compared to <10 % for non-targeted NP. The trend continued up to 24 h. Two different phase of cellular uptake was observed. First, steady or faster rate of cell uptake was seen in first 12 h of study, followed by a relatively slower cellular uptake (of less than 10 %). Overall, PLGA/NR7 NP showed ~70 % of NP uptake comparing to meagre ~34 % for PLGA NP. From the result, it is apparent that the actively targeted micelles will deliver more anticancer agent to cancer cell than non-targeted one. These data suggest a role for receptor-mediated internalization of the actively targeted PLGA/NR7 NP.Fig. 4


A cell-targeted chemotherapeutic nanomedicine strategy for oral squamous cell carcinoma therapy.

Wang ZQ, Liu K, Huo ZJ, Li XC, Wang M, Liu P, Pang B, Wang SJ - J Nanobiotechnology (2015)

a Intracellular uptake of PLGA NP and PLGA/NR7 NP in HN6 squamous cell carcinoma. 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 targeted and non-targeted NP in HN6 cancer cells. The cells are stained with Lysotracker lysosomal stain and DAPI was used to stain the nucleus. **p < 0.01 and *p < 005 is the statistical difference between the cellular uptake of two formulations
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4591064&req=5

Fig4: a Intracellular uptake of PLGA NP and PLGA/NR7 NP in HN6 squamous cell carcinoma. 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 targeted and non-targeted NP in HN6 cancer cells. The cells are stained with Lysotracker lysosomal stain and DAPI was used to stain the nucleus. **p < 0.01 and *p < 005 is the statistical difference between the cellular uptake of two formulations
Mentions: Quantitative and fluorescent studies were performed to investigate the binding affinity of targeted and non-targeted polymeric micelles. For this purpose, PLGA NP was loaded with Rho B fluorescent dye instead of CDDP. As seen from Fig. 4a, cells incubated with PLGA and PLGA/NR7 NP showed appreciable intracellular uptake. Notably, NR7 conjugated polymeric nanoparticle showed significantly (p < 0.01) higher cellular uptake than that of non-targeted PLGA NP. The influence of targeting ligand on the NP surface was visible immediately after 1 h of incubation, wherein PLGA/NR7 NP exhibited more than 20 % of cellular internalization compared to <10 % for non-targeted NP. The trend continued up to 24 h. Two different phase of cellular uptake was observed. First, steady or faster rate of cell uptake was seen in first 12 h of study, followed by a relatively slower cellular uptake (of less than 10 %). Overall, PLGA/NR7 NP showed ~70 % of NP uptake comparing to meagre ~34 % for PLGA NP. From the result, it is apparent that the actively targeted micelles will deliver more anticancer agent to cancer cell than non-targeted one. These data suggest a role for receptor-mediated internalization of the actively targeted PLGA/NR7 NP.Fig. 4

Bottom Line: Furthermore, Live/Dead assay showed a higher extent of red fluorescence was observed for the cells exposed with PLGA/NR7 than compared with non-targeted PLGA NP.Altogether, our results show the feasibility and promise of a cell-targeted anticancer nanomedicine strategy that can be effective for the treatment of oral squamous cell carcinoma.The present work might be of great importance to the further exploration of the potential application of PLGA/NR7 in the clinically relevant animal models.

View Article: PubMed Central - PubMed

Affiliation: Department of Head and Neck Surgery, Shandong Cancer Hospital and Institute, Jinan, 250117, China. zhiqiwang@126.com.

ABSTRACT

Background: Oral squamous cell carcinoma (OSCC) or cancers of oral cavity is one of the most common cancers worldwide with high rate of mortality and morbidity. At present, chemotherapy is one of the most effective treatments; however it often fails to meet the requirements in the clinical therapy. In the present study, we have successfully formulated ligand-decorated cancer-targeted CDDP-loaded PLGA-PEG/NR7 nanoparticles and demonstrated the feasibility of using NR7 peptide for targeted delivery, rapid intracellular uptake, and enhanced cytotoxic effect in receptor-overexpressed OSCC cancer cells.

Results: Nanosized particles were formed and sustained release patterns were observed for PLGA/NR7 nanoparticles. Significantly higher cellular uptake was observed in HN6 OSCC cancer cells and superior anticancer effects are observed from the optimized targeted nanoparticles. Furthermore, Live/Dead assay showed a higher extent of red fluorescence was observed for the cells exposed with PLGA/NR7 than compared with non-targeted PLGA NP. The presence of the NR7-targeting moiety on the surface of PLGA carriers could allow the specific receptor-mediated internalization, enhanced cellular uptake, and higher cell killing potency. Especially, PLGA/NR7 NP exhibited a superior apoptosis effect in HN6 cancer cells with around ~45 % (early and late apoptotic stage) and ~59 % after 24 and 48 h incubation, respectively. It is apparent that the actively targeted micelles will deliver more anticancer agent to cancer cell than non-targeted one.

Conclusion: Altogether, our results show the feasibility and promise of a cell-targeted anticancer nanomedicine strategy that can be effective for the treatment of oral squamous cell carcinoma. The present work might be of great importance to the further exploration of the potential application of PLGA/NR7 in the clinically relevant animal models.

No MeSH data available.


Related in: MedlinePlus