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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.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.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.

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

The cytotoxicity potential of free CDDP, PLGA NP, and PLGA/NR7 NP were evaluated by Live/Dead assay. Cells were stained with a live/dead cell viability assay (Invitrogen). This assay uses two fluorescent probes, calcein AM and ethidium homodimer-1
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Fig6: The cytotoxicity potential of free CDDP, PLGA NP, and PLGA/NR7 NP were evaluated by Live/Dead assay. Cells were stained with a live/dead cell viability assay (Invitrogen). This assay uses two fluorescent probes, calcein AM and ethidium homodimer-1

Mentions: The cytotoxicity assay was further confirmed by Live/Dead assay. The cells were treated with respective formulations and then incubated with Calcein AM and Ethidium bromide dye as representative live and dead cell markers. As seen from Fig. 6, higher extent of red fluorescence (68 %) was observed for the cells exposed with PLGA/NR7 than compared with non-targeted PLGA NP (39 %). Consistent with cytotoxicity assay, free CDDP showed 40 % more viable cells (green fluorescence) and the red fluorescence was significantly decreased. Whereas extent of red and green fluorescence is an indication of dead cells and live cells, respectively. Despite the cytotoxic effect of PLGA/NR7 carrier, slight presence of green cells suggest that drug release from the nanoparticle in a sustained manner and therefore kills in a time-dependent manner. Generally, Calcein AM can easily enter cells by diffusion and it is converted to Calcein by the intracellular esterase which stains the live cells green. The damaged or dead cells are stained red with Ethidium bromide.Fig. 6


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)

The cytotoxicity potential of free CDDP, PLGA NP, and PLGA/NR7 NP were evaluated by Live/Dead assay. Cells were stained with a live/dead cell viability assay (Invitrogen). This assay uses two fluorescent probes, calcein AM and ethidium homodimer-1
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig6: The cytotoxicity potential of free CDDP, PLGA NP, and PLGA/NR7 NP were evaluated by Live/Dead assay. Cells were stained with a live/dead cell viability assay (Invitrogen). This assay uses two fluorescent probes, calcein AM and ethidium homodimer-1
Mentions: The cytotoxicity assay was further confirmed by Live/Dead assay. The cells were treated with respective formulations and then incubated with Calcein AM and Ethidium bromide dye as representative live and dead cell markers. As seen from Fig. 6, higher extent of red fluorescence (68 %) was observed for the cells exposed with PLGA/NR7 than compared with non-targeted PLGA NP (39 %). Consistent with cytotoxicity assay, free CDDP showed 40 % more viable cells (green fluorescence) and the red fluorescence was significantly decreased. Whereas extent of red and green fluorescence is an indication of dead cells and live cells, respectively. Despite the cytotoxic effect of PLGA/NR7 carrier, slight presence of green cells suggest that drug release from the nanoparticle in a sustained manner and therefore kills in a time-dependent manner. Generally, Calcein AM can easily enter cells by diffusion and it is converted to Calcein by the intracellular esterase which stains the live cells green. The damaged or dead cells are stained red with Ethidium bromide.Fig. 6

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.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.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.

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