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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

a Particle size distribution of CDDP-loaded PLGA-PEG-NR7 nanoparticles. b TEM image of PD/IFS
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Fig2: a Particle size distribution of CDDP-loaded PLGA-PEG-NR7 nanoparticles. b TEM image of PD/IFS

Mentions: The CDDP-loaded PLGA NPs were formed by the self-assembly of drug in the hydrophobic core of the polymeric micelles. After being dissolved in DMSO and dialyzed against water, CDDP was able to spontaneously self-assemble into micelles with hydrophobic PLGA core and hydrophilic PEG outer shell. The resulting NPs were expected to be nanometre range. The particle size and size distributions of NP were evaluate by dynamic light scattering technique (DLS). The average size of drug-loaded PLGA NP was around ~100 nm while a slight increment in size was observed for PLGA/NR7 NP (~135 nm) (Fig. 2a). The slight increase in size could be attributed to the presence of NR7 peptide on the surface of the nanoparticles. Nevertheless, both the NP system showed an excellent polydispersity index of PDI ~ 0.15. Despite the increase in the overall size, resulting size was in accordance with literature for cancer drug delivery applications. It has been reported that micelles with an average size between 50- and 150-nm-diameter ranges, could easily avoid rapid renal clearance or leakage through normal vasculature, yet allow EPR-mediated accumulation through tumor-associated leaky vasculature [17, 18].Fig. 2


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 Particle size distribution of CDDP-loaded PLGA-PEG-NR7 nanoparticles. b TEM image of PD/IFS
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig2: a Particle size distribution of CDDP-loaded PLGA-PEG-NR7 nanoparticles. b TEM image of PD/IFS
Mentions: The CDDP-loaded PLGA NPs were formed by the self-assembly of drug in the hydrophobic core of the polymeric micelles. After being dissolved in DMSO and dialyzed against water, CDDP was able to spontaneously self-assemble into micelles with hydrophobic PLGA core and hydrophilic PEG outer shell. The resulting NPs were expected to be nanometre range. The particle size and size distributions of NP were evaluate by dynamic light scattering technique (DLS). The average size of drug-loaded PLGA NP was around ~100 nm while a slight increment in size was observed for PLGA/NR7 NP (~135 nm) (Fig. 2a). The slight increase in size could be attributed to the presence of NR7 peptide on the surface of the nanoparticles. Nevertheless, both the NP system showed an excellent polydispersity index of PDI ~ 0.15. Despite the increase in the overall size, resulting size was in accordance with literature for cancer drug delivery applications. It has been reported that micelles with an average size between 50- and 150-nm-diameter ranges, could easily avoid rapid renal clearance or leakage through normal vasculature, yet allow EPR-mediated accumulation through tumor-associated leaky vasculature [17, 18].Fig. 2

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