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Gold nanorods/mesoporous silica-based nanocomposite as theranostic agents for targeting near-infrared imaging and photothermal therapy induced with laser.

Liu Y, Xu M, Chen Q, Guan G, Hu W, Zhao X, Qiao M, Hu H, Liang Y, Zhu H, Chen D - Int J Nanomedicine (2015)

Bottom Line: The construction of the nanostructure began with synthesis of GNRs by seed-mediated growth method, followed by the coating of mesoporous silica, the chemical conjugation of PEG and tLyp-1 peptide, and the enclosure of ICG as an NIR imaging agent in the mesoporous.The as-prepared nanoparticles could shield the GNRs against their self-aggregation, improve the stability of ICG, and exhibit negligible dark cytotoxicity.More importantly, such a theranostic nanocomposite could realize the combination of GNRs-based photothermal ablation under NIR illumination, ICG-mediated fluorescent imaging, and tLyp-1-enabled more easy endocytosis into breast cancer cells.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China ; Department of Pharmacy, Bengbu Medical College, Bengbu, People's Republic of China.

ABSTRACT
Photothermal therapy (PTT) is widely regarded as a promising technology for cancer treatment. Gold nanorods (GNRs), as excellent PTT agent candidates, have shown high-performance photothermal conversion ability under laser irradiation, yet two major obstacles to their clinical application are the lack of selective accumulation in the target site following systemic administration and the greatly reduced photothermal conversion efficiency caused by self-aggregating in aqueous environment. Herein, we demonstrate that tLyp-1 peptide-functionalized, indocyanine green (ICG)-containing mesoporous silica-coated GNRs (I-TMSG) possessed dual-function as tumor cells-targeting near-infrared (NIR) fluorescent probe and PTT agents. The construction of the nanostructure began with synthesis of GNRs by seed-mediated growth method, followed by the coating of mesoporous silica, the chemical conjugation of PEG and tLyp-1 peptide, and the enclosure of ICG as an NIR imaging agent in the mesoporous. The as-prepared nanoparticles could shield the GNRs against their self-aggregation, improve the stability of ICG, and exhibit negligible dark cytotoxicity. More importantly, such a theranostic nanocomposite could realize the combination of GNRs-based photothermal ablation under NIR illumination, ICG-mediated fluorescent imaging, and tLyp-1-enabled more easy endocytosis into breast cancer cells. All in all, I-TMSG nanoparticles, in our opinion, possessed the strong potential to realize the effective diagnosis and PTT treatment of human mammary cancer.

No MeSH data available.


Related in: MedlinePlus

Confocal laser scanning microscope images of MDA-MB-231 cells incubated with rhodamine-labeled PMSG or TMSG. Blue: Hoechst 33342 and red: rhodamine B.Abbreviations: PMSG, polyethylene glycol-modified mesoporous silica-coated gold nanorods; TMSG, tLyp-1 peptide-functionalized PMSG; h, hours; MDA-MB-231cells, MD Anderson-metastatic breast-231 cells.
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f7-ijn-10-4747: Confocal laser scanning microscope images of MDA-MB-231 cells incubated with rhodamine-labeled PMSG or TMSG. Blue: Hoechst 33342 and red: rhodamine B.Abbreviations: PMSG, polyethylene glycol-modified mesoporous silica-coated gold nanorods; TMSG, tLyp-1 peptide-functionalized PMSG; h, hours; MDA-MB-231cells, MD Anderson-metastatic breast-231 cells.

Mentions: tLyp-1, similar to extensively studied iRGD and RGD, is a tumor-homing peptide first reported in 2012.44 Recently, tLyp-1-conjugated iron oxide nanoparticles,44 PEG-PLA (polyethylene glycol–polylactic acid) nanoparticles,50 and cationic liposomes51 were constructed by different groups and showed robust and selective homing to tumors, penetrating from the blood vessels into the tumor parenchyma. To examine the characteristics of TMSG as a targeting nanoparticle to human breast cancer MDA-MB-231 cells, optical imaging experiments about endocytosis of fluorescent-labeled nanoparticles were performed. As shown in Figure 7, compared with TMSG, PMSG presented the relatively low intracellular nanoparticle concentrations (represented by red fluorescence). Such results were further demonstrated by fluorescence histograms obtained by flow cytometric analysis (Figure 8A). The mean fluorescence intensity of intracellular TMSG was 1.44-fold higher than that of PMSG (P<0.001, n=3). These results illustrated that TMSG, as a targeting nanomaterial, although contained sterically hindered PEG chains wrapped around the nanoparticles, still shows quite high endocytosis rate, and such phenomenon indicated that there might have been direct crosstalking between tLyp-1-decorated nanoparticles and the corresponding cell surface receptor. To test this hypothesis, we further explored the endocytic pathway of TMSG through coincubating the cancer cells with different competitive or uncompetitive endocytosis inhibitors. As shown in Figure 8B, preincubation with chlorpromazine (clathrin-mediated endocytosis inhibitor), methyl-β-cyclodextrin (lipid raft inhibitor), and free tLyp-1 peptides (competitive inhibitor) significantly decreased the internalization of TMSG by 26.9% (P<0.001), 18.7% (P<0.05), and 30.4% (P<0.001), respectively. Such results indicated that the cellular uptake of TMSG in MDA-MB-231 cells was a clathrin/lipid raft-mediated endocytosis. In addition, preincubating tLyp-1 peptide, which might have occupied the same regions of neuropilin protein (the ligand of tLyp-1 peptide) on cell surface, could effectively inhibit TMSG into the cytoplasm, and this further confirmed the important role of tLyp-1 in nanoparticles endocytosis.


Gold nanorods/mesoporous silica-based nanocomposite as theranostic agents for targeting near-infrared imaging and photothermal therapy induced with laser.

Liu Y, Xu M, Chen Q, Guan G, Hu W, Zhao X, Qiao M, Hu H, Liang Y, Zhu H, Chen D - Int J Nanomedicine (2015)

Confocal laser scanning microscope images of MDA-MB-231 cells incubated with rhodamine-labeled PMSG or TMSG. Blue: Hoechst 33342 and red: rhodamine B.Abbreviations: PMSG, polyethylene glycol-modified mesoporous silica-coated gold nanorods; TMSG, tLyp-1 peptide-functionalized PMSG; h, hours; MDA-MB-231cells, MD Anderson-metastatic breast-231 cells.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4524460&req=5

f7-ijn-10-4747: Confocal laser scanning microscope images of MDA-MB-231 cells incubated with rhodamine-labeled PMSG or TMSG. Blue: Hoechst 33342 and red: rhodamine B.Abbreviations: PMSG, polyethylene glycol-modified mesoporous silica-coated gold nanorods; TMSG, tLyp-1 peptide-functionalized PMSG; h, hours; MDA-MB-231cells, MD Anderson-metastatic breast-231 cells.
Mentions: tLyp-1, similar to extensively studied iRGD and RGD, is a tumor-homing peptide first reported in 2012.44 Recently, tLyp-1-conjugated iron oxide nanoparticles,44 PEG-PLA (polyethylene glycol–polylactic acid) nanoparticles,50 and cationic liposomes51 were constructed by different groups and showed robust and selective homing to tumors, penetrating from the blood vessels into the tumor parenchyma. To examine the characteristics of TMSG as a targeting nanoparticle to human breast cancer MDA-MB-231 cells, optical imaging experiments about endocytosis of fluorescent-labeled nanoparticles were performed. As shown in Figure 7, compared with TMSG, PMSG presented the relatively low intracellular nanoparticle concentrations (represented by red fluorescence). Such results were further demonstrated by fluorescence histograms obtained by flow cytometric analysis (Figure 8A). The mean fluorescence intensity of intracellular TMSG was 1.44-fold higher than that of PMSG (P<0.001, n=3). These results illustrated that TMSG, as a targeting nanomaterial, although contained sterically hindered PEG chains wrapped around the nanoparticles, still shows quite high endocytosis rate, and such phenomenon indicated that there might have been direct crosstalking between tLyp-1-decorated nanoparticles and the corresponding cell surface receptor. To test this hypothesis, we further explored the endocytic pathway of TMSG through coincubating the cancer cells with different competitive or uncompetitive endocytosis inhibitors. As shown in Figure 8B, preincubation with chlorpromazine (clathrin-mediated endocytosis inhibitor), methyl-β-cyclodextrin (lipid raft inhibitor), and free tLyp-1 peptides (competitive inhibitor) significantly decreased the internalization of TMSG by 26.9% (P<0.001), 18.7% (P<0.05), and 30.4% (P<0.001), respectively. Such results indicated that the cellular uptake of TMSG in MDA-MB-231 cells was a clathrin/lipid raft-mediated endocytosis. In addition, preincubating tLyp-1 peptide, which might have occupied the same regions of neuropilin protein (the ligand of tLyp-1 peptide) on cell surface, could effectively inhibit TMSG into the cytoplasm, and this further confirmed the important role of tLyp-1 in nanoparticles endocytosis.

Bottom Line: The construction of the nanostructure began with synthesis of GNRs by seed-mediated growth method, followed by the coating of mesoporous silica, the chemical conjugation of PEG and tLyp-1 peptide, and the enclosure of ICG as an NIR imaging agent in the mesoporous.The as-prepared nanoparticles could shield the GNRs against their self-aggregation, improve the stability of ICG, and exhibit negligible dark cytotoxicity.More importantly, such a theranostic nanocomposite could realize the combination of GNRs-based photothermal ablation under NIR illumination, ICG-mediated fluorescent imaging, and tLyp-1-enabled more easy endocytosis into breast cancer cells.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China ; Department of Pharmacy, Bengbu Medical College, Bengbu, People's Republic of China.

ABSTRACT
Photothermal therapy (PTT) is widely regarded as a promising technology for cancer treatment. Gold nanorods (GNRs), as excellent PTT agent candidates, have shown high-performance photothermal conversion ability under laser irradiation, yet two major obstacles to their clinical application are the lack of selective accumulation in the target site following systemic administration and the greatly reduced photothermal conversion efficiency caused by self-aggregating in aqueous environment. Herein, we demonstrate that tLyp-1 peptide-functionalized, indocyanine green (ICG)-containing mesoporous silica-coated GNRs (I-TMSG) possessed dual-function as tumor cells-targeting near-infrared (NIR) fluorescent probe and PTT agents. The construction of the nanostructure began with synthesis of GNRs by seed-mediated growth method, followed by the coating of mesoporous silica, the chemical conjugation of PEG and tLyp-1 peptide, and the enclosure of ICG as an NIR imaging agent in the mesoporous. The as-prepared nanoparticles could shield the GNRs against their self-aggregation, improve the stability of ICG, and exhibit negligible dark cytotoxicity. More importantly, such a theranostic nanocomposite could realize the combination of GNRs-based photothermal ablation under NIR illumination, ICG-mediated fluorescent imaging, and tLyp-1-enabled more easy endocytosis into breast cancer cells. All in all, I-TMSG nanoparticles, in our opinion, possessed the strong potential to realize the effective diagnosis and PTT treatment of human mammary cancer.

No MeSH data available.


Related in: MedlinePlus