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Phthalocyanine-aggregated polymeric nanoparticles as tumor-homing near-infrared absorbers for photothermal therapy of cancer.

Lim CK, Shin J, Lee YD, Kim J, Oh KS, Yuk SH, Jeong SY, Kwon IC, Kim S - Theranostics (2012)

Bottom Line: Tiny nanoparticles (~ 60 nm, FPc NPs) were prepared by aqueous dispersion of phthalocyanine-aggregated self-assembled nanodomains that were phase-separated from the melt mixture with Pluronic.Under NIR laser irradiation, FPc NPs manifested robust heat generation capability, superior to an individual cyanine dye and cyanine-aggregated nanoparticles.It is shown here that continuous NIR irradiation of the tumor-targeted FPc NPs can cause phototherapeutic effects in vitro and in vivo through excessive local heating, demonstrating potential of phthalocyanine-aggregated nanoparticles as an all-organic NIR nanoabsorber for hyperthermia.

View Article: PubMed Central - PubMed

Affiliation: 1. Center for Theragnosis, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, Korea;

ABSTRACT
Phthalocyanine-aggregated Pluronic nanoparticles were constructed as a novel type of near-infrared (NIR) absorber for photothermal therapy. Tiny nanoparticles (~ 60 nm, FPc NPs) were prepared by aqueous dispersion of phthalocyanine-aggregated self-assembled nanodomains that were phase-separated from the melt mixture with Pluronic. Under NIR laser irradiation, FPc NPs manifested robust heat generation capability, superior to an individual cyanine dye and cyanine-aggregated nanoparticles. Micro- and macroscopic imaging experiments showed that FPc NPs are capable of internalization into live cancer cells as well as tumor accumulation when intravenously administered into living mice. It is shown here that continuous NIR irradiation of the tumor-targeted FPc NPs can cause phototherapeutic effects in vitro and in vivo through excessive local heating, demonstrating potential of phthalocyanine-aggregated nanoparticles as an all-organic NIR nanoabsorber for hyperthermia.

No MeSH data available.


Related in: MedlinePlus

TEM images of FPc NPs (A) and FIc NPs (B). (C) Zeta potential values of bare FPc NPs (1) and sequentially adsorbed nanoparticles with glycol chitosan (2) and heparin (3).
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Figure 2: TEM images of FPc NPs (A) and FIc NPs (B). (C) Zeta potential values of bare FPc NPs (1) and sequentially adsorbed nanoparticles with glycol chitosan (2) and heparin (3).

Mentions: FPc NPs were fabricated by colloidal dispersion of self-assembled aromatic nanodomains in the F-68 matrix. The process involves 1) preparing a ternary mixture of F-68, PcBu4, and polyethylene glycol (PEG, Mn = 400) in a weight ratio of 100:6.25:25, by hot mechanical stirring at 150 oC for 1.5 h, 2) quenching the hot mixture in an ice bath to induce nanoscopically confined self-assembly of PcBu4 by phase separation from the polymer matrix, and 3) subsequently dispersing the self-assembled PcBu4 colloids by adding water to the quenched mixture. During the steps, the PcBu4-aggregated nanodomains were well-separated and stably dispersed in water by the surface stabilization behavior of a polymeric surfactant (F-68). The transmission electron microscopic (TEM) image elucidates that the obtained colloids are spherical nanoparticles with an average diameter of 75 ± 12 nm (Figure 2A), which is appropriate for facile blood circulation and endocytosis of nanomaterials 32-34. For a comparative study on the photothermal effect, control nanoparticles of non-phthalocyanine aggregates (FIc NPs) were formulated with a general cyanine dye (IcMe6). Owing to the low thermal stability of cyanines, hot mechanical mixing was not able to be processed for the phase-separated dye assembly. Instead, the preparation process was modified into solution mixing of IcMe6 with a more hydrophobic Pluronic F-127 and then colloidal dispersion by adding water to the dried mixture, to yield cyanine-aggregated nanoparticles (FIc NPs) with an average size of 52 ± 16 nm (Figure 2B). To improve the tumor targetability of FPc NPs for further biomedical experiments, the colloidal surface was modified with glycol chitosan and heparin by sequential adsorption. Positively charged glycol chitosan was applied as a gluing component that adheres to the particle surface via hydrogen bonding between Pluronic and glycol units, and then attracts polyanionic heparin to the surface by electrostatic attraction 31. Figure 2C shows the zeta potential alteration during the sequential adsorption. The bare FPc NPs exhibited almost neutral surface charge owing to nonionic nature of the hydrophilic PEG segment. However, the zeta potential became positive (12.2 ± 4.8 mV) and then changed into a negative value (-11.6 ± 5.1 mV) by successive addition of cationic glycol chitosan and anionic heparin. This supports the successful coating of FPc NPs with surface absorbents by layer-by-layer adsorption.


Phthalocyanine-aggregated polymeric nanoparticles as tumor-homing near-infrared absorbers for photothermal therapy of cancer.

Lim CK, Shin J, Lee YD, Kim J, Oh KS, Yuk SH, Jeong SY, Kwon IC, Kim S - Theranostics (2012)

TEM images of FPc NPs (A) and FIc NPs (B). (C) Zeta potential values of bare FPc NPs (1) and sequentially adsorbed nanoparticles with glycol chitosan (2) and heparin (3).
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3475215&req=5

Figure 2: TEM images of FPc NPs (A) and FIc NPs (B). (C) Zeta potential values of bare FPc NPs (1) and sequentially adsorbed nanoparticles with glycol chitosan (2) and heparin (3).
Mentions: FPc NPs were fabricated by colloidal dispersion of self-assembled aromatic nanodomains in the F-68 matrix. The process involves 1) preparing a ternary mixture of F-68, PcBu4, and polyethylene glycol (PEG, Mn = 400) in a weight ratio of 100:6.25:25, by hot mechanical stirring at 150 oC for 1.5 h, 2) quenching the hot mixture in an ice bath to induce nanoscopically confined self-assembly of PcBu4 by phase separation from the polymer matrix, and 3) subsequently dispersing the self-assembled PcBu4 colloids by adding water to the quenched mixture. During the steps, the PcBu4-aggregated nanodomains were well-separated and stably dispersed in water by the surface stabilization behavior of a polymeric surfactant (F-68). The transmission electron microscopic (TEM) image elucidates that the obtained colloids are spherical nanoparticles with an average diameter of 75 ± 12 nm (Figure 2A), which is appropriate for facile blood circulation and endocytosis of nanomaterials 32-34. For a comparative study on the photothermal effect, control nanoparticles of non-phthalocyanine aggregates (FIc NPs) were formulated with a general cyanine dye (IcMe6). Owing to the low thermal stability of cyanines, hot mechanical mixing was not able to be processed for the phase-separated dye assembly. Instead, the preparation process was modified into solution mixing of IcMe6 with a more hydrophobic Pluronic F-127 and then colloidal dispersion by adding water to the dried mixture, to yield cyanine-aggregated nanoparticles (FIc NPs) with an average size of 52 ± 16 nm (Figure 2B). To improve the tumor targetability of FPc NPs for further biomedical experiments, the colloidal surface was modified with glycol chitosan and heparin by sequential adsorption. Positively charged glycol chitosan was applied as a gluing component that adheres to the particle surface via hydrogen bonding between Pluronic and glycol units, and then attracts polyanionic heparin to the surface by electrostatic attraction 31. Figure 2C shows the zeta potential alteration during the sequential adsorption. The bare FPc NPs exhibited almost neutral surface charge owing to nonionic nature of the hydrophilic PEG segment. However, the zeta potential became positive (12.2 ± 4.8 mV) and then changed into a negative value (-11.6 ± 5.1 mV) by successive addition of cationic glycol chitosan and anionic heparin. This supports the successful coating of FPc NPs with surface absorbents by layer-by-layer adsorption.

Bottom Line: Tiny nanoparticles (~ 60 nm, FPc NPs) were prepared by aqueous dispersion of phthalocyanine-aggregated self-assembled nanodomains that were phase-separated from the melt mixture with Pluronic.Under NIR laser irradiation, FPc NPs manifested robust heat generation capability, superior to an individual cyanine dye and cyanine-aggregated nanoparticles.It is shown here that continuous NIR irradiation of the tumor-targeted FPc NPs can cause phototherapeutic effects in vitro and in vivo through excessive local heating, demonstrating potential of phthalocyanine-aggregated nanoparticles as an all-organic NIR nanoabsorber for hyperthermia.

View Article: PubMed Central - PubMed

Affiliation: 1. Center for Theragnosis, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, Korea;

ABSTRACT
Phthalocyanine-aggregated Pluronic nanoparticles were constructed as a novel type of near-infrared (NIR) absorber for photothermal therapy. Tiny nanoparticles (~ 60 nm, FPc NPs) were prepared by aqueous dispersion of phthalocyanine-aggregated self-assembled nanodomains that were phase-separated from the melt mixture with Pluronic. Under NIR laser irradiation, FPc NPs manifested robust heat generation capability, superior to an individual cyanine dye and cyanine-aggregated nanoparticles. Micro- and macroscopic imaging experiments showed that FPc NPs are capable of internalization into live cancer cells as well as tumor accumulation when intravenously administered into living mice. It is shown here that continuous NIR irradiation of the tumor-targeted FPc NPs can cause phototherapeutic effects in vitro and in vivo through excessive local heating, demonstrating potential of phthalocyanine-aggregated nanoparticles as an all-organic NIR nanoabsorber for hyperthermia.

No MeSH data available.


Related in: MedlinePlus