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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

(A) Chemical structures of PcBu4, IcMe6, and ICG. (B) Schematic representation of FPc NP.
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Figure 1: (A) Chemical structures of PcBu4, IcMe6, and ICG. (B) Schematic representation of FPc NP.

Mentions: With these considerations in mind, we have constructed a new composite nanoformulation that is concentrated with photostable NIR dyes inside and surrounded with biocompatible polymer chains on the surface. As shown in Figure 1, the designed structure of dye-aggregated composite nanoparticles (FPc NPs) is based on the physical assembly of all organic constituents, i.e., tetra-t-butylphthalocyanine (PcBu4) as a concentrated hydrophobic NIR dye and Pluronic F-68 as a biocompatible polymer surfactant, as well as glycol chitosan and heparin as particle surface adsorbents. Phthalocyanines are one of the most stable and tinctorially strongest chromophores having absorption in the NIR 25. Owing to the outstanding optical and thermal stability compared to cyanines, they have widely been exploited as a photothermal-mode optical recording medium in a form of aggregated thin films 26. Consequently, it is anticipated that Pluronic nanoparticles concentrated with a hydrophobic phthalocyanine will construct a dye-aggregated inner domain with favorable properties for the PTT activity in terms of NIR absorptivity, photothermal conversion efficiency, and stability. The hydrophilic polyethylene glycol (PEG) surface of the Pluronic-based nanoparticles is known to help prolonged blood circulation and hence EPR-effected tumor accumulation by reducing opsonization in the reticuloendothelial systems (RES) 27, as well as cellular uptake of nanoparticles through enhanced endocytosis 28, 29. In addition, heparin on the particle surface can enhance the in vivo tumor targeting efficiency due to its specific interaction with a fibrinogen-derived product found in the solid tumor 30, 31. Taken together, the designed nanoformulation is expected to offer an optimal platform for the enhanced therapeutic efficacy of PTT. In this study, we report the efficient tumor targeting behavior of FPc NPs in vivo, along with their robust photostability and photothermal effect superior to an individual dye molecule, indocyanine green (ICG) as well as the control nanoparticles concentrated with a general hydrophobic cyanine dye, 1,1',3,3,3',3'-hexamethylindotricar­bocyanine iodide (IcMe6, Figure 1). Through this phthalocyanine-aggregated nanocomposite approach, we demonstrate potential use of all-organic NIR nanoabsorbers for photothermal therapy of cancer in cells and in vivo.


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)

(A) Chemical structures of PcBu4, IcMe6, and ICG. (B) Schematic representation of FPc NP.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: (A) Chemical structures of PcBu4, IcMe6, and ICG. (B) Schematic representation of FPc NP.
Mentions: With these considerations in mind, we have constructed a new composite nanoformulation that is concentrated with photostable NIR dyes inside and surrounded with biocompatible polymer chains on the surface. As shown in Figure 1, the designed structure of dye-aggregated composite nanoparticles (FPc NPs) is based on the physical assembly of all organic constituents, i.e., tetra-t-butylphthalocyanine (PcBu4) as a concentrated hydrophobic NIR dye and Pluronic F-68 as a biocompatible polymer surfactant, as well as glycol chitosan and heparin as particle surface adsorbents. Phthalocyanines are one of the most stable and tinctorially strongest chromophores having absorption in the NIR 25. Owing to the outstanding optical and thermal stability compared to cyanines, they have widely been exploited as a photothermal-mode optical recording medium in a form of aggregated thin films 26. Consequently, it is anticipated that Pluronic nanoparticles concentrated with a hydrophobic phthalocyanine will construct a dye-aggregated inner domain with favorable properties for the PTT activity in terms of NIR absorptivity, photothermal conversion efficiency, and stability. The hydrophilic polyethylene glycol (PEG) surface of the Pluronic-based nanoparticles is known to help prolonged blood circulation and hence EPR-effected tumor accumulation by reducing opsonization in the reticuloendothelial systems (RES) 27, as well as cellular uptake of nanoparticles through enhanced endocytosis 28, 29. In addition, heparin on the particle surface can enhance the in vivo tumor targeting efficiency due to its specific interaction with a fibrinogen-derived product found in the solid tumor 30, 31. Taken together, the designed nanoformulation is expected to offer an optimal platform for the enhanced therapeutic efficacy of PTT. In this study, we report the efficient tumor targeting behavior of FPc NPs in vivo, along with their robust photostability and photothermal effect superior to an individual dye molecule, indocyanine green (ICG) as well as the control nanoparticles concentrated with a general hydrophobic cyanine dye, 1,1',3,3,3',3'-hexamethylindotricar­bocyanine iodide (IcMe6, Figure 1). Through this phthalocyanine-aggregated nanocomposite approach, we demonstrate potential use of all-organic NIR nanoabsorbers for photothermal therapy of cancer in cells and in vivo.

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