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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) Fluorescence (left) and optically merged (right) images of SCC7 cells treated with Cy5.5 labeled FPc NPs. (B) In vivo NIRF images of SCC7 tumor-bearing mouse before and after tail vein injection of Cy5.5 labeled FPc NPs (100 μL of 1mg/mL FPc NPs). Imaging time points after injection are indicated.
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Figure 5: (A) Fluorescence (left) and optically merged (right) images of SCC7 cells treated with Cy5.5 labeled FPc NPs. (B) In vivo NIRF images of SCC7 tumor-bearing mouse before and after tail vein injection of Cy5.5 labeled FPc NPs (100 μL of 1mg/mL FPc NPs). Imaging time points after injection are indicated.

Mentions: The above advantageous photothermal effect prompted us to explore the possible utility of FPc NPs as a PTT agent. First, the tumor targeting behavior was examined in cells and in vivo. For monitoring by fluorescence imaging, the GC amines on the nanoparticle surface were labeled with Cy5.5 since its absorption and fluorescence are located in the tissue-penetrating near-infrared (NIR) spectral window 1 ,2. Figure 5A demonstrates the in vitro potential of FPc NPs to target live cancer cells. When FPc NPs were incubated with SCC7 (squamous cell carcinoma) cells for 1 h, clear NIR fluorescence (NIRF) signals were observed from the intracellular regions. This indicates that FPc NPs are cell membrane-permeable to attain intracellular accumulation, which is a prerequisite condition for efficient hyperthermia of cancer cells. More importantly, FPc NPs also presented the efficient tumor targeting capability in vivo. Figure 5B shows noninvasive visualization of the pharmacokinetic behavior: FPc NPs were systemically administered into SCC7 tumor-bearing mice via tail vein injection and the NIRF images were taken with the eXplore Optix system at selected time points after intravenous injection. Immediately after injection (10 min), FPc NPs displayed strong NIRF signal throughout the injected body. This implies good blood circulation of the Pluronic-based nanoparticles with minimal RES filtration in liver or spleen, presumably due to the antifouling surface nature arising from the PEG segment. It is noted that a marked image contrast was only seen at the tumor. Importantly, the tumor signal was further increased in the course of time, while the whole-body signal was gradually decreased: at 6 h post-injection, FPc NPs were mainly taken up by the tumor so as to readily identify the tumor location. This behavior indicates significant tumor accumulation of the blood-circulating Pluronic nanoparticles thanks to the size-motivated EPR effect. All the imaging results conclude that the photothermal FPc NPs have great tumor targetability in vitro as well as in vivo, suggesting the possible utility in PTT application.


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) Fluorescence (left) and optically merged (right) images of SCC7 cells treated with Cy5.5 labeled FPc NPs. (B) In vivo NIRF images of SCC7 tumor-bearing mouse before and after tail vein injection of Cy5.5 labeled FPc NPs (100 μL of 1mg/mL FPc NPs). Imaging time points after injection are indicated.
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Related In: Results  -  Collection

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Figure 5: (A) Fluorescence (left) and optically merged (right) images of SCC7 cells treated with Cy5.5 labeled FPc NPs. (B) In vivo NIRF images of SCC7 tumor-bearing mouse before and after tail vein injection of Cy5.5 labeled FPc NPs (100 μL of 1mg/mL FPc NPs). Imaging time points after injection are indicated.
Mentions: The above advantageous photothermal effect prompted us to explore the possible utility of FPc NPs as a PTT agent. First, the tumor targeting behavior was examined in cells and in vivo. For monitoring by fluorescence imaging, the GC amines on the nanoparticle surface were labeled with Cy5.5 since its absorption and fluorescence are located in the tissue-penetrating near-infrared (NIR) spectral window 1 ,2. Figure 5A demonstrates the in vitro potential of FPc NPs to target live cancer cells. When FPc NPs were incubated with SCC7 (squamous cell carcinoma) cells for 1 h, clear NIR fluorescence (NIRF) signals were observed from the intracellular regions. This indicates that FPc NPs are cell membrane-permeable to attain intracellular accumulation, which is a prerequisite condition for efficient hyperthermia of cancer cells. More importantly, FPc NPs also presented the efficient tumor targeting capability in vivo. Figure 5B shows noninvasive visualization of the pharmacokinetic behavior: FPc NPs were systemically administered into SCC7 tumor-bearing mice via tail vein injection and the NIRF images were taken with the eXplore Optix system at selected time points after intravenous injection. Immediately after injection (10 min), FPc NPs displayed strong NIRF signal throughout the injected body. This implies good blood circulation of the Pluronic-based nanoparticles with minimal RES filtration in liver or spleen, presumably due to the antifouling surface nature arising from the PEG segment. It is noted that a marked image contrast was only seen at the tumor. Importantly, the tumor signal was further increased in the course of time, while the whole-body signal was gradually decreased: at 6 h post-injection, FPc NPs were mainly taken up by the tumor so as to readily identify the tumor location. This behavior indicates significant tumor accumulation of the blood-circulating Pluronic nanoparticles thanks to the size-motivated EPR effect. All the imaging results conclude that the photothermal FPc NPs have great tumor targetability in vitro as well as in vivo, suggesting the possible utility in PTT application.

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