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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) Temperature evolution in suspensions of FPc NPs and FIc NPs, free PcBu4 (prepared by dissolving the dried ternary mixture of FPc in toluene), water solution of ICG, and pure water during continuous irradiation of 671 nm laser at 6.4 W/cm2 for 15 min. (B) Image of sample-containing wells before and after laser irradiation.
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Figure 4: (A) Temperature evolution in suspensions of FPc NPs and FIc NPs, free PcBu4 (prepared by dissolving the dried ternary mixture of FPc in toluene), water solution of ICG, and pure water during continuous irradiation of 671 nm laser at 6.4 W/cm2 for 15 min. (B) Image of sample-containing wells before and after laser irradiation.

Mentions: The photothermal heating properties were comparatively evaluated by irradiating dye-aggregated nanoparticles (FPc NPs and FIc NPs) and non-aggregated ICG solution in water with a NIR laser (671 nm, 6.4 W/cm2). We also examined free PcBu4 solution, prepared by dissolution of thermally processed ternary mixture of FPc in toluene, to elucidate the aggregation effect on the photothermal behavior. Figure 4A shows temporal photothermal profiles measured in uncapped open containers, where the concentrations were adjusted so that the optical densities at 671 nm are identical for all the samples for quantitative comparison. Under irradiation, the phthalocyanine-aggregated dispersion (FPc NPs) manifested a two-phase temperature behavior: initial rapid heating above 55 oC and then saturation after 3 min of irradiation. In the latter phase, reflux of water was observed on the container wall, suggesting that boiling occurred in the laser irradiated volume. No photothermal heating effect was observed from laser-transparent pure water without nanoparticles, clearly evidencing that the photon energies absorbed by FPc NPs were efficiently converted to molecular vibration and caused heating of the surrounding medium. In contrast to FPc NPs, other samples (FIc NPs, ICG and free PcBu4) under continuous laser irradiation did not exhibit sustained photothermal heating of the media but rather displayed temperature drops after initial heat generation. The temperature declination after initial heating is attributable to the chemical degradation of cyanine dyes under the condition with intense laser excitation and localized heat generation. To attain the sustained heat generation, thermal robustness as well as photostability might be key considerations because laser irradiation of NIR dyes is known to instantaneously raise the local temperature far above 100 oC 7. As shown in Figure 4B, only FPc NPs retained the blue color of phthalocyanine after 15 min of laser irradiation, whereas the colors of cyanine dyes and even of free PcBu4 were completely bleached under the same condition. The comparison with cyanine-based samples evidences that phthalocyanines are highly stable optically as well as thermally, being a promising alternative to conventional cyanine dyes for the applications requiring intense light illumination. Another important point is that FPc NPs showed the greatly enhanced photostability over free PcBu4. This can be attributed to significant blocking of the oxygen-involved photobleaching process in FPc NPs, because highly aggregated PcBu4 molecules in the nanoparticulate matrix may have a low chance of contact with surrounding oxygen species. Overall, laser-excited FPc NPs generating sufficient heat to induce cellular hyperthermia validate the concept of phthalocyanine nanoaggregation to produce high-performance organic NIR absorbers for PTT.


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) Temperature evolution in suspensions of FPc NPs and FIc NPs, free PcBu4 (prepared by dissolving the dried ternary mixture of FPc in toluene), water solution of ICG, and pure water during continuous irradiation of 671 nm laser at 6.4 W/cm2 for 15 min. (B) Image of sample-containing wells before and after laser irradiation.
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Related In: Results  -  Collection

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Figure 4: (A) Temperature evolution in suspensions of FPc NPs and FIc NPs, free PcBu4 (prepared by dissolving the dried ternary mixture of FPc in toluene), water solution of ICG, and pure water during continuous irradiation of 671 nm laser at 6.4 W/cm2 for 15 min. (B) Image of sample-containing wells before and after laser irradiation.
Mentions: The photothermal heating properties were comparatively evaluated by irradiating dye-aggregated nanoparticles (FPc NPs and FIc NPs) and non-aggregated ICG solution in water with a NIR laser (671 nm, 6.4 W/cm2). We also examined free PcBu4 solution, prepared by dissolution of thermally processed ternary mixture of FPc in toluene, to elucidate the aggregation effect on the photothermal behavior. Figure 4A shows temporal photothermal profiles measured in uncapped open containers, where the concentrations were adjusted so that the optical densities at 671 nm are identical for all the samples for quantitative comparison. Under irradiation, the phthalocyanine-aggregated dispersion (FPc NPs) manifested a two-phase temperature behavior: initial rapid heating above 55 oC and then saturation after 3 min of irradiation. In the latter phase, reflux of water was observed on the container wall, suggesting that boiling occurred in the laser irradiated volume. No photothermal heating effect was observed from laser-transparent pure water without nanoparticles, clearly evidencing that the photon energies absorbed by FPc NPs were efficiently converted to molecular vibration and caused heating of the surrounding medium. In contrast to FPc NPs, other samples (FIc NPs, ICG and free PcBu4) under continuous laser irradiation did not exhibit sustained photothermal heating of the media but rather displayed temperature drops after initial heat generation. The temperature declination after initial heating is attributable to the chemical degradation of cyanine dyes under the condition with intense laser excitation and localized heat generation. To attain the sustained heat generation, thermal robustness as well as photostability might be key considerations because laser irradiation of NIR dyes is known to instantaneously raise the local temperature far above 100 oC 7. As shown in Figure 4B, only FPc NPs retained the blue color of phthalocyanine after 15 min of laser irradiation, whereas the colors of cyanine dyes and even of free PcBu4 were completely bleached under the same condition. The comparison with cyanine-based samples evidences that phthalocyanines are highly stable optically as well as thermally, being a promising alternative to conventional cyanine dyes for the applications requiring intense light illumination. Another important point is that FPc NPs showed the greatly enhanced photostability over free PcBu4. This can be attributed to significant blocking of the oxygen-involved photobleaching process in FPc NPs, because highly aggregated PcBu4 molecules in the nanoparticulate matrix may have a low chance of contact with surrounding oxygen species. Overall, laser-excited FPc NPs generating sufficient heat to induce cellular hyperthermia validate the concept of phthalocyanine nanoaggregation to produce high-performance organic NIR absorbers for PTT.

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