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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

Absorption (A) and Fluorescence (B) spectra of FPc NPs in methylene chloride (back) and water (red) at the same concentration. (C) Photochemical bleaching of RNO by 1O2 generated upon laser excitation of free chlorine e6 (Ce6) (black) and FPc NPs (red) at 671 nm, represented by the temporal dependence of RNO absorbance at 440 nm (-ln A440) during the irradiation of samples with the same asorbance at 671 nm under the identical photobleaching condition. The lines are linear fits of the absorbance plots.
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Figure 3: Absorption (A) and Fluorescence (B) spectra of FPc NPs in methylene chloride (back) and water (red) at the same concentration. (C) Photochemical bleaching of RNO by 1O2 generated upon laser excitation of free chlorine e6 (Ce6) (black) and FPc NPs (red) at 671 nm, represented by the temporal dependence of RNO absorbance at 440 nm (-ln A440) during the irradiation of samples with the same asorbance at 671 nm under the identical photobleaching condition. The lines are linear fits of the absorbance plots.

Mentions: Figure 3 shows the optical properties of PcBu4-aggregated FPc NPs, compared to those of molecularly dispersed PcBu4. For quantitative comparison, both samples were prepared by dispersing or dissolving the thermally processed ternary mixture of FPc in water or dichloromethane at the same concentration. Free PcBu4 monomer in dichloromethane solution showed spectral fingerprints typical of the phthalocyanine chromophores 35, namely, sharp absorption bands across the visible region (a high-energy Soret transition at 341 nm and multiple low-energy Q bands around 600-700 nm) and strong NIR fluorescence at 707 nm. In sharp contrast, FPc NPs manifested a blunt, structureless absorption spectrum with a significant hypochromic change. The broadened Q bands with an emerging longer-wavelength one at ~750 nm (Figure 3A) are in close accordance to the spectral changes characteristic of dimeric aggregation of phthalocyanines 36, 37 . Moreover, the fluorescence of PcBu4 was completely quenched by the formation of FPc NPs (Figure 3B), as typically observed for the common organic dyes in the concentrated or aggregated state 38. In addition to fluorescence quenching, the intersystem crossing (ISC) pathway of PcBu4 was also blocked by aggregation. It is known that the photoexcited PcBu4 in the molecularly isolated state can generate singlet oxygen (1O2) via ISC with the 1O2 generation quantum yield (ΦΔ) of 0.27 39. The photoproduct, 1O2, is one of reactive oxygen species (ROS) and can induce oxidative damage. However, the 1O2 generation capability of PcBu4 was significantly depressed by its incorporation into nanoparticles at a high loading concentration (ΦΔ = 0.04), as spectrally examined by the chemical oxidation of p-nitroso-N,N'-dimethylaniline (RNO) (Figure 3C). All these manifestations evidently indicate that the crystalline PcBu4 molecules (Tm > 300 oC) with the propensity of self-aggregation are highly aggregated inside the nanoparticulate space at the given loading content. The intraparticle aggregation can offer an optimal condition for the thermal conversion of photon energy into heat because it promotes internal conversion and vibrational relaxation of the excited state of dyes and thus efficiently blocks other competitive deactivation pathways (fluorescence decay and ISC) 40. It is noted that absorption and fluorescence spectra of the FPc solution obtained by dissolving the thermally processed ternary mixture are identical to those of a pure PcBu4 solution without thermal treatment, evidencing that the thermally stable phthalocyanine molecules were intact without degradation during the hot mixing process (at 150 oC for 1.5 h).


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)

Absorption (A) and Fluorescence (B) spectra of FPc NPs in methylene chloride (back) and water (red) at the same concentration. (C) Photochemical bleaching of RNO by 1O2 generated upon laser excitation of free chlorine e6 (Ce6) (black) and FPc NPs (red) at 671 nm, represented by the temporal dependence of RNO absorbance at 440 nm (-ln A440) during the irradiation of samples with the same asorbance at 671 nm under the identical photobleaching condition. The lines are linear fits of the absorbance plots.
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Related In: Results  -  Collection

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Figure 3: Absorption (A) and Fluorescence (B) spectra of FPc NPs in methylene chloride (back) and water (red) at the same concentration. (C) Photochemical bleaching of RNO by 1O2 generated upon laser excitation of free chlorine e6 (Ce6) (black) and FPc NPs (red) at 671 nm, represented by the temporal dependence of RNO absorbance at 440 nm (-ln A440) during the irradiation of samples with the same asorbance at 671 nm under the identical photobleaching condition. The lines are linear fits of the absorbance plots.
Mentions: Figure 3 shows the optical properties of PcBu4-aggregated FPc NPs, compared to those of molecularly dispersed PcBu4. For quantitative comparison, both samples were prepared by dispersing or dissolving the thermally processed ternary mixture of FPc in water or dichloromethane at the same concentration. Free PcBu4 monomer in dichloromethane solution showed spectral fingerprints typical of the phthalocyanine chromophores 35, namely, sharp absorption bands across the visible region (a high-energy Soret transition at 341 nm and multiple low-energy Q bands around 600-700 nm) and strong NIR fluorescence at 707 nm. In sharp contrast, FPc NPs manifested a blunt, structureless absorption spectrum with a significant hypochromic change. The broadened Q bands with an emerging longer-wavelength one at ~750 nm (Figure 3A) are in close accordance to the spectral changes characteristic of dimeric aggregation of phthalocyanines 36, 37 . Moreover, the fluorescence of PcBu4 was completely quenched by the formation of FPc NPs (Figure 3B), as typically observed for the common organic dyes in the concentrated or aggregated state 38. In addition to fluorescence quenching, the intersystem crossing (ISC) pathway of PcBu4 was also blocked by aggregation. It is known that the photoexcited PcBu4 in the molecularly isolated state can generate singlet oxygen (1O2) via ISC with the 1O2 generation quantum yield (ΦΔ) of 0.27 39. The photoproduct, 1O2, is one of reactive oxygen species (ROS) and can induce oxidative damage. However, the 1O2 generation capability of PcBu4 was significantly depressed by its incorporation into nanoparticles at a high loading concentration (ΦΔ = 0.04), as spectrally examined by the chemical oxidation of p-nitroso-N,N'-dimethylaniline (RNO) (Figure 3C). All these manifestations evidently indicate that the crystalline PcBu4 molecules (Tm > 300 oC) with the propensity of self-aggregation are highly aggregated inside the nanoparticulate space at the given loading content. The intraparticle aggregation can offer an optimal condition for the thermal conversion of photon energy into heat because it promotes internal conversion and vibrational relaxation of the excited state of dyes and thus efficiently blocks other competitive deactivation pathways (fluorescence decay and ISC) 40. It is noted that absorption and fluorescence spectra of the FPc solution obtained by dissolving the thermally processed ternary mixture are identical to those of a pure PcBu4 solution without thermal treatment, evidencing that the thermally stable phthalocyanine molecules were intact without degradation during the hot mixing process (at 150 oC for 1.5 h).

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