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

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.

Keywords: Hyperthermia; Nanoparticles.; Near-infrared photonics; Phototermal therapy; Phthalocyanine; Tumor targeting.

Figure 1

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

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).

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.

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.

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.

Figure 6

(A) Viability of laser-exposed SCC7 cells without (black) or with (red) treatment of FPc NPs as a function of laser irradiation time. The data were collected from MTT assay at 12 h after the laser exposure. The error bars indicate the standard deviations for independent experiments (n=10). (B) Tumor growth (ΔV) of laser-exposed SCC7 tumor-bearing mice with or without (control) intravenous injection of FPc NPs (200 μL of 1 mg mL^-1 FPc NPs). The error bars indicate the standard deviations for independent experiments (n=4).