Cationic Porphyrin-Based Ionic Nanomedicines for Improved Photodynamic Therapy

Abstract

This study presents the synthesis and characterization of monosubstituted cationic porphyrin as a photodynamic therapeutic agent. Cationic porphyrin was converted into ionic materials by using a single-step ion exchange reaction. The small iodide counteranion was replaced with bulky BETI and IR783 anions to reduce aggregation and enhance the photodynamic effect of porphyrin. Carrier-free ionic nanomedicines were then prepared by using the reprecipitation method. The photophysical characterization of parent porphyrin, ionic materials, and ionic nanomaterials, including absorbance, fluorescence and phosphorescence emission, quantum yield, radiative and nonradiative rate, and lifetimes, was performed. The results revealed that the counteranion significantly affects the photophysical properties of porphyrin. The ionic nanomaterials exhibited an increase in the reactive oxygen yield and enhanced cytotoxicity toward the MCF-7 cancer cell line. Examination of results revealed that the ionic materials exhibited an enhanced photodynamic therapeutic activity with a low IC₅₀ value (nanomolar) in cancerous cells. These nanomedicines were mainly localized in the mitochondria. The improved light cytotoxicity is attributed to the enhanced photophysical properties and positive surface charge of the ionic nanomedicines that facilitate efficient cellular uptake. These results demonstrate that ionic material-based nanodrugs are promising photosensitizers for photodynamic therapy.

Keywords: cancer therapy; cytotoxicity; ionic materials; nanoparticles; organic synthesis; singlet oxygen; subcellular localization.

Figure 1.

(a, c) Absorption spectra and (b, d) fluorescence emission spectra of parent porphyrin and IMs in ethanol and water at an excitation wavelength of 415 nm.

Figure 2.

Photodegradation of (a) DPBF in ethanol, (b) ABDA in water, and (c) ABDA in PBS at 415 nm excitation.

Figure 3.

Cellular uptake of parent porphyrin and INMs after 4, 6, and 8 h of incubation of 15 nmol of drug with MCF-7 cancer cells. Data are presented as the mean SD (n = 3).

Figure 4.

(a) Dark cytotoxicity, (b) light toxicity at 4 h, and (c) light cytotoxicity at 6 h of MCF-7 cells upon dosage with varying concentrations of parent compounds and INMs for 24 and 4 h, respectively (*p < 0.05, **p < 0.01, ***p < 0.005).

Figure 5.

Subcellular localization of 5 μM porphyrin or porphyrin-based ionic nanomedicines on MCF-7 breast cancer cells for 6 h. Scale bar = 10 μm.

Scheme 1.

Synthesis Scheme of 5-(N,N,N-Trimethylanilinium-4-yl)-10,15,20-triphenylporphyrin Iodide

Scheme 2.

Synthesis Scheme of [Porph][IR783] IMs