Improved Photophysical Properties of Ionic Material-Based Combination Chemo/PDT Nanomedicine

Abstract

Herein, a cost-effective and prompt approach to develop ionic material-based combination nanodrugs for cancer therapy is presented. A chemotherapeutic (phosphonium) cation and photodynamic therapeutic (porphyrin) anion are combined using a single step ion exchange reaction. Afterward, a nanomedicine is prepared from this ionic materials-based combination drug using a simplistic strategy of reprecipitation. Improved photophysical characteristics such as a slower nonradiative rate constant, an enhanced phosphorescence emission, a longer lifetime, and a bathochromic shift in absorbance spectra of porphyrin are observed in the presence of a chemotherapeutic countercation. The photodynamic therapeutic activity of nanomedicines is investigated by measuring the singlet oxygen quantum yield using two probes. As compared to the parent porphyrin compound, the synthesized combination material showed a 2-fold increase in the reactive oxygen species quantum yield, due to inhibition of face-to-face aggregation of porphyrin units in the presence of bulky chemotherapeutic ions. The dark cytotoxicity of combination therapy nanomedicines in the MCF-7 (cancerous breast) cell line is also increased as compared to their corresponding parent compounds in vitro. This is due to the high cellular uptake of the combination nanomedicines as compared to that of the free drug. Further, selective toxicity toward cancer cells was acquired by functionalizing nanomedicine with folic acid followed by incubation with MCF-7 and MCF-10A (noncancerous breast). Light toxicity experiments indicate that the synthesized ionic nanomedicine shows a greater cell death than either parent drug due to the improved photophysical properties and effective combination effect. This facile and economical strategy can easily be utilized in the future to develop many other combination ionic nanomedicines with improved photodynamics.

Keywords: cytotoxicity; ionic liquids; ionic materials; photodynamic therapy; porphyrin.

Figure 1.

Scheme of the IMs combination drug synthesis.

Figure 2.

(a) Absorption spectra and (b) fluorescence emission spectra of 2.5 μM dye samples/INMs in water and in ethanol at an excitation wavelength maximum for each sample of approximately 420 nm.

Figure 3.

Photodegradation of (a) DPBF and (b) ABDA upon increasing irradiation time in the presence of TCPP, [P₆₆₆₁₄]₄[TCPP], and MB. The final drug concentrations were 5 and 10 μM with DPBF and ABDA, respectively.

Figure 4.

Cell viability of (a) MCF-7 cells upon dosage with varying concentrations of combination INMs and parent compounds (0.5–20 μM) for 24 h and (b) FA-coated INMs incubated in cancer (MCF-7) and noncancerous (MCF-10A) cell lines for 24 h at a concentration range of 0.5–10 μM (*p < 0.05, **p < 0.01, ***p < 0.005).

Figure 5.

Toxicity of (a) TCPP and (b) [P₆₆₆₁₄]₄[TCPP] INMs after 4 h of incubation in MCF-7 cells under light irradiation, 0.14 W/cm² (+), or in the dark (−) at a concentration range of 0.5–20 μM (*p < 0.05, **p < 0.01, ***p < 0.005).

Figure 6.

Cellular uptake of TCPP and INMs in MCF-7 cells after incubation of 4 nmol of drug for 4 h.