Department of Chemistry, University of Arkansas at Little Rock, 2801 South University Avenue, Little Rock, Arkansas 72204, United States.
Department of Biology, University of Arkansas at Little Rock, 2801 South University Avenue, Little Rock, Arkansas 72204, United States.
ACS Appl Bio Mater. 2021 Oct 18;4(10):7708-7718. doi: 10.1021/acsabm.1c00961. Epub 2021 Sep 24.
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.
在此,提出了一种经济高效、快速的方法来开发基于离子材料的组合纳米药物用于癌症治疗。通过一步离子交换反应将化疗药物(膦)阳离子和光动力治疗药物(卟啉)阴离子结合在一起。然后,通过简单的再沉淀策略,从这种基于离子材料的组合药物中制备纳米药物。在存在化疗抗衡阳离子的情况下,观察到卟啉的光物理特性得到改善,例如非辐射速率常数变慢、磷光发射增强、寿命延长以及吸收光谱的红移。通过使用两种探针测量单线态氧量子产率来研究纳米药物的光动力治疗活性。与母体卟啉化合物相比,由于在大体积化疗离子存在下抑制卟啉单元的面对面聚集,合成的组合材料的活性氧物种量子产率增加了 2 倍。与相应的母体化合物相比,组合治疗纳米药物在 MCF-7(癌性乳腺)细胞系中的暗毒性也增加了。这是由于与游离药物相比,组合纳米药物的细胞摄取率更高。此外,通过用叶酸对纳米药物进行功能化,然后与 MCF-7 和 MCF-10A(非癌性乳腺)孵育,获得了对癌细胞的选择性毒性。光毒性实验表明,与两种母体药物相比,合成的离子纳米药物由于光物理性质的改善和有效的组合效应而导致细胞死亡更多。这种简单经济的策略可以很容易地用于未来开发具有改善光动力的其他许多组合离子纳米药物。