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Abstract: Treatment of biologically complex diseases, such as cancer, can significantly benefit from combination therapies. These powerful therapies are able to simultaneously target different biological targets, thereby overcoming or reducing drug resistance, decreasing dose-related toxicity, and potentially exhibiting synergistic effects. Herein, we combine the effects of nitric oxide (NO) gas therapy and an anticancer drug Doxorubicin (Dox) using a porous organic polymer (POP) as a delivery vehicle for both. SH-POP, synthesized by a facile, room-temperature method, is rich in both thiol (-SH) and secondary amine (R-NH-R’) functional groups, which can be post-synthetically nitrosylated in a room-temperature reaction that uses water as a solvent, yielding SNO-POP. Fourier-transform infrared (FT-IR) and Raman spectroscopy confirm that both types of functional groups are nitrosylated. Upon white light irradiation, SNO-POP releases up to ~60 µmol of NO per g, and exhibits reversible switch on – switch off NO release behavior triggered by simple light irradiation for at least 20 cycles. Unlike many conventional systems, where a known small-molecule NO donor is incorporated into the pores, here, the porous polymer itself serves as a NO donor, so the pores remain available for the encapsulation of another therapeutic, i.e. Dox. The release of Dox from the Dox@SNO-POP system is pH-sensitive and occurs preferentially in a slightly acidic environment (pH = 5.4). HeLa cancer cell viability studies confirm an enhancement in toxicity that can be ascribed to the synergistic effects of light-triggered NO release and pH-triggered Dox release. Confocal microscopy imaging reveals the presence of both species inside cells. This study is expected to stimulate the development of porous polymers as potent vehicles for combination therapies in cancer treatment and beyond.
Keywords: porous organic polymer, nitric oxide, combination therapy, synergistic therapy, chemotherapy
Published in RUNG: 05.07.2024; Views: 88; Downloads: 0
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