Abstract
The synergetic effect of chemoradiotherapy achievement is encouraging but significantly hampered by the prevalence of hypoxia, leading to drug/radiation resistance in solid tumours. To address the problem and improve the efficiency of cancer therapy, a lamellar-structure multifunctional graphene oxide (GO) drug-delivery system with an average size of 243 nm, co-delivering of metronidazole (MI), 5-fluorouracil (5-FU) and FePt magnetic nanoparticles (MNPs), was successfully designed and synthesized in the study. The integration of hypoxic drug carrier loading radiosensitizers and chemotherapeutic drugs simultaneously, combines the properties of hypoxia-sensitivity and chemoradiotherapy co-enhancement within a single nanoplatform, which is expected to provide new ideas for cancer treatment. Through in vitro tests, the hypoxia-sensitivity and cytotoxicity of intracellular reactive oxygen species (ROS) of the nanocomposites (NCs) were proved. Moreover, the additive effect between MI, 5-FU and FePt MNPs in cytotoxicity and radiation sensitization aspects is disclosed. It performs an enhanced cell proliferation inhibition and makes up a self-amplified radiotherapy enhancement system that improves radiation efficiency and cell radiosensitivity simultaneously. In conclusion, the study recommended a novel and promising multifunctional nanoplatform which performed a self-amplified effect that activated chemoradiotherapy co-enhancement.
Highlights
Cancer, as one of the most devastating diseases, is attracting mounting attention [1,2,3]
graphene oxide (GO) was modified by MI and PEG through an EDC chemistry [16,31,45] and designated as GO-MI NCs
The FePt magnetic nanoparticles (MNPs) were prepared by a chemical co-reduction method described in our previous work [7,13,36]
Summary
As one of the most devastating diseases, is attracting mounting attention [1,2,3]. The limitations of radiotherapy and chemotherapy, the most common approaches for cancer treatment in clinics, make the single therapeutic effect far from satisfactory [4,5]. High dose output is required to completely eliminate tumours, due to the low fraction of radiation energy deposition. The high dose, damages normal tissues simultaneously [6]. Oxygen deficiency, a prominent feature of solid tumours [4,8], leads to drug/radiation resistance [9,10,11] which exacerbates the current situation as well. The idea of developing a hypoxic drug-delivery system loading anti-cancer agent and radiosensitizers simultaneously [12] to improve the efficiency of tumour chemoradiotherapy is popular with researchers [13,14]
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