Enhanced Efficacy of Gefitinib in Drug‐Sensitive and Drug‐Resistant Cancer Cell Lines after Arming with a Singlet Oxygen Releasing Moiety

Abstract

Attractive results have been achieved with small‐molecule target‐based drugs in the anticancer field; however, enhancing their treatment effect and solving the problem of drug resistance remain key concerns worldwide. Inspired by the specific affinity of gefitinib for tumour cells and the strong oxidation capacity of singlet oxygen, we combined a chemically generated singlet oxygen moiety with the small‐molecule targeted drug gefitinib to improve its anticancer effect. We designed and synthesised a novel compound (Y5‐1), in which a small‐molecule targeted therapy agent (gefitinib) and a singlet oxygen (provided by an in vitro photodynamic reaction) thermally controlled releasing moiety are covalently conjugated. We demonstrated that the introduction of the singlet oxygen thermally controlled releasing moiety enhanced the anticancer activities of gefitinib. The results of this study are expected to provide a novel strategy to enhance the effect of chemotherapy drugs on drug‐resistant cell lines.

Construction of a pH-responsive nanoreactor and its specific inhibition of oral squamous cell carcinoma growth via TME and xCT/GSH/GPX4 axis

“…47 Moreover, the current chemotherapy drugs suffer from poor selectivity, signi cant side effects, and a propensity to develop drug resistance. [48][49][50][51] Hence, there is an urgent need to develop novel drugs with distinct mechanisms of action to address the challenges associated with existing treatment modalities.…”

Chemodynamic Therapy Combined with Multifunctional Nanomaterials and Their Applications in Tumor Treatment

“…Cisplatin chemotherapy [10] is often used for cancer and is a promising tumor treatment strategy. However, the long-term use of cisplatin [11] can also lead to drug resistance, [12] thereby severely impeding its therapeutic effectiveness and clinical transformation, showing a phenomenon of "drug-resistance". Due to the complexities of the biological barrier in vivo, [13] the present nano-drug delivery system [14] for cancer treatment still has obvious disadvantages such as poor tumor aggregation [15] and low efficacy.…”