RESUMEN
Esophageal squamous cell carcinoma (ESCC) remains a major health challenge, with cisplatin (CDDP) being the primary chemotherapy drug, albeit accompanied by resistance development over time. This study introduces a novel platinum drug delivery system, EMLipoPt(IV), tailored to enhance platinum uptake and diminish its inactivation, providing a solution to CDDP resistance in ESCC. By synthesizing a fusion of the ESCC cell membrane with liposomal Pt(IV) prodrugs, we integrated the tumor-targeting capacity of the ESCC membrane with the inactivation resistance of Pt(IV) prodrugs. In vivo and in vitro evaluations illustrated EMLipoPt(IV)'s robustness against inactivating agents, superior tumor-targeting capacity, and remarkable ability to suppress CDDP-resistant tumor progression. Importantly, the biosafety profile of EMLipoPt(IV) surpassed existing treatments, offering a prolonged survival rate in animal models. Collectively, this work not only presents a pioneering approach in ESCC chemotherapy but also provides a blueprint for combating drug resistance in other cancers, emphasizing the broader potential for tailored drug delivery systems.
Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Profármacos , Animales , Cisplatino/farmacología , Cisplatino/uso terapéutico , Platino (Metal)/uso terapéutico , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Profármacos/farmacología , Profármacos/uso terapéutico , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/metabolismo , Resistencia a Antineoplásicos , Línea Celular Tumoral , Membrana Celular/metabolismoRESUMEN
Retinal neovascularization is typically accompanied by hypoxia-induced oxidative injury in the vascular system. This study developed an ultrasmall (6-8 nm) platinum (Pt) nanozyme loaded mitochondria-targeted liposome (Pt@MitoLipo) to alleviate hypoxia and eliminate excess reactive oxygen species (ROS) for effective retinal neovascularization disease therapy. Pt nanozymes possess superoxide dismutase (SOD) and catalase (CAT) cascade enzyme-like activities, which convert cytotoxic O2â¢- and H2O2 into nontoxic H2O and O2. Triphenylphosphonium (TPP)-conjugated liposomes were coated on the surface of Pt nanozymes to increase their biocompatibility and help them penetrate the cell membrane, escape from the lysosomal barrier, and target mitochondria, thus achieving precise scavenging of mitochondrial O2â¢- and relief from hypoxia. Using an oxygen-induced retinopathy (OIR) mouse model, we demonstrated that Pt@MitoLipo nanozymes significantly suppressed hypoxia-induced abnormal neovascularization and facilitated avascular normalization of the retina in vivo without any noticeable toxicity. This study provides a promising way to break through cellular barriers and target scavenging mitochondrial O2â¢- and illustrates the potential of ROS-scavenging and hypoxia relief in retinal neovascularization disease therapy.