RESUMEN
In this study, fine hollow nanocapsules, consisting of NiFe hydroxides (denoted as H-NiFe(OH)x), are designed and synthesized for the delivery of an anticancer drug (Doxorubicin, DOX) and tumour depletion. Owing to its fascinating characteristics of "Fe2+ preservation and regeneration", H-NiFe(OH)x presents considerable Fenton activity for hydroxyl radical (ËOH) induction. Efficient delivery of DOX is ensured due to its hollow microstructure, and a typical pH-responsive drug release is enabled. More importantly, the intracellular DOX, in addition to its intrinsic antitumour properties, induces extra exogenous H2O2 which favors the production of ËOH by H-NiFe(OH)x in tumour cells. In consequence, remarkable in vitro and in vivo antitumour properties are successfully achieved. This drug delivery system is particularly inspirational to further studies in the exploration of intelligent therapeutic platforms for combinational tumour therapy.
Asunto(s)
Nanocápsulas , Neoplasias , Doxorrubicina/uso terapéutico , Sistemas de Liberación de Medicamentos , Humanos , Peróxido de Hidrógeno , Hidróxidos , Nanocápsulas/uso terapéutico , Neoplasias/tratamiento farmacológicoRESUMEN
Cellular starvation induced by glucose oxidase (GOx) had been extensively explored as a potential approach for tumor therapy. However, the therapeutic efficacy suffers daunting challenges due to the unsatisfactory intracellular transportation of GOx molecules. Herein for the first time, hydroxide nanoparticles with unique hollow microstructure (denoted as H-NiAl(OH)x) were designed and synthesized for GOx delivery. In this system, despite its intrinsic degradation properties in acidic tumor microenvironment, Ni2+ ions released during degradation may catalyze a Fenton reaction to induce considerable production of cytotoxic hydroxyl radicals (OH). The cavity of hollow nanocapsules provides large surface area, and favors GOx capsulation and delivery. The findings indicate the intracellular glucose can be effectively consumed by GOx transported, and the reaction products consisting of acid and H2O2 facilitate the OH induction of nanocapsules in a synergistic manner. Both in vitro and in vivo antitumor properties have been consequently achieved by H-NiAl(OH)x/GOx systems. This study offering catalytic nanocapsules based on Ni2+ ions may spark a series of follow-on explorations in constructing drug delivery and therapeutic systems for synergistic tumor treatment.
Asunto(s)
Nanocápsulas , Nanopartículas , Glucosa Oxidasa , Peróxido de Hidrógeno , Radical HidroxiloRESUMEN
Developing drug delivery platforms that can modulate a tumor microenvironment and deliver multiple therapeutics to targeted tumors is critical for efficient cancer treatment. Achieving these platforms still remains a great challenge. Herein, biodegradable nanocapsules based on MnFe hydroxides (H-MnFe(OH)x) have been developed as a new type of cargo delivery with high loading capacity and catalytic activity, enabling synergetic therapy with promoted efficacy by relieving hypoxia in tumor tissues. As a proof of concept, a photosensitizer (indocyanine green, ICG) and a chemotherapeutic drug (doxorubicin, DOX) are co-loaded in nanocapsules and selectively released upon degradation of the nanocapsules in the acidic tumor microenvironment, and are promoted by near infrared irradiation. Meanwhile, Mn2+/Fe3+ ions released from the degradation of nanocapsules catalyze the conversion of H2O2 in a tumor microenvironment into oxygen, which modulates tumor hypoxia and dramatically boosts multimodal therapies. Remarkable synergistic anticancer outcomes have been demonstrated both in vitro and in vivo, paving the way towards future multifunctional therapeutic platforms.