RESUMO
Combining photodynamic therapy (PDT), chemodynamic therapy (CDT), and ferroptosis is a valuable means for an enhanced anticancer effect. However, traditional combination of PDT/CDT/ferroptosis faces several hurdles, including excess glutathione (GSH) neutralization and preparation complexity. In this work, a versatile multifunctional nanoparticle (HCNP) self-assembled from two porphyrin molecules, chlorin e6 and hemin, is developed. The as-constructed HCNPs exhibit a peroxidase-mimic catalytic activity, which can lead to the in situ generation of endogenous O2, thereby enhancing the efficacy of PDT. Furthermore, the generation of hydroxyl radicals (â¢OH) in the tumor environment in reaction to the high level of H2O2 and the simultaneous disruption of intracellular GSH endow the HCNPs with the capacity of enhanced CDT, resulting in a more effective therapeutic outcome in combination with PDT. More importantly, GSH depletion further leads to the inactivation of GSH peroxide 4 and induced ferroptosis. Both in vitro and in vivo results showed that the combination of PDT/CDT/ferroptosis realizes highest antitumor efficacy significantly under laser irradiation. Therefore, by integrating the superiorities of O2 and â¢OH generation capacity, GSH-depletion effect, and bioimaging into a single nanosystem, the HCNPs are a promising single therapeutic agent for tumor PDT/CDT/ferroptosis combination therapy.
Assuntos
Antineoplásicos/uso terapêutico , Hemina/uso terapêutico , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/uso terapêutico , Animais , Antineoplásicos/química , Antineoplásicos/efeitos da radiação , Catálise , Linhagem Celular Tumoral , Clorofilídeos , Feminino , Ferroptose/efeitos dos fármacos , Glutationa/metabolismo , Hemina/química , Hemina/efeitos da radiação , Células Endoteliais da Veia Umbilical Humana , Humanos , Radical Hidroxila/metabolismo , Luz , Camundongos Endogâmicos BALB C , Nanopartículas/química , Nanopartículas/efeitos da radiação , Oxigênio/metabolismo , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/efeitos da radiação , Porfirinas/química , Porfirinas/efeitos da radiaçãoRESUMO
Due to the traditional therapies of cancer inducing huge pains to patients, the non-invasive photo-guided therapies are attracting massive attentions of researchers. Herein, the intelligent-designed carbon-dots/hemin nanoplatforms (HCDs NPs) were developed, owning high-authority photo-therapy for cancer. The fluorescence resonance energy transfer (FRET) effect enhanced the photo-thermal ability of HCDs NPs, endowing the synthesized nanoplatforms with photo-dynamic property simultaneously. Therefore, the obtained HCDs NPs could achieve synergetic photo-thermal and photo-dynamic therapies for cancer. Basing on the experimental results, the prepared HCDs NPs could induce the temperature enhancement high to ca 26⯰C under laser irradiation, also with the outstanding photo-dynamic efficacy. More than 90% of cancer cells die after 10â¯min laser treatment. Thus, the dual-modal photo-therapeutic HCDs NPs are promising and excellent nanomaterials for potential application in synergistic cancer therapy.
Assuntos
Antineoplásicos/farmacologia , Hemina/farmacologia , Pontos Quânticos/química , Antineoplásicos/efeitos da radiação , Antineoplásicos/toxicidade , Carbono/química , Carbono/efeitos da radiação , Carbono/toxicidade , Transferência Ressonante de Energia de Fluorescência , Hemina/efeitos da radiação , Hemina/toxicidade , Células Hep G2 , Humanos , Hipertermia Induzida , Luz , Tamanho da Partícula , Fotoquimioterapia , Pontos Quânticos/efeitos da radiação , Pontos Quânticos/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Solubilidade , TemperaturaRESUMO
The chemiluminescent oxidation of luminol by hydrogen peroxide in the presence of hemin is revisited in an UV-C cross-linked PVP hydrogel. Chemiluminescence properties such as initial light intensity (I(0)), area of emission (S) and observed rate constants (k(obs)) are studied, varying the concentration of all reactants using a multivariate factorial approach.