ABSTRACT
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.
Subject(s)
Antineoplastic Agents/therapeutic use , Hemin/therapeutic use , Nanoparticles/therapeutic use , Neoplasms/drug therapy , Photosensitizing Agents/therapeutic use , Porphyrins/therapeutic use , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/radiation effects , Catalysis , Cell Line, Tumor , Chlorophyllides , Female , Ferroptosis/drug effects , Glutathione/metabolism , Hemin/chemistry , Hemin/radiation effects , Human Umbilical Vein Endothelial Cells , Humans , Hydroxyl Radical/metabolism , Light , Mice, Inbred BALB C , Nanoparticles/chemistry , Nanoparticles/radiation effects , Oxygen/metabolism , Photochemotherapy , Photosensitizing Agents/chemistry , Photosensitizing Agents/radiation effects , Porphyrins/chemistry , Porphyrins/radiation effectsABSTRACT
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.
Subject(s)
Antineoplastic Agents/pharmacology , Hemin/pharmacology , Quantum Dots/chemistry , Antineoplastic Agents/radiation effects , Antineoplastic Agents/toxicity , Carbon/chemistry , Carbon/radiation effects , Carbon/toxicity , Fluorescence Resonance Energy Transfer , Hemin/radiation effects , Hemin/toxicity , Hep G2 Cells , Humans , Hyperthermia, Induced , Light , Particle Size , Photochemotherapy , Quantum Dots/radiation effects , Quantum Dots/toxicity , Reactive Oxygen Species/metabolism , Solubility , TemperatureABSTRACT
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.
