Background Melanoma is an aggressive form of skin cancer, and single-modality treatments often fail to prevent tumor recurrence and metastasis. Combination therapy has emerged as an effective approach to improve treatment outcomes.Methods In this study, we developed a multifunctional nanoplatform, MIL@DOX@ICG, utilizing MIL-101-NH2(Fe) as a carrier to co-deliver the chemotherapeutic agent doxorubicin (DOX) and the photosensitizer indocyanine green (ICG). MIL-101-NH2(Fe) was synthesized via a hydrothermal method. Drug release was evaluated under different pH conditions, and the photothermal effect was tested under near-infrared (NIR) laser irradiation. Hydroxyl radical and reactive oxygen species generation capacities were quantified. Cellular studies using B16F10 cells assessed cytotoxicity, cellular uptake, migration inhibition, and colony formation suppression. In vivo experiments in melanoma-bearing mice evaluated antitumor efficacy and systemic safety through tumor growth inhibition, histological analyses, and toxicity assessments.Results MIL@DOX@ICG exhibited a uniform octahedral structure with a particle size of approximately 139 nm and high drug loading efficiencies for DOX (33.70%) and ICG (30.59%). The nanoplatform demonstrated pH-responsive drug release and potent photothermal effects. The generation of hydroxyl radicals via the Fenton reaction and reactive oxygen species production under NIR laser irradiation by MIL@DOX@ICG were confirmed. In vitro assessments revealed significant cytotoxicity of MIL@DOX@ICG against B16F10 cells under NIR laser irradiation, with improved efficacy in inhibiting cell proliferation and migration. In vivo studies confirmed the superior antitumor efficacy of MIL@DOX@ICG + NIR treatment, synergistically harnessing chemotherapy, photothermal therapy, photodynamic therapy, and chemodynamic therapy effects while maintaining excellent biocompatibility.Conclusion Our findings underscore the potential of MIL-101-NH2(Fe) nanoparticles as a versatile and effective platform for synergistic melanoma therapy, offering a promising strategy for overcoming the limitations of conventional treatment modalities.
Dianfa Zhao,Jie Liu,Yunshan Zhou,Lijuan Zhang,Yuxu Zhong,Yang Yang,Baoquan Zhao,Mengru Yang,Yong’an Wang
It is very important to establish a sustained-release pralidoxime chloride (2-PAM) drug system with brain targeting function for the treatment of neurotoxicant poisoning. Herein, Vitamin B1 (VB1), also known as thiamine, which can specifically bind to the thiamine transporter on the surface of the blood–brain barrier, was incorporated onto the surface of MIL-101-NH2(Fe) nanoparticles with a size of ∼100 nm. Pralidoxime chloride was further loaded within the interior of the above resulted composite by soaking, and a resulting composite drug (denoted as 2-PAM@VB1-MIL-101-NH2(Fe)) with a loading capacity of 14.8% (wt) was obtained. The results showed that the drug release rate of the composite drug was increased in PBS solution with the increase of pH (2–7.4) and a maximum drug release rate of 77.5% at pH 4. Experiments on the treatment of poisoning by gavage with the nerve agent sarin in mice combined with atropine revealed that sustained release of 2-PAM from the composite drug was achieved for more than 72 h. Sustained and stable reactivation of poisoned acetylcholinesterase (AChE) was observed with an enzyme reactivation rate of 42.7% in the ocular blood samples at 72 h. By using both zebrafish brain and mouse brain as models, we found that the composite drug could effectively cross the blood–brain barrier and restore the AChE activity in the brain of poisoned mice. The composite drug is expected to be a stable therapeutic drug with brain targeting and prolonged drug release properties for nerve agent intoxication in the middle and late stages of treatment.
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