RESUMEN
BACKGROUND: Chemotherapy, the mainstay treatment for metastatic cancer, presents serious side effects due to off-target exposure. In addition to the negative impact on patients' quality of life, side effects limit the dose that can be administered and thus the efficacy of the drug. Encapsulation of chemotherapeutic drugs in nanocarriers is a promising strategy to mitigate these issues. However, avoiding premature drug release from the nanocarriers and selectively targeting the tumour remains a challenge. RESULTS: In this study, we present a pioneering method for drug integration into nanoparticles known as mesoporous organosilica drugs (MODs), a distinctive variant of periodic mesoporous organosilica nanoparticles (PMOs) in which the drug is an inherent component of the silica nanoparticle structure. This groundbreaking approach involves the chemical modification of drugs to produce bis-organosilane prodrugs, which act as silica precursors for MOD synthesis. Mitoxantrone (MTO), a drug used to treat metastatic breast cancer, was selected for the development of MTO@MOD nanomedicines, which demonstrated a significant reduction in breast cancer cell viability. Several MODs with different amounts of MTO were synthesised and found to be efficient nanoplatforms for the sustained delivery of MTO after biodegradation. In addition, Fe3O4 NPs were incorporated into the MODs to generate magnetic MODs to actively target the tumour and further enhance drug efficacy. Importantly, magnetic MTO@MODs underwent a Fenton reaction, which increased cancer cell death twofold compared to non-magnetic MODs. CONCLUSIONS: A new PMO-based material, MOD nanomedicines, was synthesised using the chemotherapeutic drug MTO as a silica precursor. MTO@MOD nanomedicines demonstrated their efficacy in significantly reducing the viability of breast cancer cells. In addition, we incorporated Fe3O4 into MODs to generate magnetic MODs for active tumour targeting and enhanced drug efficacy by ROS generation. These findings pave the way for the designing of silica-based multitherapeutic nanomedicines for cancer treatment with improved drug delivery, reduced side effects and enhanced efficacy.
Asunto(s)
Antineoplásicos , Neoplasias de la Mama , Supervivencia Celular , Mitoxantrona , Compuestos de Organosilicio , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Supervivencia Celular/efectos de los fármacos , Compuestos de Organosilicio/química , Compuestos de Organosilicio/farmacología , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Mitoxantrona/farmacología , Mitoxantrona/química , Mitoxantrona/uso terapéutico , Línea Celular Tumoral , Portadores de Fármacos/química , Dióxido de Silicio/química , Porosidad , Liberación de Fármacos , Nanopartículas/química , Células MCF-7 , Nanomedicina/métodos , Especies Reactivas de Oxígeno/metabolismoRESUMEN
The gene and drug co-delivery system has become one of the primary strategies to overcome cancers. Here, we designed a multifunctional magnetic co-delivery system for nasopharyngeal carcinoma-targeted therapy and MR imaging. Aldehyde sodium alginate (ASA) was used to decorate the oxide iron and load cisplain through coordinate bond to form a core complex. The polymer shell poly(l-lysine)-methoxy-polyethylene glycol-folate was used to coat the core complex through electric interaction to give this nano-medicine a target ability. And this polymer could also give the nano-medicine abilities to adhere and protect DNA, and enhance its solubleness in water. After being transfected with this nano-medicine, the plasmids which contain cancer suppressor gene TFPI2 could enter and express in HNE-1 cells. It caused a higher death and apoptosis rate, inhibited nasopharyngeal carcinoma cells' migration and cloning by the synergic effect together with cisplain. Besides, clear images of this nano-medicine could be got under T2 MR imaging. This magnetic co-delivery system demonstrates a potential as a powerful multifunctional vector for drug delivery and gene vector applications in nasopharyngeal carcinoma.
Asunto(s)
Carcinoma/diagnóstico por imagen , Carcinoma/terapia , Ácido Fólico/farmacocinética , Terapia Genética/métodos , Imagen por Resonancia Magnética/métodos , Nanopartículas de Magnetita/química , Neoplasias Nasofaríngeas/diagnóstico por imagen , Neoplasias Nasofaríngeas/terapia , Polietilenglicoles/química , Polilisina/análogos & derivados , Carcinoma/metabolismo , Línea Celular Tumoral , Materiales Biocompatibles Revestidos/síntesis química , Medios de Contraste/administración & dosificación , Ácido Fólico/química , Humanos , Terapia Molecular Dirigida/métodos , Nanocápsulas/administración & dosificación , Nanocápsulas/química , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/metabolismo , Plásmidos/administración & dosificación , Plásmidos/química , Polilisina/química , Nanomedicina Teranóstica/métodos , Resultado del TratamientoRESUMEN
Aim To establish a modified method of tissue digestion and cis-platin concentration measurement in tissue by atomic absorption spectrometry.Methods Using shimadzu atomic absorption spectrometry system and under the conditions of AA-6300 atomic absorption spectrophotometer,GFA-Ex7i graphite furnace,ASC-6100 automatic sampler and platinum hollow cathode discharge lamp,the cisplatin concentration of the tissues containing loading cisplatin magnetic nanomedicine which were digested with nitric acid and hydrogen peroxide in water bath,was measured by atomic absorption spectrophotometer at 265.9 nm.Results The concentrations of cis-platin in different tissues were in the linear range of 54~283.5 ?g?L-1;all the correlation coefficient were larger than 0.999 and all the inter-day and intro-day variation coefficient were smaller than 5%.Conclusion The modified method of tissue digestion and atomic absorption spectrometry applied is of high precision and efficiency, suitable for the pharmacokinetic research on cis-platin.