Abstract
Breast cancer (BC) is the most frequently diagnosed cancer with a low survival rate and one of the major causes of cancer-related death. Methotrexate (MTX) is an anti-tumor drug used in the treatment of BC. Poor dispersion in water and toxic side effects limit its clinical application. Gold nanoparticles (AuNPs), owing to their specific structures and unique biological and physiochemical properties, have emerged as potential vehicles for tumor targeting, bioimaging and cancer therapy. An innovative nano drug-loading system (Au @PDA-PEG-MTX NPs) was prepared for targeted treatment of BC. Au @PDA-PEG-MTX NPs under near infra-red region (NIR) irradiation showed effective photothermal therapy against MDA-MB-231 human BC cells growth in vitro by inducing apoptosis through triggering reactive oxygen species (ROS) overproduction and generating excessive heat. In vivo studies revealed deep penetration ability of Au @PDA-PEG-MTX NPs under NIR irradiation to find application in cancer-targeted fluorescence imaging, and exhibited effective photothermal therapy against BC xenograft growth by inducing apoptosis. Histopathological analysis, cellular uptake, cytotoxicity assay, and apoptosis experiments indicated that Au @PDA-PEG-MTX NPs possessed a good therapeutic effect with high biocompatibility and fewer side effects. This Au NPs drug-loading system achieved specific targeting of MTX to BC cells by surface functionalisation, fluorescence imaging under laser irradiation, combined photothermal-chemotherapy, and pH- and NIR- triggered hierarchical drug release.
Highlights
Breast cancer (BC) is one of the most frequent malignancy in women, and is associated with a high mortality rate and economic burden [1, 2]
Reagents The following chemicals were used without further purification and purchased from commercial sources as follows: chloroauric acid (99.95%) from Innochem (Beijing, China); dopamine hydrochloride, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDCI), N-hydroxy succinimide (NHS) and dimethyl sulfoxide (DMSO) from Sigma-Aldrich (St Louis, MO, USA); and 2ʹ,7ʹ-dichlorofluorescin diacetate (DCFH-DA) from Beyotime Biotechnology (Shanghai, China)
The structure of MTX-PEG was identified by infrared spectroscopy and further characterisation was done after synthesis
Summary
Breast cancer (BC) is one of the most frequent malignancy in women, and is associated with a high mortality rate and economic burden [1, 2]. The main aim is to develop effective therapeutic strategies with low toxicity and high specificity to eliminate tumors in the fight against BC [4]. Targeted NPs designed for cancer treatment can deliver chemotherapeutic drugs to specific cancer cells while reducing the exposure of normal healthy cells; larger doses of drugs can be delivered to the tumor site to achieve therapeutic effects with high targeting and low toxicity [8]. AuNPs are a type of inorganic cargo with versatile surface for multi-functionalization and large surface area-to-volume ratio for drug loading, and possess superior optical properties for bioimaging and even photothermal properties for therapy; toxicity and low biocompatibility of AuNPs are the challenges that cannot be ignored [9]. Optimization of drug delivery can be achieved by adjusting the size and shape of AuNPs [10, 11]; small-sized of AuNPs (15 nm of diameter) can be used to reduce its toxicity attributable to being an inorganic material
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