Abstract
BackgroundImproving the water solubility of hydrophobic drugs, increasing their accumulation in tumor tissue and allowing their simultaneous action by different pathways are essential issues for a successful chemotherapeutic activity in cancer treatment. Considering potential clinical application in the future, it will be promising to achieve such purposes by developing new biocompatible hybrid nanocarriers with multimodal therapeutic activity.ResultsWe designed and characterised a hybrid nanocarrier based on human serum albumin/chitosan nanoparticles (HSA/chitosan NPs) able to encapsulate free docetaxel (DTX) and doxorubicin-modified gold nanorods (DOXO-GNRs) to simultaneously exploit the complementary chemotherapeutic activities of both antineoplasic compounds together with the plasmonic optical properties of the embedded GNRs for plasmonic-based photothermal therapy (PPTT). DOXO was assembled onto GNR surfaces following a layer-by-layer (LbL) coating strategy, which allowed to partially control its release quasi-independently release regarding DTX under the use of near infrared (NIR)-light laser stimulation of GNRs. In vitro cytotoxicity experiments using triple negative breast MDA-MB-231 cancer cells showed that the developed dual drug encapsulation approach produces a strong synergistic toxic effect to tumoral cells compared to the administration of the combined free drugs; additionally, PPTT enhances the cytostatic efficacy allowing cell toxicities close to 90% after a single low irradiation dose and keeping apoptosis as the main cell death mechanism.ConclusionsThis work demonstrates that by means of a rational design, a single hybrid nanoconstruct can simultaneously supply complementary therapeutic strategies to treat tumors and, in particular, metastatic breast cancers with good results making use of its stimuli-responsiveness as well as its inherent physico-chemical properties.
Highlights
Improving the water solubility of hydrophobic drugs, increasing their accumulation in tumor tissue and allowing their simultaneous action by different pathways are essential issues for a successful chemotherapeutic activity in cancer treatment
In this work, protein-based hybrid nanoparticles encapsulating both DTX and PSS/DOXO-coated GNRs were designed for their potential use as suitable agents for combined plasmonic-based photothermal therapy (PPTT) and dual-chemotherapy in the search of potential more efficient breast cancer treatments
The prepared nanohybrids aimed to exploit the encapsulation capacity and biocompatibility of human serum albumin (HSA) and the photothermal properties of GNRs in order to achieve a controlled and modulable release of DOXO and DTX by means of a near infrared (NIR)-light triggering mechanism, which should help in fitting drugs dosage and DOXO/DTX ratio delivered, as demonstrated
Summary
Improving the water solubility of hydrophobic drugs, increasing their accumulation in tumor tissue and allowing their simultaneous action by different pathways are essential issues for a successful chemotherapeutic activity in cancer treatment. Considering potential clinical application in the future, it will be promising to achieve such purposes by developing new biocompatible hybrid nanocarriers with multimodal therapeutic activity. Doxorubicin (DOXO) is the most widely antineoplasic drug of choice in first-line therapeutic treatments of metastatic breast cancers. Villar‐Alvarez et al J Nanobiotechnol (2019) 17:106 the generation of inhibitors against apoptotic stimuli or by the activation of multidrug resistant (MDR) genes, which decrease drug uptake and increase its efflux out of malignant cells. This alters the target or metabolic pathway of the antineoplasic compound and activates DNA repair functions in malignant cells [4]. The growth of most tumors is sustained by small populations of “tumor initiating cells” (TICs), which have a high proliferation potential and are inherently resistant, resulting in additional tumor progression and/or recurrence [5]
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