Abstract
The lack of efficient targeting strategies poses significant limitations on the effectiveness of chemotherapeutic treatments. This issue also affects drug-loaded nanocarriers, reducing nanoparticles cancer cell uptake. We report on the fabrication and in vitro characterization of doxorubicin-loaded magnetic liposomes for localized treatment of liver malignancies. Colloidal stability, superparamagnetic behavior and efficient drug loading of our formulation were demonstrated. The application of an external magnetic field guaranteed enhanced nanocarriers cell uptake under cell medium flow in correspondence of a specific area, as we reported through in vitro investigation. A numerical model was used to validate experimental data of magnetic targeting, proving the possibility of accurately describing the targeting strategy and predict liposomes accumulation under different environmental conditions. Finally, in vitro studies on HepG2 cancer cells confirmed the cytotoxicity of drug-loaded magnetic liposomes, with cell viability reduction of about 50% and 80% after 24 h and 72 h of incubation, respectively. Conversely, plain nanocarriers showed no anti-proliferative effects, confirming the formulation safety. Overall, these results demonstrated significant targeting efficiency and anticancer activity of our nanocarriers and superparamagnetic nanoparticles entrapment could envision the theranostic potential of the formulation. The proposed magnetic targeting study could represent a valid tool for pre-clinical investigation regarding the effectiveness of magnetic drug targeting.
Highlights
Hepatocellular carcinoma (HCC) is the most common liver tumor occurring in human beings
The purpose of this work was to tackle the main issue that was encountered in systemic administration of chemotherapies against HCC: without an effective cancer targeting strategy, drugs undergo aspecific and uncontrolled biodistribution that leads to poor anticancer activity with consistent healthy tissue exposure, leading to severe toxic phenomena
We presented a stable, superparamagnetic, and cytotoxic DOX_MagLipo formulation
Summary
Hepatocellular carcinoma (HCC) is the most common liver tumor occurring in human beings It is the sixth most frequent cancer worldwide and the second leading cause of cancer-related death: in 2012 over 700,000 people worldwide died of liver cancer [1,2]. The efficacy of some chemotherapeutic drugs against HCC growth have been proved, severe side effects have been reported, such as proteinuria, skin related toxicities, an increased risk for thromboembolism, and bleeding events [11]. This occurrence has a crucial impact on patient’s quality of life, but, in some cases, impede drug treatment applicability. It is clear how solutions that would improve drug safety and efficacy are of primary clinical interest
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