Although sorafenib, a multi-kinase inhibitor, has provided
noteworthy
benefits in patients with hepatocellular carcinoma (HCC), the inevitable
side effects, narrow therapeutic window, and low bioavailability seriously
affect its clinical application. To be clinically distinctive, innovative
drugs must meet the needs of reaching tumor tissues and cause limited
side effects to normal organs and tissues. Recently, photodynamic
therapy, utilizing a combination of a photosensitizer and light irradiation,
was selectively accumulated at the tumor site and taken up effectively
via inducing apoptosis or necrosis of cancer cells. In this study,
a nano-chemo-phototherapy drug was fabricated to compose an iridium-based
photosensitizer combined with sorafenib (IPS) via a self-assembly
process. Compared to the free iridium photosensitizer or sorafenib,
the IPS exhibited significantly improved therapeutic efficacy against
tumor cells because of the increased cellular uptake and the subsequent
simultaneous release of sorafenib and generation of reactive oxygen species production
upon 532 nm laser irradiation. To evaluate the effect of synergistic
treatment, cytotoxicity detection, live/dead staining, cell proliferative
and apoptotic assay, and Western blot were performed. The IPS exhibited
sufficient biocompatibility by hemolysis and serum biochemical tests.
Also, the results suggested that IPS significantly inhibited HCC cell
proliferation and promoted cell apoptosis. More importantly, marked
anti-tumor growth effects via inhibiting cell proliferation and promoting
tumor cell death were observed in an orthotopic xenograft HCC model.
Therefore, our newly proposed nanotheranostic agent for combined chemotherapeutic
and photodynamic therapy notably improves the therapeutic effect of
sorafenib and has the potential to be a new alternative option for
HCC treatment.
Hepatocellular carcinoma (HCC) accounts for the predominant form of liver malignancy and presents a leading cause of cancer-related death globally. Sorafenib (SOR), a first-line targeted drug for advanced HCC treatment, has a battery of untoward side effects. Photothermal therapy (PTT) has been utilized as an effective adjuvant in synergy with other approaches. However, little is known about the tumoricidal efficacy of combining SOR with PTT for HCC. Herein, a novel versatile nanoparticle, Cu2−xSe@SOR@PEG (CSP), that is based on a photothermal Cu2−xSe core and SOR for simultaneously reinforcing PTT and reducing the adverse effects of SOR was constructed. The synthesized CSP exhibited a remarkably enhanced therapeutic effect upon 808 nm laser irradiation via dampening HCC cell propagation and metastasis and propelling cell apoptosis. The intravenous administration of CSP substantially suppressed tumor growth in a xenograft tumor mouse model. It was noted that the CSP manifested low toxicity and excellent biocompatibility. Together, this work indicates a promising and versatile tool that is based on synergistic PTT and molecular-targeted therapy for HCC management.
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