Abstract
Encapsulating cisplatin (CDDP) into liposomes to form lipid-platinum-chloride nanoparticles (LPC NPs) has shown a promising anticancer effect in melanoma, bladder, and liver cancer models. This promising anticancer effect of LPC NPs challenges us to study its implications in combination with photodynamic therapy (PDT). Herein, we report the therapeutic efficacy of PDT+LPC on a xenograft model of oral squamous cell carcinoma (OSCC). Results showed that PDT+LPC significantly reduced the tumor volume by up to ~112%. Meanwhile, LPC, PDT+CDDP, or the CDDP group showed ~98.8%, ~73.1%, or ~39.5% volume reductions, respectively. Histological examination suggests that PDT+LPC or LPC treatment showed minimal side effects on renal damage compared to either CDDP or the PDT+CDDP group. Immunohistochemistry staining (IHC) staining on Ki-67, CD31, cleaved caspase-3, TUNEL assays, and western blots of tumor suppressor p53 confirmed consistent results. Most importantly, PDT+LPC prolonged tumor growth inhibition, which leads to minimum chemotherapy treatment administrations. Results suggest that PDT cytotoxicity provided a potent additive effect towards chemotherapy efficacy. Therefore, combined PDT with LPC NPs enhanced the therapeutic outcome in human OSCC.
Highlights
Cisplatin is known to promote DNA interstrand crosslinks to hinder cellular processes such as replication, transcription, and up-regulation of the tumor suppressor gene of p53
We aimed to investigate the therapeutic efficacy of photodynamic therapy (PDT)+LPC in inhibiting tumor growth in a xenograft oral squamous cell carcinoma (OSCC) mouse model
We found that PDT+LPC or the LPC group alone significantly reduced (p < 0.001) the tumor volume by to 25.7% and 39.7% compared to the PDT+CDDP group, respectively
Summary
Cisplatin is known to promote DNA interstrand crosslinks to hinder cellular processes such as replication, transcription, and up-regulation of the tumor suppressor gene of p53. The cytotoxicity of cisplatin triggers cell cycle arrest at the G2 phase, leading to tumor cell apoptosis and cell death [1,2]. Due to this potent cytotoxicity, cisplatin remains the frontline chemotherapeutic agent in various cancer types [3,4,5]. PDT is known to transiently increase blood vessel permeability, in turn increasing the nanoparticle uptake inside the tumor via a mechanism known as super-enhanced permeability and retention (SUPR) [14,15]
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