Abstract
This study combined two novel nanomedicines, a novel LCP Pyro PA photodynamic therapy (PDT) and LCP EGFR siRNA gene therapy, to treat head and neck cancer. A novel photosensitizer, pyropheophorbide phosphatydic acids (Pyro PA), was first modified into Lipid-Calcium phosphate nanoparticles named LCP Pyro PA NPs, and targeted with aminoethylanisamide as a novel PDT photosensitizer. EGFR siRNA was encapsulated into LCP NPs to silence EGFR expression. Measured sizes of LCP EGFR siRNA NPs and LCP Pyro-PA NPs were 34.9 ± 3.0 and 20 nm respectively, and their zeta potentials were 51.8 ± 1.8 and 52.0 ± 7.6 mV respectively. In vitro studies showed that EGFR siRNA was effectively knocked down after photodynamic therapy (PDT) with significant inhibition of cancer growth. SCC4 or SAS xenografted nude mice were used to verify therapeutic efficacy. The LCP Control siRNA+PDT group of SCC4 and SAS showed significantly reduced tumor volume compared to the phosphate buffered saline (PBS) group. In the LCP-EGFR siRNA+LCP Pyro PA without light group and LCP EGFR siRNA + PBS with light group, SCC4 and SAS tumor volumes were reduced by ~140% and ~150%, respectively, compared to the PBS group. The LCP EGFR siRNA+PDT group of SCC4 and SAS tumor volumes were reduced by ~205% and ~220%, respectively, compared to the PBS group. Combined therapy showed significant tumor volume reduction compared to PBS, control siRNA, or PDT alone. QPCR results showed EGFR expression was significantly reduced after treatment with EGFR siRNA with PDT in SCC4 and SAS compared to control siRNA or PDT alone. Western blot results confirmed decreased EGFR protein expression in the combined therapy group. No toxic results were found in serum biomarkers. No inflammatory factors were found in heart, liver and kidney tissues. Results suggest that the novel LCP Pyro PA mediated PDT combined with LCP siEGFR NPs could be developed in clinical modalities for treating human head and neck cancer in the future.
Highlights
Head and neck cancers develop mainly in the human oral cavity [1], larynx, hypopharynx and sinonasal areas
Ninety-five percent of head and neck cancer is caused by squamous cell carcinoma (SCC) [2]
The goal of this study was to investigate the therapeutic outcome of photosensitizer, pyropheophorbide phosphatydic acids (Pyro PA) (LCP Pyro PA NPs mediated photodynamic therapy (PDT)), with LCP NPs with EG
Summary
Head and neck cancers develop mainly in the human oral cavity [1], larynx, hypopharynx and sinonasal areas. Ninety-five percent of head and neck cancer is caused by squamous cell carcinoma (SCC) [2]. Clinical practices to treat human head and neck cancers include surgery, chemotherapy. Pharmaceutics 2021, 13, 1435 carcinogenesis [2]. Clinical practices to treat human head and neck cancers incl surgery, chemotherapy and radiotherapy. Another new modality is photodyna therapy (PDT), a noninvasive alternative for oral cancer therapy with proven cumulative side effects after repeated therapies, including little to no observed scarrin the oral cavity [3,4]. PDT uses a specific photosensitizer activated by a specific l wavelength that selectively kills cancerous cells [5]. We are the first to deve and radiotherapy
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