Cisplatin combined with laser‑activated nanotherapy as an adjuvant therapy for head and neck cancer

Abstract

Head and neck cancers (HNCs), in general, have a poor prognosis with a worldwide 5-year survival rate of <50%. Numerous HNC patients with locoregionally advanced, difficult-to-treat, inoperable, recurrent and drug-resistant tumors may require additional treatment options when the standard of care surgery, chemotherapy and radiation are not viable. The poor outcomes justify exploring strategies to increase the efficacy of lower doses of drugs, such as cisplatin, by combining these drugs with other treatment modalities and manipulating the dosing schedule. Cisplatin is a standard and effective anticancer drug; however, some patients cannot tolerate the side-effects or exhibit drug resistance. Adjuvant therapies may lower the effective dose, decrease side-effects, address drug resistance and improve overall survival outcomes, particularly for patients with difficult-to-treat tumors. The present study focuses on combining cisplatin with laser-activated nanotherapy (LANT), as an adjuvant HNC therapy, with the aim of enhancing the therapeutic efficacy of lower doses of cisplatin and decreasing treatment times. The results demonstrate the potential of cisplatin and LANT co-therapy as a possible addition to the adjuvant therapy options for HNC using 3 cell lines: Detroit 562, FaDu and CAL 27 cells. Combining cisplatin with LANT demonstrated up to a 5.4-fold greater therapeutic efficacy than with cisplatin monotreatment. The most effective combination in the present study was 1 µM Cis + 5 nM LANT, which demonstrated cell death comparable to 5.9, 4.2 and 5.3 µM of Cis monotreatment, in Detroit 562, FaDu and CAL 27 cells, respectively. This result suggests that a lower cisplatin dose may be combined with LANT to achieve the same therapeutic efficacy as that obtained with higher doses of cisplatin monotreatment. The combination of LANT and cisplatin suggests that LANT may enhance the therapeutic efficiency of low doses of cisplatin, decrease treatment times and improve patient outcomes.

Assessment of a Nano-Docetaxel Combined Treatment for Head and Neck Cancer

“…According to our previously established methods, the LMM regression post hoc test compared the means of the six DTX and LANT monotreatments versus combination treatment groups for all three HNSCC cell lines [42]. These post hoc analyses are summarized in Table 3, showing statistically significant differences (p < 0.05) in the means for most of the comparison groups.…”

“…The in vitro effects of LANT as a monotreatment (percentage of cell death, dose-response curves, and half-maximal effective concentrations (EC50) of 8.1, 11.0, and 6.7 nM) were previously established for Detroit 562, FaDu, and CAL 27, respectively [41,42]. In summary, 4 min NIR laser excitation of AuNRs at six concentrations (0, 5, 10, 15, 20, and 25 nM) demonstrates AuNR concentration-dependent cell death (Figure 2).…”

“…HNSCC cells were treated with the combination of DTX and LANT according to the methods used in our previous study [42], adapted as follows: HNSCC cell lines were seeded in 96-well plates at 1 × 10 4 cells/well and allowed to adhere overnight. The cell number was the same as that for DTX monotreatment.…”

Assessment of a Nano-Docetaxel Combined Treatment for Head and Neck Cancer

“…The in vitro effects of LANT as a monotreatment (percentage of cell death, dose-response curves, and half-maximal effective concentrations (EC50) of 8.1 nM, 11.0 nM, and 6.7 nM) were previously established for Detroit 562, FaDu, and CAL 27, respectively [37,39]. In summary, 4 min NIR laser excitation of AuNRs at six concentrations (0, 5, 10, 15, 20, and 25 nM) demonstrates AuNR concentrationdependent cell death [Figure 2].…”

Unlocking the Potential of Ru(II) Dual‐action Compounds with the Power of the Heavy‐atom Effect†

“…While Ru(II) compounds have shown promise as lightactivated therapeutics, their utility is currently limited by several factors. First and foremost, most ruthenium complexes show EC 50 (effective concentration required to kill 50% of the cells) values in the low micromolar range, similar to cisplatin (34)(35)(36). While Ru(II) complexes rarely break the micromolar to nanomolar barrier, there are many organic cancer drugs already approved by the FDA approved that are cytotoxic at nanomolar concentrations.…”