Novel nanoliposomes for targeted codelivery of three anticancer agents against head and neck squamous cell carcinoma

Maryam Mohammadi, Fahimeh Bagheri Tofighi, Maedeh Vakili Saatloo, Mehdi Talebi, Maryam Kouhsoltani, Hamed Hamishehkar

Abstract


Background and purpose: Head and neck squamous cell carcinoma (HNSCC) is a malignant tumor in which the overexpression of epidermal growth factor receptor (EGFR) is associated with malignancy. For the treatment of HNSCC, cetuximab (CIT) as an anti-EGFR antibody is prescribed in combination with anticancer chemotherapy drugs for greater effectiveness.

Experimental approach: In this work, a CIT-targeted immunoliposome loaded with cisplatin (CP) and docetaxel (DTX) was developed to allow co-administration of the antibody and the anticancer chemotherapy drugs and selective delivery to HNSCC cells. Developed immunoliposomes were characterized for particle sizes, PDI, zeta potential, surface morphologies, and encapsulation efficiency. Moreover, additional in vitro studies were conducted, including cytotoxicity against HN5 cell line, and cellular uptake studies. 

Findings/Results: The final targeted liposomes exhibited an average diameter of 68.65 ± 3.4 nm; PDI and zeta-potential were respectively around -7.9 ± 1.7 mV and 0.35 ± 0.05. The encapsulation efficacy of DTX and CP within the immunoliposomes was approximately 95 ± 4% and 85 ± 4%, respectively. Flow cytometric analysis revealed that the cellular uptake rate of final immunoliposomes was significantly higher than that of the naked liposomes, indicating that CT conjugation on the surface of nanoliposomes facilitated higher accumulation via receptor-mediated endocytosis. Moreover, co-encapsulation of CP and DTX into CIT-immunoliposomes increased the apoptosis by 24.06% compared to single-drug nanoformulations.

Conclusions and implications: The results indicated that nanoliposomes anchored with CIT enhanced drug accumulation and cytotoxicity in cancer cells and reduced the likelihood of adverse side effects, paving the way for more effective cancer therapies.

 


Keywords


Cisplatin; Docetaxel; Head and neck squamous cell carcinoma; Immunoliposomes; Targeted drug delivery.

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References


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