Abstract
Negative or positive HPV-associated Head and Neck Squamous Cell Carcinomas (HNSCCs) are high recurrence neoplasms usually resulting in a poor prognosis, mainly due to metastasis formation. Despite the low overall patient survival rate and the severe side effects, the treatment of choice is still cisplatin-based chemotherapy. Here, we report a straightforward protocol for the production of high throughput 3D models of negative or positive HPV-associated HNSCCs, together with their employment in the therapeutic evaluation of gold ultrasmall-in-nano architectures comprising an endogenously-activatable cisplatin prodrug. Beyond enhancing the biosafety of cisplatin, our approach paves the way for the establishment of synergistic co-therapies for HNSCCs based on excretable noble metals.
Highlights
Head and Neck Squamous Cell Carcinoma (HNSCC) is a complex group of malignancies that affect different body sites, among which the oral cavity, nasopharynx, oropharynx, larynx, and salivary glands
Single or combined cisplatin-based therapies are the principal treatments for HNSCCs neoplasms and their sensitivity is similar for ±Human PapillomaVirus (HPV)-associated conditions, even if their sub-optimal efficacy is limited by associated severe systemic toxicities, such as nephrotoxicity, neurotoxicity, ototoxicity, and emesis [11]
We employed NAs internally-labelled with Alexa Fluor-647 (NAs-647) or internally-loaded with a cisplatin prodrug (NAs-cisPt) to investigate, respectively, the internalization behaviors and the cytotoxicity trends in 2D and 3D SCC-25 and UPCI:SCC-154
Summary
Head and Neck Squamous Cell Carcinoma (HNSCC) is a complex group of malignancies that affect different body sites, among which the oral cavity, nasopharynx, oropharynx, larynx, and salivary glands. Single or combined cisplatin-based therapies are the principal treatments for HNSCCs neoplasms and their sensitivity is similar for ±HPV-associated conditions, even if their sub-optimal efficacy is limited by associated severe systemic toxicities, such as nephrotoxicity, neurotoxicity, ototoxicity, and emesis [11] In this context, Pt(IV) complexes provide an attractive alternative to Pt(II) compounds because. Tumor spheroids represent the best option for the study of nanoparticles efficacy, since they are composed of different populations of quiescent/necrotic and proliferative cells, comprising gradients of nutrients and oxygen and at the same time are cheap and easy to handle [32] They allow for obtaining reliable information on the efficiency of nanomaterials and internalization mechanisms, taking into account cell–cell and cell–extracellular matrix (ECM) interactions [33,34]. Our findings are a significant step forward toward the translation of novel and efficient noble metal-based co-treatments for patients
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