Tumour-specific PI3K inhibition via nanoparticle-targeted delivery in head and neck squamous cell carcinoma

Aviram Mizrachi, Yosi Shamay, Janki Shah, Samuel Brook, Joanne Soong, Vinagolu K. Rajasekhar, John L. Humm, John H. Healey, Simon N. Powell, José Baselga, Daniel A. Heller*, Adriana Haimovitz-Friedman, Maurizio Scaltriti

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Alterations in PIK3CA, the gene encoding the p110α subunit of phosphatidylinositol 3-kinase (PI3Kα), are frequent in head and neck squamous cell carcinomas. Inhibitors of PI3Kα show promising activity in various cancer types, but their use is curtailed by dose-limiting side effects such as hyperglycaemia. In the present study, we explore the efficacy, specificity and safety of the targeted delivery of BYL719, a PI3Kα inhibitor currently in clinical development in solid tumours. By encapsulating BYL719 into P-selectin-targeted nanoparticles, we achieve specific accumulation of BYL719 in the tumour milieu. This results in tumour growth inhibition and radiosensitization despite the use of a sevenfold lower dose of BYL719 compared with oral administration. Furthermore, the nanoparticles abrogate acute and chronic metabolic side effects normally observed after BYL719 treatment. These findings offer a novel strategy that could potentially enhance the efficacy of PI3Kα inhibitors while mitigating dose-limiting toxicity in patients with head and neck squamous cell carcinomas.

Original languageEnglish
Article number14292
JournalNature Communications
StatePublished - 13 Feb 2017
Externally publishedYes


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