PH-responsive nanomedicine co-encapsulated with Erlotinib and chlorin e6 can enable effective treatment of triple negative breast cancer via reprogramming tumor vasculature

Abstract

High expression of epidermal growth factor receptor (EGFR) involved in promoting tumor proliferation, hypoxia, and many others has found to be associated with poor prognosis of diverse cancers including triple negative breast cancer (TNBC). The newest progresses have indicated that anti-EGFR chemotherapy could reinforce various cancer treatments by normalizing the abnormal tumor vasculature to improve tumor oxygenation, but suffers from severe side effects owing to the constitutive expression of EGFR in normal tissues. Herein, we develop a pH-responsive nanomedicine simultaneously loaded of Erlotinib, an inhibitor of EGFR tyrosine kinase, and chlorin e6 (Ce6), a photosensitizer, via the CaCO3-assistant emulsion method. The obtained Erlotinib-Ce6-loaded CaCO3 nanoparticles (ECCaNPs) show pH-responsive release of payloads and efficient tumor accumulation, thus enable the normalization of tumor vasculature to improve intratumoral oxygenation and decrease tumor growth by inhibiting EGFR/extracellular regulated protein kinases (ERK)/ AKT serine/threonine kinase 1 (AKT) axis. ECCaNPs together with light exposure can collectively suppress the growth of TNBC cell-line-derived and patient-derived xenograft mouse models through combined chemo- & photodynamic therapy. This study highlights that anti-EGFR chemotherapy programmed tumor vasculature could thereby enhance the therapeutic efficacy of oxygen-consuming cancer treatments, offering a promising strategy to figure out efficient combination cancer treatments to benefit TNBC patients.