Research Projects

Oral squamous cell carcinoma (OSCC) is a common malignancy worldwide, with particularly high incidence rates in India and South-East Asia, accounting for 2% of all cancers and significant mortality. Despite advances in treatment, OSCC remains challenging due to its aggressiveness, metastatic potential, and resistance to conventional therapies.1 The tumour microenvironment (TME) of OSCC is a complex and dynamic network comprising cellular, molecular, non-cellular, and biochemical factors such as hypoxia and immune checkpoint pathways. Hypoxia, defined as a state of reduced oxygen availability, is one of a key driver of OSCC progression and therapeutic resistance.2 It promotes malignant phenotypes, induces genetic and epigenetic changes, and impairs chemotherapy efficacy by upregulating drug resistance genes such as MDR1, which encodes P-glycoprotein (P-gp) that facilitates drug efflux. Additionally, hypoxia-induced acidosis and abnormal vasculature hinder the delivery of pH-sensitive chemotherapeutics like doxorubicin and docetaxel. As an alternative, targeted drug delivery systems, particularly ferritin nanocages, offer a promising solution. Ferritin, a natural iron-storage protein, binds transferrin receptor 1 (TfR1), which is highly overexpressed OSCC, enabling receptor-mediated tumor-specific delivery.3 Its pH-responsive assembly allows efficient drug encapsulation and controlled release, while its biocompatibility and modifiable surface enable multifunctional applications. This makes ferritin nanoparticles or nanocages an ideal platform to selectively target hypoxic tumor regions with high TfR1 expression, delivering hypoxia-alleviating or hypoxia-targeted therapies to improve outcomes. Catechins are polyphenolic compounds found abundantly in dietary and medicinal plants, known for their preventive and therapeutic effects against chronic diseases, including cancers such as prostate and breast cancer. Catechins reduce oxidative stress and inflammation under hypoxic conditions by modulating reactive oxygen species (ROS) production, inhibiting NADPH oxidase, and downregulating hypoxia-inducible factor-1 (HIF-1) signaling. Despite their anticancer potential—through apoptosis induction and proliferation inhibition—their clinical application is limited by poor solubility, low bioavailability, instability, rapid degradation, and limited tissue penetration.4 Considering hypoxia’s pivotal role in OSCC progression and chemoresistance, delivery via ferritin nanoparticles represents a promising therapeutic approach to exploit this condition. We hypothesize that catechin-loaded ferritin nanoparticles will preferentially accumulate in hypoxic tumor regions with elevated TfR1 expression, improving intracellular catechin uptake and anticancer efficacy by overcoming hypoxia-induced drug resistance and inhibiting tumor progression in OSCC. This efficacy can further be enhanced by adding a chemotherapeutic prodrug/drug using a combinatorial therapy.

OSCC, tumour microenvironment (TME), Hypoxia, Ferritin nanoparticle, Catechins, transferrin receptor 1 (TfR1)