Research Projects

The proposed research is fundamentally motivated by the urgent need for superior imaging and treatment for breast cancer (BC) patients with diabetes mellitus comorbidity often represented with altered tumor microenvironment, compromised immune functions and decreased responsiveness to conventional treatments, leading to worse outcomes and increased mortality as compared to patients suffering from BC only. It has also been reported that age-standardized cancer incidences were projected to increase 2.4 times faster with people with diabetes. NIR-II (1000-1700nm) fluorescence imaging is a non-radiative visualization technique with high tissue penetration and prominent signal-to-noise ratio for the superior optical detection of tumors and subsequent surgical navigations. This approach has not been currently explored in India and thus highly warranted for indigenous product development. The NIR-II window also allows localized adjuvant photothermal & photodynamic therapies (PT/PD-T) of deep-seated solid tumors. Plant-derived extracellular vesicles (P-EVs) are biocompatible nanocarriers in which their lipid bilayer membrane protects the encapsulated cargo from degradation and non-specific release. These P-EVs can be hybridized with NIR-II dye loaded liposomes using polyethylene glycol (PEG)-mediated membrane fusion, generating hybrid vesicles (HVs). These HVs will inherit properties of both nanosystems, such as increased payload capacity for NIR-II dye, surface modification for enhanced targeting as well as inherent therapeutic properties of P-EVs. On reaching the tumor microenvironment, these HVs can release their encapsulated NIR-II dye which enables deeper tissue imaging with minimal background noise and high-contrast visualization of tumor margins. Furthermore, upon NIR-II laser irradiation, these dyes can generate localized hyperthermia and reactive oxygen species, facilitating PTT & PDT for tumor ablation. Simultaneously, on reaching liver tissue because of the reticuloendothelial system (RES) capture, the inherent molecules present in the P-EVs might help in controlling the complications of T2DM. Overall, the proposed research aims to synthesize a novel breast tumor targeted, hybrid vesicles encapsulating NIR-II fluorescence dye and surface modified with galectin-3 targeting ligand (G3-C12 peptide) that will allow for accurate imaging and efficient ablation of tumor. In addition, G3-C12 peptide would also help neutralizing circulating galectin-3 that reduce glucose uptake in skeletal and adipose tissue and enhance glucose production by liver, a typical complication associated with T2DM. Thus, modulating metabolic pathways and enabling superior imaging and tumor ablation in breast cancer and diabetes mellitus comorbid animal models.