Abstract Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related mortality in the US (2023) with the 5-year survival rate standing only at less than 9%. Three major issues in pancreatic tumor treatment are; poor availability of anticancer molecules due to limited blood supply to pancreas, development of resistance to first line agents e.g. gemcitabine and extensive fibrosis in tumor stroma. There is an urgent need for a novel and effective therapeutic strategy for PDAC via simultaneously targeting tumor and its microenvironment. Given the central role of Myc as a mediator of multiple cell proliferation and survival pathways, it is very essential to target the proto-oncogenic expression of Myc and controlling K-Ras mediated drug resistance in pancreatic cancer. BRD4 Proteolysis Targeting Chimera (PROTAC) is an effective way to silence BRD4 and Myc. On another side, collagen type I dense extracellular matrix of solid tumor severely restricts the uptake of drug, monoclonal antibodies and nanotherapeutics within pancreatic tumor. Overexpressed focal adhesion kinase (FAK) in pancreatic cancer plays role in angiogenesis, fibrosis and metastasis. Secreted protein acidic and rich in cysteine (SPARC) and KRAS mutation collectively facilitate the uptake of albumin into stroma and PDAC cell, respectively. Based on our promising preliminary results, the parent NIH R16 award was proposed to explore the albuminosomes for pancreatic tumor specific delivery of BRD4 PROTAC with simultaneous compromising the fibrotic stoma using FAK inhibitor-PND 1186. The requested grant supplemental equipment – ECHO Revolution hybrid fluorescence microscope will be of great help in investigating the cellular uptake mechanism of albuminosomes in 2D and 3D cell culture of pancreatic cells. The uptake of nanoparticles in tumor stroma and cancer cells is essential for enhancing its anticancer efficacy. High resolution microscope with automated scanning capability will be useful in (a) identifying and locating the nanoparticles within PDAC stroma and KRAS mutant PDAC cancer cells (b) Penetration and anticancer efficacy evaluation using multicellular 3D spheroids of PDAC cell and cancer associate fibroblasts. The microscope will be housed in the PI’s laboratory. Undergraduate and graduate students including URM students will use it routinely.