Role of Serum Protein Acidic and Rich in Cysteine and Human Serum Albumin in Cancer Drug Delivery

Abstract

The main challenge in designing drugs for cancer is treating patients without affecting the patient’s quality of life. Our study focuses on how to utilize the external microenvironment surrounding the cancer cells for efficient drug delivery. Cancer cells have more serum protein acidic and rich in cysteine (SPARC) and collagen than normal cells. SPARC protein plays a crucial role in maintaining the integrity of the extracellular matrix (ECM) by modulating the basal lamina and collagen in the ECM. In our present study, an in-depth analysis was performed to determine the subdomains of Human serum albumin (HSA) (IA, IB, IIA, IIB, IIIA, IIIB) that interact with the SPARC and SPARC-collagen. The binding affinity of the 3D structures of the individual subdomains of HSA with SPARC and SPARC-collagen complex were analyzed in ClusPro 2.0 and ZDOCK servers. Molecular dynamics were performed in GROMACS V.2021.2 for a period of 10 ns. The SPARC and SPARC-collagen complex has a high affinity with the sub-domain IB and IIA. Sub-domain IIA consists of the drug binding site I of HSA; because of that, SPARC-Collagen has shown more binding affinity, and fatty acid site II overlaps with drug binding site I. Root mean square deviation plots show that the HSA-SPARC-collagen complex is more stable during the time course than the HSA-SPARC complex. The radius of gyration of the HSA-SPARC-collagen complex has shown the same compactness as that of the HSA-SPARC complex. Cancer cells develop resistance over time to drugs, which makes it challenging to design the drugs and treat patients. Designing drugs to deliver to the cancer cells with the help of HSA and SPARC bypassing the lysosome degradation system will efficiently deliver the drugs to the cancer cells. In case cancer cells develop resistance to this mechanism, the cancer cells may decrease the SPARC and collagen influx into the cells, resulting in decreased cancer cell proliferation and metastasis rate, providing extra time for the health care workers to provide better therapy to the patients.