Research Projects

Platinum-derived drug cisplatin is one of the important clinically prescribed systemic chemotherapeutic agents to treat a variety of cancers, such as cervical, prostate, and oral cancer. This drug functions by cross-linking DNA strands to prevent their uncoiling during replication, which eventually leads to apoptosis-mediated cell death. Although cisplatin is systemically very effective but fails to control the resurgence due to the limited diffusion (noneffective concentration) at the external surface of squamosal cell carcinoma of the cervix. These cervical cancer cells are currently treated by radiotherapy. The non-effective concentration of systemic cisplatin beyond the basal lamina is the major cause of the resurgence of squamosal cell carcinoma. Thus, to control the resurgence, there will be a need to develop a targeted and sustained external delivery system with mucosa-adhesive properties to treat cervical cancer cells beyond the reach of a systemic supply. Considering this in mind, we have developed an in vitro assembled nano-scaffold of HPV L1 capsid protein virions to encapsulate cisplatin. The building block of the nano-scaffold was recombinantly generated and self-assembled to encapsulate cisplatin in the core of virions. The virions of HPV were reported to internalize in the basal epithelium of the cervix completely. We expect that this chimeric nano-scaffold system will show mucosa adhesive (for prolonged transvaginal external supply) and targeted delivery only to cancer cells for increased cytotoxicity (compared to free cisplatin) to degrade the remaining active squamosal carcinoma cells (the primary reason for resurgence) along with systemic treatment. The selective and complete internalization potential of this system in cervical cancer cells leads to the development of an externally targeted nano-scaffold system for the delivery of encapsulated cisplatin without any dose-dependent side effects. This system may fulfill the aim of developing a programmable nano-scaffold-based platform for cisplatin delivery through vaginal route. The elucidation of molecular mechanisms may provide new knowledge to improve the therapeutic potential of this system. The 3D tomography by FIB-SEM (large volume imaging), together with cryo-electron tomography (lamella) of different cell organelles of in vitro and ex vivo cervicectomy samples treated with this system, will provide a fundamental understanding of the broad-spectrum functionality at the sub-molecular resolution, not yet reported even with the free cisplatin. These studies enlighten new knowledge about the mechanism of cellular internalization, targeting, and trafficking of these vehicles, which will be helpful for the development of these delivery vehicles further for in vivo and clinical trials. The proposed work will lead to the development of a nano-scaffold delivery system for cisplatin to control cervical cancer resurgence through the external vaginal route.