Breast cancer brain metastases (BCBMs) are advanced breast cancer diseases common in many patients. They are one of the major breast cancer subtypes and their performance status is the major cause of the course of the disease and survival time following a diagnosis of brain metastasis. In the process of managing BCBMs, unique challenges include overcoming the blood-brain barrier (BBB) and cell-specific targets, and resistance to conventional systemic therapies, as BCBMs mainly occur in the pretreated patient population. The development of BBB-crossing and selective targeting nanomedicine for BCBMs has become increasingly important. Here, we have developed cisplatin prodrug-loaded brain-accumulating nanoparticles to deliver the active drug cisplatin to the mitochondria of the cancer cells. Though the brain cell matrix is very complex and heterogeneous, we were able to show the selective targeting ability of these nanoparticles towards the BCBM cells over non-cancerous brain cells after crossing the BBB. These nanoparticles were able to lower nucleotide excision repair and decrease the base excision repair in the mitochondria which leads to the decrease in SIRT3 protein and ATP production levels in the BCBM cells. The BCMB cells xenograft showed the decrease in the tumor size and volume and as well as SIRT3 levels.

Selective targeting of breast cancer brain metastases by Cisplatin prodrug nano-formulation

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.