NANO-PARTICULATE DRUG CARRIERS FOR EFFECTIVE TARGETING AND DRUG DELIVERY TO BLADDER TUMORS

Abstract

Current intravesical chemotherapy for bladder cancer (BC) has limited efficacy due to lack of specificity of drugs/drug carriers for the tumors and the short residence time of the instilled agent in the bladder due to urine voiding. To address these challenges, albumin-based carriers in two forms i.e., native albumin chains (~16nm) and albumin nanoparticles (HNP ~100nm), both conjugated with a peptide (txCD47) that can specifically target the cluster of differentiation 47 surface receptor overexpressed on BC cells were developed. txCD47-functionalized albumin carrier reduced the IC50 of the loaded drug in the carriers by a factor of 5-10 compared to that of the free drug. The preferential targeting of bladder tumor tissue by txCD47-HNP was confirmed in a mouse orthotopic BC model. Treatment of urine samples from four patients with fluorescence-labeled txCD47-HNP resulted in 83-97% fluorescence-positive cells. Finally, glucose-conjugated albumin in presence of hyperthermia enhanced the cytotoxicity of the loaded drug.