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

MULLAPUDI SNEHA SREE

Publication

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

MULLAPUDI SNEHA SREE

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.