Tumor-targeting albumin nanoparticles as an efficacious drug delivery system and potential diagnostic tool in non-muscle-invasive bladder cancer therapy.

Current intravesical chemotherapy for non-muscle invasive bladder cancer (NMIBC) has limited efficacy due to loss of the instilled agent from urine voiding and the agent's lack of specificity for the tumors. We developed a nanocarrier (txCD47-HNP, ∼100 nm) based on human serum albumin conjugated with a peptide that targets the cluster of differentiation 47 receptor overexpressed on bladder cancer (BC) cells. The IC50 of gemcitabine elaidate (GEM) loaded in the txCD47-HNP was almost an order of magnitude lower than that of free GEM. In a mouse orthotopic BC model, GEM loaded in txCD47-HNP effectively reduced the tumor burden. Tumor cells in BC patients' urine can also be targeted by fluorescence-labeled txCD47-HNP resulting in >83 % of the cells exhibiting fluorescence. Thus, txCD47-HNP can potentially be a theranostic agent in NMIBC management by serving as a targeted drug delivery vehicle as well as an alternative to urine cytology.

Glycosylated phospholipid-coated upconversion nanoparticles for bioimaging of non-muscle invasive bladder cancers.

Detection of non-muscle invasive bladder cancer (NMIBC) is crucial to facilitate complete tumor resection, thus improving the survival rate as well as reducing the recurrence frequency and treatment expense. Fluorescence imaging cystoscopy is an effective method for the detection of NMIBC. However, its application is limited as the commonly applied fluorescent agents such as dyes and photosensitizers usually lack specific tumor accumulation and are vulnerable to photobleaching. Furthermore, the broad emission band of conventional fluorescent agents limits their imaging and detection efficacy. To overcome these limitations, upconversion nanoparticles (UCNPs) have been selected as the fluorescent agent, due to their resistance to photobleaching, less background auto-fluorescence, and narrow emission bands. In order to achieve active tumor targeting, the UCNPs are coated with a glycosylated phospholipid layer. The glycosylated phospholipid-coated UCNPs exhibited high selective accumulation in cancer cells over normal cells and enhanced the upconversion luminescence (UCL) (at 540 nm and 660 nm) from bladder cancer cells under 980 nm laser irradiation. Glycosylated phospholipid coating that promotes uptake of UCNPs by cancer cells, and UCL emitted from UCNPs under NIR (980 nm) laser irradiation for cancer cell imaging.

Receptor-Targeting Drug and Drug Carrier for Enhanced Killing Efficacy against Non-Muscle-Invasive Bladder Cancer.

Intravesical chemotherapy for bladder cancer has limited efficacy due to the lack of specificity of drugs/drug carriers toward the cancer cells as well as inadequate drug residence time in the bladder due to urine voiding. From analyses of surface receptor expression of UMUC3 bladder cancer cells and the targeting efficacy of different peptides, we selected a peptide (txCD47) that targets the cluster of differentiation 47 (CD47) surface protein overexpressed on these cells as a targeting ligand for docetaxel (DTX) and an albumin nanocarrier of DTX. The IC50 of DTX conjugated to txCD47 (txCD47-DTX) in a 1:1 molar ratio was lowered by a factor of 3 from that of free DTX. By using the albumin molecule (txCD47-BSA) as a delivery vehicle, different amounts of txCD47 can be conjugated to investigate the effects of peptide concentration on targeting efficacy. The IC50 of DTX loaded in txCD47-BSA with 14 txCD47 per albumin molecule was 1 order of magnitude lower than that of free DTX, and a factor of 4 lower than that of txCD47-BSA with 8 txCD47 per albumin molecule. DTX was released from the albumin nanocarrier at a controlled rate, and the endocytosed carrier will release most of its payload inside the cells within 72 h. Thus, txCD47 promotes delivery of the drug/drug carrier, and the resultant enhanced killing efficacy of the drug can potentially alleviate some of the limitations of intravesical chemotherapy against bladder cancer.