Prostate-specific membrane antigen targeted, glutathione-sensitive nanoparticles loaded with docetaxel and enzalutamide for the delivery to prostate cancer

Abstract

Prostate cancer (PCa) is the most common malignant tumor in men. Chemotherapy with docetaxel (DTX) and novel hormonal agents such as enzalutamide (EZL) and abiraterone are the preferred first-line therapeutic regimens. Prostate-specific membrane antigen (PSMA) is overexpressed on the surface of PCa cells. This study aimed to prepare a PSMA targeted (Glutamate-Urea-Lysine, GUL ligand modified), glutathione (GSH)-sensitive (Cystamine, SS), DTX and EZL co-loaded nanoparticles (GUL-SS DTX/EZL-NPs) to treat PCa. Polyethylene glycol (PEG) was conjugated with oleic acid (OA) using a GSH-sensitive ligand: cystamine (PEG-SS-OA). GUL was covalently coupled to PEG-SS-OA to achieve GUL-PEG-SS-OA. GUL-PEG-SS-OA was used to prepare GUL-SS DTX/EZL-NPs. To evaluate the in vitro and in vivo efficiency of the system, human prostate cancer cell lines and PCa cells bearing mice were applied. Single drug-loaded nanoparticle and free drugs systems were utilized for the comparison of the anticancer ability. GUL-SS DTX/EZL-NPs showed a size of 143.7 ± 4.1 nm, with a PDI of 0.162 ± 0.037 and a zeta potential of +29.1 ± 2.4 mV. GUL-SS DTX/EZL-NPs showed high cancer cell uptake of about 70%, as well as higher cell growth inhibition efficiency (a maximum 79% of cells were inhibited after treatment) than single drug-loaded NPs and free drugs. GUL-SS DTX/EZL-NPs showed the most prominent tumor inhibition ability and less systemic toxicity. The novel GUL-SS DTX/EZL-NPs could be used as a promising system for PCa therapy.

Binary Nanodrug-Delivery System Designed for Leukemia Therapy: Aptamer- and Transferrin-Codecorated Daunorubicin- and Luteolin-Coloaded Nanoparticles

“…The EE of AP/Tf-Drn/Lut NPs and other samples was >85%. The size and EE of AP/Tf-Drn/Lut NPs, AP-Drn NPs, and Tf-Lut NPs showed no obvious change during the 4 days of the study ( Figure 2A and B ), which is similar to the finding of Chen et al, 35 proving the stability of these systems.…”

Laser-activated nanoparticles for ultrasound/photoacoustic imaging-guided prostate cancer treatment

“…PSMA is the most attractive of prostate antigen, which is highly expressed in prostate epithelial cells ( Ceci et al, 2017 ). Thus, PSMA has been considered as a potential target for PCa targeted diagnosis and therapy ( Sun et al, 2021 ; Chen et al, 2022 ; Guo et al, 2022 ).…”

“…The most attractive of the prostate antigens is prostate-specific membrane antigen (PSMA), which is a membrane-bound zinc metalloproteinase mainly expressed by prostate epithelial cells ( Ceci et al, 2017 ). PSMA has been used as a target for targeted therapy or targeted delivery of nanocarriers ( Sun et al, 2021 ; Chen et al, 2022 ; Guo et al, 2022 ). Recently, triggerable drug-loaded nanocarriers have been combined with various internal or external stimuli to reduce systemic toxicity ( Wang et al, 2018 ).…”

Analysis of prostate cancer using serum surface-enhanced Raman spectroscopy and multivariate statistical algorithm

“…Although serum PSA detection is a common method for the diagnosis of prostate cancer, the detection results are not stable, and there are often false positive or false negative errors. And MRI [4] is the first noninvasive method for the diagnosis of prostate cancer, however, the sensitivity and specificity of MRI in the diagnosis of prostate cancer vary greatly in different studies. Therefore, it is very important to explore a screening method with high sensitivity, specificity, rapidity and convenience.…”