<p>Preparation and Evaluation of Cabazitaxel-Loaded Bovine Serum Albumin Nanoparticles for Prostate Cancer</p>

Abstract

Purpose Cabazitaxel (CBZ) is a new taxane-based antitumor drug approved by the FDA for the treatment of prostate cancer, especially for patients with advanced prostate cancer for whom docetaxel is ineffective or causes aggravation. However, Tween 80 injection can cause serious allergic reactions, and CBZ itself has strong toxicity, adverse reactions, and poor tumor selectivity, which greatly limits its clinical applications. Therefore, the CBZ-loaded bovine serum albumin nanoparticles (CBZ-BSA-Gd-NPs) were developed to overcome the allergenic response of Tween 80 and realize the integration of diagnosis and treatment. Methods CBZ-BSA-Gd-NPs were prepared by the biomineralization method. The characterization, magnetic resonance imaging (MRI), safety, and antitumor activity of the nanoparticles were evaluated in vitro and in vivo. Results The prepared nanoparticles were uniform in size (166 nm), with good MRI performance and stability over 24 h. Compared with CBZ-Tween 80 injection, CBZ-BSA-Gd-NPs showed much lower hemolysis, similar tumor inhibition, and enhanced cellular uptake in vitro. The pharmacokinetic behavior of CBZ-BSA-Gd-NPs in rats showed that the retention time of the nanoparticles was prolonged, the clearance rate decreased, and the area under the drug-time curve increased. The distribution of CBZ-BSA-Gd-NPs in nude mice was characterized by UPLC-MS/MS and MRI, and the results showed that CBZ-BSA-Gd-NPs could effectively target tumor tissues with reduced distribution in the heart, liver, spleen, lungs, and kidneys compared with CBZ-Tween 80, which indicated that CBZ-BSA-Gd-NPs not only had a passive targeting effect on tumor tissue but also achieved the integration of diagnosis and treatment. In vivo, CBZ-BSA-Gd-NPs showed improved tumor inhibitory effect with a safer profile. Conclusion In summary, CBZ-BSA-Gd-NPs can serve as an effective therapeutic drug carrier to deliver CBZ into prostate cancer, and realize the integration of diagnosis and therapy.

Combination Therapy of Metastatic Castration-Recurrent Prostate Cancer: Hyaluronic Acid Decorated, Cabazitaxel-Prodrug and Orlistat Co-Loaded Nano-System

“…Combination index (CI) analysis was applied using Chou and Talalay method to evaluate the synergistic effects of ORL and HA-CBZ in one LPNs system on LNCaP cells. 41 Combination Index, when 50% growth inhibition was achieved (CI 50 ), values of ORL/HA-CBZ/LPNs were calculated by the equation: 42 …”

Biocompatible Nanomaterials as an Emerging Technology in Reproductive Health; a Focus on the Male

“…The encapsulated SPIONs facilitated increased contrast enhanced MRI capability when compared to the, commercially available, contrast reagent Resovit ( Fang et al, 2020 ). Similarly, the MRI contrast reagent gadolinium along with cabazitaxel were incorporated within bovine serum albumin NPs by Wan et al (2020) for concurrent treatment and imaging of PC. These researchers applied this untargeted nanosystem to PC-3 cells in vitro and then relied on the enhanced permeability and retention effect for preferential uptake by the tumor xenografts in vivo .…”

Cabazitaxel-Loaded Nanoparticles Reduce the Invasiveness in Metastatic Prostate Cancer Cells: Beyond the Classical Taxane Function

“…CBZ also inhibits genes, proteins, and chemokines known to promote metastatic progression [ 14 ]. Unfortunately, the clinical use of CBZ is limited due to high systemic toxicity [ 15 ]. Treatments targeting tumors require doses that cause severe side-effects and, in many cases, death.…”