title: Nanoencapsulation of natural triterpenoid celastrol for prostate cancer treatment.
abstract: Celastrol (CL), a triterpenoid extracted from the Chinese herb Tripterygium wilfordii, has recently attracted interest for its potential antitumor effects. However, unfavorable physicochemical and pharmacokinetics properties such as low solubility, poor bioavailability, and systemic toxicity, are limiting its therapeutic application. In this context, the development of innovative nanocarriers can be useful to overcome these issues, and nanoencapsulation would represent a powerful strategy. In this study, we developed novel CL-loaded poly(ε-caprolactone) nanoparticles (NPs), and investigated their antiproliferative efficacy on prostate cancer cells. CL-NPs were prepared using a nanoprecipitation method and fully characterized by physicochemical techniques. The antiproliferative effects on LNCaP, DU-145, and PC3 cell lines of CL-NPs, compared to those of free CL at different concentrations (0.5, 1.0, and 2.0 µM), were investigated. Moreover, fluorescence microscopy was utilized to examine the cellular uptake of the nanosystems. Furthermore, to elucidate impact of nanoencapsulation on the mechanism of action, Western analyses were conducted to explore apoptosis, migration, proliferation, and angiogenesis alteration of prostate cancer cells. The results confirmed that CL-NPs inhibit proliferation dose dependently in all prostate cancer cells, with inhibitory concentration₅₀ less than 2 µM. In particular, the NPs significantly increased cytotoxicity at lower/medium dose (0.5 and 1.0 µM) on DU145 and PC3 cell lines with respect to free CL, with modulation of apoptotic and cell cycle machinery proteins. To date, this represents the first report on the development of biocompatible polymeric NPs encapsulating CL. Our findings offer new perspectives for the exploitation of developed CL-NPs as suitable prototypes for prostate cancer treatment.
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari, Sassari, Italy ; Laboratory of Nanomedicine, University of Sassari, Sassari, Italy.
authors.forename: Vanna
authors.initials: V
authors.lastname: Sanna
authors.affiliation: Department of Dermatology, University of Wisconsin, Madison, WI, USA.
authors.forename: Jean Christopher
authors.initials: JC
authors.lastname: Chamcheu
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari, Sassari, Italy.
authors.forename: Nicolino
authors.initials: N
authors.lastname: Pala
authors.affiliation: Department of Dermatology, University of Wisconsin, Madison, WI, USA.
authors.forename: Hasan
authors.initials: H
authors.lastname: Mukhtar
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari, Sassari, Italy ; Laboratory of Nanomedicine, University of Sassari, Sassari, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Sechi
authors.affiliation: Department of Dermatology, University of Wisconsin, Madison, WI, USA.
authors.forename: Imtiaz Ahmad
authors.initials: IA
authors.lastname: Siddiqui
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002152:Calorimetry, Differential Scanning; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004705:Endocytosis / Q000187:drug effects; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D010316:Particle Size; D053978:Pentacyclic Triterpenes; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D017550:Spectroscopy, Fourier Transform Infrared; D013059:Spectrum Analysis, Raman; D055672:Static Electricity; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D053978:Pentacyclic Triterpenes; D014315:Triterpenes; C050414:celastrol
keywords: celastrol; nanoparticles; poly(ε-caprolactone); prostate cancer; tripterine