title: Targeted nanoparticles encapsulating (-)-epigallocatechin-3-gallate for prostate cancer prevention and therapy.
abstract: Earlier we introduced the concept of 'nanochemoprevention' i.e. the use of nanotechnology to improve the outcome of cancer chemoprevention. Here, we extended our work and developed polymeric EGCG-encapsulated nanoparticles (NPs) targeted with small molecular entities, able to bind to prostate specific membrane antigen (PSMA), a transmembrane protein that is overexpressed in prostate cancer (PCa), and evaluated their efficacy in preclinical studies. First, we performed a molecular recognition of DCL- and AG-PEGylation on ligand binding on PSMA active site. Next, the biocompatible polymers PLGA-PEG-A were synthesized and used as base to conjugate DCL or AG to obtain the respective copolymers, needed for the preparation of targeted NPs. The resulting EGCG encapsulating NPs led to an enhanced anti-proliferative activity in PCa cell lines compared to the free EGCG. The behavior of EGCG encapsulated in NPs in modulating apoptosis and cell-cycle, was also determined. Then, in vivo experiments, in mouse xenograft model of prostatic tumor, using EGCG-loaded NPs, with a model of targeted nanosystems, were conducted. The obtained data supported our hypothesis of target-specific enhanced bioavailability and limited unwanted toxicity, thus leading to a significant potential for probable clinical outcome.
authors.affiliation: Department of Chemistry and Pharmacy, Laboratory of Nanomedicine, University of Sassari, 07100 Sassari, Italy.
authors.forename: Vanna
authors.initials: V
authors.lastname: Sanna
authors.affiliation: School of Medicine and Public Health, Department of Dermatology, University of Wisconsin-Madison, Madison WI 53706, USA.
authors.forename: Chandra K
authors.initials: CK
authors.lastname: Singh
authors.affiliation: School of Medicine and Public Health, Department of Dermatology, University of Wisconsin-Madison, Madison WI 53706, USA.
authors.forename: Rahime
authors.initials: R
authors.lastname: Jashari
authors.affiliation: School of Medicine and Public Health, Department of Dermatology, University of Wisconsin-Madison, Madison WI 53706, USA.
authors.forename: Vaqar M
authors.initials: VM
authors.lastname: Adhami
authors.affiliation: School of Medicine and Public Health, Department of Dermatology, University of Wisconsin-Madison, Madison WI 53706, USA.
authors.forename: Jean Christopher
authors.initials: JC
authors.lastname: Chamcheu
authors.affiliation: School of Medicine and Public Health, Department of Dermatology, University of Wisconsin-Madison, Madison WI 53706, USA.|Department of Zoology, University of AL-Azhar, Cairo, Egypt.
authors.forename: Islam
authors.initials: I
authors.lastname: Rady
authors.affiliation: Department of Chemistry and Pharmacy, Laboratory of Nanomedicine, University of Sassari, 07100 Sassari, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Sechi
authors.affiliation: School of Medicine and Public Health, Department of Dermatology, University of Wisconsin-Madison, Madison WI 53706, USA.
authors.forename: Hasan
authors.initials: H
authors.lastname: Mukhtar
authors.affiliation: School of Medicine and Public Health, Department of Dermatology, University of Wisconsin-Madison, Madison WI 53706, USA.
authors.forename: Imtiaz A
authors.initials: IA
authors.lastname: Siddiqui
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage* / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding; D065546:Drug Liberation; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008297:Male; D051379:Mice; D008968:Molecular Conformation; D058990:Molecular Targeted Therapy; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D016588:Anticarcinogenic Agents; D004337:Drug Carriers; D008024:Ligands; D011091:Polyesters; C000589473:polyethylene glycol-poly(lactide-co-glycolide); D011092:Polyethylene Glycols; D002392:Catechin; C045651:epigallocatechin gallate