title: Preclinical evaluation of injectable sirolimus formulated with polymeric nanoparticle for cancer therapy.
abstract: Nanoparticles are useful delivery vehicles for promising drug candidates that face obstacles for clinical applicability. Sirolimus, an inhibitor of mammalian target of rapamycin has gained attention for targeted anticancer therapy, but its clinical application has been limited by its poor solubility. This study was designed to enhance the feasibility of sirolimus for human cancer treatment. Polymeric nanoparticle (PNP)-sirolimus was developed as an injectable formulation and has been characterized by transmission electron microscopy and dynamic light scattering. Pharmacokinetic analysis revealed that PNP-sirolimus has prolonged circulation in the blood. In addition, PNP-sirolimus preserved the in vitro killing effect of free sirolimus against cancer cells, and intravenous administration displayed its potent in vivo anticancer efficacy in xenograft tumor mice. In addition, PNP-sirolimus enhanced the radiotherapeutic efficacy of sirolimus both in vitro and in vivo. Clinical application of PNP-sirolimus is a promising strategy for human cancer treatment.
authors.affiliation: Institute for Innovative Cancer Research, Asan Medical Center, Seoul, Korea.
authors.forename: Ha Na
authors.initials: HN
authors.lastname: Woo
authors.forename: Hye Kyung
authors.initials: HK
authors.lastname: Chung
authors.forename: Eun Jin
authors.initials: EJ
authors.lastname: Ju
authors.forename: Joohee
authors.initials: J
authors.lastname: Jung
authors.forename: Hye-Won
authors.initials: HW
authors.lastname: Kang
authors.forename: Sa-Won
authors.initials: SW
authors.lastname: Lee
authors.forename: Min-Hyo
authors.initials: MH
authors.lastname: Seo
authors.forename: Jin Seong
authors.initials: JS
authors.lastname: Lee
authors.forename: Jung Shin
authors.initials: JS
authors.lastname: Lee
authors.forename: Heon Joo
authors.initials: HJ
authors.lastname: Park
authors.forename: Si Yeol
authors.initials: SY
authors.lastname: Song
authors.forename: Seong-Yun
authors.initials: SY
authors.lastname: Jeong
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Choi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007267:Injections; D008297:Male; D051379:Mice; D046529:Microscopy, Electron, Transmission; D050997:Nanomedicine; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D020123:Sirolimus / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D011091:Polyesters; D011108:Polymers; D011838:Radiation-Sensitizing Agents; C492425:methoxy poly(ethylene glycol)-poly(lactide); D011092:Polyethylene Glycols; D020123:Sirolimus