title: Hydrophobic Cysteine Poly(disulfide)-based Redox-Hypersensitive Nanoparticle Platform for Cancer Theranostics.
abstract: Selective tumor targeting and drug delivery are critical for cancer treatment. Stimulus-sensitive nanoparticle (NP) systems have been designed to specifically respond to significant abnormalities in the tumor microenvironment, which could dramatically improve therapeutic performance in terms of enhanced efficiency, targetability, and reduced side-effects. We report the development of a novel L-cysteine-based poly (disulfide amide) (Cys-PDSA) family for fabricating redox-triggered NPs, with high hydrophobic drug loading capacity (up to 25 wt% docetaxel) and tunable properties. The polymers are synthesized through one-step rapid polycondensation of two nontoxic building blocks: L-cystine ester and versatile fatty diacids, which make the polymer redox responsive and give it a tunable polymer structure, respectively. Alterations to the diacid structure could rationally tune the physicochemical properties of the polymers and the corresponding NPs, leading to the control of NP size, hydrophobicity, degradation rate, redox response, and secondary self-assembly after NP reductive dissociation. In vitro and in vivo results demonstrate these NPs' excellent biocompatibility, high selectivity of redox-triggered drug release, and significant anticancer performance. This system provides a promising strategy for advanced anticancer theranostic applications.
authors.affiliation: Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 (USA).
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 (USA).|Department of Endoscopy, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, Jiangsu, 210029 (P.R. China).
authors.forename: Lili
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 (USA).
authors.forename: Xiaoding
authors.initials: X
authors.lastname: Xu
authors.affiliation: David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139 (USA).
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bertrand
authors.affiliation: Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 (USA).
authors.forename: Won Ii
authors.initials: WI
authors.lastname: Choi
authors.affiliation: Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 (USA).
authors.forename: Basit
authors.initials: B
authors.lastname: Yameen
authors.affiliation: Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 (USA).
authors.forename: Jinjun
authors.initials: J
authors.lastname: Shi
authors.affiliation: Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 (USA).
authors.forename: Vishva
authors.initials: V
authors.lastname: Shah
authors.affiliation: Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 (USA).
authors.forename: Matthew
authors.initials: M
authors.lastname: Mulvale
authors.affiliation: Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 (USA).
authors.forename: James L
authors.initials: JL
authors.lastname: MacLean
authors.affiliation: Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 (USA). ofarokhzad@zeus.bwh.harvard.edu.|King Abdulaziz University, Jeddah (Saudi Arabia). ofarokhzad@zeus.bwh.harvard.edu.
authors.forename: Omid C
authors.initials: OC
authors.lastname: Farokhzad
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003545:Cysteine / Q000737:chemistry*; D004220:Disulfides / Q000737:chemistry; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry; D031541:Fluorescence Resonance Energy Transfer; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy; D010084:Oxidation-Reduction; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D043823:Taxoids / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D000068936:Theranostic Nanomedicine
chemical_list: D000970:Antineoplastic Agents; D004220:Disulfides; D004337:Drug Carriers; D011108:Polymers; D043823:Taxoids; D000077143:Docetaxel; D011092:Polyethylene Glycols; D003545:Cysteine
keywords: cysteine; disulfide; hydrophobic; polymeric nanoparticle; redox response