title: Mustard-inspired delivery shuttle for enhanced blood-brain barrier penetration and effective drug delivery in glioma therapy.
abstract: Effective penetration through the blood-brain barrier (BBB) remains a challenge for the treatment of many brain diseases. In this study, a small molecule, sinapic acid (SA), extracted from mustard, was selected as a novel bioinspired BBB-permeable ligand for efficient drug delivery in glioma treatment. SA was conjugated on the surface of zwitterionic polymer poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC)-encapsulated bovine serum albumin (BSA)-based nanoparticles, yielding nBSA-SA. The PMPC shell serves as a protective layer to prolong the in vivo blood circulation time with a better chance to cross the BBB. Furthermore, temozolomide (TMZ), which can be loaded onto the nanoparticles via electrostatic interactions with acrylic acid (AA) to generate AA-nBSA-SA-TMZ, was applied as an excellent chemotherapeutic drug for glioma therapy. The obtained nanoparticles with a distinct size show great BBB permeability. Through the mechanism study, it was found that the cell internalization of the SA-conjugated nanoparticles is an energy-dependent process with only transient disruption of the BBB. The biological evaluation results unambiguously suggest that drug-loaded nanoparticles can lead to strong apoptosis on the tumor site and increase the median survival time of glioma-bearing mice. Overall, this novel BBB-permeable ligand SA paves the way for the delivery of cargo into the brain and provides a powerful nanoplatform for glioma therapy via intravenous administration.
authors.affiliation: School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China. xyzhu@sjtu.edu.cn jxcindy@sjtu.edu.cn.
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.forename: Pei
authors.initials: P
authors.lastname: Sun
authors.forename: Mingming
authors.initials: M
authors.lastname: Lv
authors.forename: Gangsheng
authors.initials: G
authors.lastname: Tong
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Zhu
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002417:Cattle; D045744:Cell Line, Tumor; D003373:Coumaric Acids / Q000737:chemistry* / Q000378:metabolism; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D009149:Mustard Plant / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D011109:Polymethacrylic Acids / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000378:metabolism; D000077204:Temozolomide; D014018:Tissue Distribution
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003373:Coumaric Acids; D004337:Drug Carriers; D011109:Polymethacrylic Acids; C115766:poly(2-methacryloyloxyethyl-phosphorylcholine); D010767:Phosphorylcholine; D012710:Serum Albumin, Bovine; C073734:sinapinic acid; D003606:Dacarbazine; D000077204:Temozolomide