title: Delivery of bortezomib with nanoparticles for basal-like triple-negative breast cancer therapy.
abstract: Basal-like triple negative breast cancer (TNBC) has received particular clinical interest due to its high frequency, poor baseline prognosis and lack of effective clinical therapy. Bortezomib, which was the first proteasome inhibitor approved for the treatment of multiple myeloma, has been proven to be worth investigating for this subtype of breast cancer. In our study, the amphiphilic copolymer poly(ethylene glycol)-block-poly(d,l-lactide) (PEG-b-PLA) was utilized as an excellent delivery carrier of bortezomib (BTZ) to overcome its clinical limitations including low water solubility and unstable properties. Bortezomib encapsulated nanoparticles (NPBTZ) can efficiently deliver the drug into both CSCs (cancer stem cells) and non-CSCs, resulting in proliferation inhibition and apoptosis induction. Remarkably, NPBTZ can more effectively affect the stemness of CSCs compared with free BTZ. Administration of this drug delivery system can markedly prolong the bortezomib circulation half-life and augment the enrichment of drugs in tumor tissue, then enhance the suppression of tumor growth, suggesting the therapeutic promise of NPBTZ delivery in basal-like TNBC therapy.
authors.affiliation: The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science & Technology of China, Hefei, Anhui 230027, PR China.
authors.forename: Song
authors.initials: S
authors.lastname: Shen
authors.affiliation: The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science & Technology of China, Hefei, Anhui 230027, PR China.
authors.forename: Xiao-Jiao
authors.initials: XJ
authors.lastname: Du
authors.affiliation: The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science & Technology of China, Hefei, Anhui 230027, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, Anhui 230027, PR China.
authors.forename: Rong
authors.initials: R
authors.lastname: Sun
authors.affiliation: The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science & Technology of China, Hefei, Anhui 230027, PR China.
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Zhu
authors.affiliation: The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science & Technology of China, Hefei, Anhui 230027, PR China; Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, Anhui 230027, PR China; High Magnetic Field Laboratory of CAS, University of Science and Technology of China, Hefei, Anhui 230026, PR China. Electronic address: jwang699@ustc.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D000069286:Bortezomib / Q000008:administration & dosage* / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005079:Excipients; D005260:Female; D006207:Half-Life; D006801:Humans; D007773:Lactates / Q000737:chemistry; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D053758:Nanoparticles / Q000737:chemistry*; D014411:Neoplastic Stem Cells / Q000187:drug effects; D011092:Polyethylene Glycols / Q000737:chemistry; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D005079:Excipients; D007773:Lactates; C088513:poly(lactic acid-ethylene glycol); D011092:Polyethylene Glycols; D000069286:Bortezomib; D046988:Proteasome Endopeptidase Complex
keywords: Basal-like triple negative breast cancer; Bortezomib; Cancer stem cells; Nanoparticle; Poly(ethylene glycol)-block-poly(d,l-lactide)