title: HSA coated iron oxide nanoparticles as drug delivery vehicles for cancer therapy.
abstract: An ongoing effort in the field of nanomedicine is to develop nanoplatforms with both imaging and therapeutic functions, the "nanotheranostics". We have previously developed a human serum albumin (HSA) coated iron oxide nanoparticle (HINP) formula and used multiple imaging modalities to validate its tumor targeting attributes. In the current study, we sought to impart doxorubicin (Dox) onto the HINPs and to assess the potential of the conjugates as theranostic agents. In a typical preparation, we found that about 0.5 mg of Dox and 1 mg of iron oxide nanoparticles (IONPs, Fe content) could be loaded into 10 mg of HSA matrices. The resulting D-HINPs (Dox loaded HINPs) have a hydrodynamic size of 50 nm and are able to release Dox in a sustained fashion. More impressively, the HINPs can assist the translocation of Dox across the cell membrane and even its accumulation in the nucleus. In vivo, D-HINPs retained a tumor targeting capability of HINPs, as manifested by both in vivo MRI and ex vivo immunostaining results. In a follow-up therapeutic study on a 4T1 murine breast cancer xenograft model, D-HINPs showed a striking tumor suppression effect that was comparable to that of Doxil and greatly outperformed free Dox. Such a strategy can be readily extended to load other types of small molecules, making HINP a promising theranostic nanoplatform.
authors.affiliation: Department of Radiology, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai 200080, China.
authors.forename: Qimeng
authors.initials: Q
authors.lastname: Quan
authors.forename: Jin
authors.initials: J
authors.lastname: Xie
authors.forename: Haokao
authors.initials: H
authors.lastname: Gao
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Xin
authors.initials: X
authors.lastname: Lin
authors.forename: Andrew
authors.initials: A
authors.lastname: Wang
authors.forename: Henry S
authors.initials: HS
authors.lastname: Eden
authors.forename: Seulki
authors.initials: S
authors.lastname: Lee
authors.forename: Guixiang
authors.initials: G
authors.lastname: Zhang
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use; D001692:Biological Transport; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena; D003692:Delayed-Action Preparations; D004317:Doxorubicin / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005260:Female; D005290:Ferric Compounds / Q000737:chemistry*; D006207:Half-Life; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D008819:Mice, Nude; D012709:Serum Albumin / Q000737:chemistry*; D000075462:Serum Albumin, Human; D013499:Surface Properties; D014018:Tissue Distribution; D047368:Tumor Burden / Q000187:drug effects
chemical_list: C422455:ALB protein, human; D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D005290:Ferric Compounds; D012709:Serum Albumin; C000499:ferric oxide; D004317:Doxorubicin; D000075462:Serum Albumin, Human