title: Cationic Polymethacrylate-Modified Liposomes Significantly Enhanced Doxorubicin Delivery and Antitumor Activity.
abstract: Liposome (LP) encapsulation of doxorubicin (DOX) is a clinically validated method for cancer drug delivery, but its cellular uptake is actually lower than the free DOX. Therefore, we modified DOX-LP with a cationic polymer (Eudragit RL100; ER) to improve its cellular uptake and antitumor activity. The resulting DOX-ERLP was a 190 nm nanoparticle that was absorbed efficiently and caused cancer cell death in 5 hrs. Growth as measured by the MTT assay or microscopic imaging demonstrated that DOX-ERLP has at least a two-fold greater potency than the free DOX in inhibiting the growth of a DOX resistant (MCF7/adr) cell and an aggressive liver cancer H22 cell. Further, its in vivo efficacy was tested in H22-bearing mice, where four injections of DOX-ERLP reduced the tumor growth by more than 60% and caused an average of 60% tumor necrosis, which was significantly better than the DOX and DOX-LP treated groups. Our work represents the first use of polymethacrylate derivatives for DOX liposomal delivery, demonstrating the great potential of cationic polymethacrylate modified liposomes for improving cancer drug delivery.
authors.affiliation: College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China.
authors.forename: Wenxi
authors.initials: W
authors.lastname: Wang
authors.affiliation: College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China.
authors.forename: Anna
authors.initials: A
authors.lastname: Shao
authors.affiliation: College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China.
authors.forename: Jinzhang
authors.initials: J
authors.lastname: Fang
authors.affiliation: College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China.
authors.forename: Jennifer Jin
authors.initials: JJ
authors.lastname: Ruan
authors.affiliation: College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China.
authors.forename: Benfang Helen
authors.initials: BH
authors.lastname: Ruan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D002412:Cations / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D065546:Drug Liberation; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D008813:Mice, Inbred ICR; D053758:Nanoparticles / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D010316:Particle Size; D011109:Polymethacrylic Acids / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D002412:Cations; D008081:Liposomes; D011109:Polymethacrylic Acids; C030613:polymethacrylic acid; D004317:Doxorubicin