title: Comparison of active and passive targeting of doxorubicin for somatostatin receptor 2 positive tumor models by octreotide-modified HPMA copolymer-doxorubicin conjugates.
abstract: Somatostatin receptor 2 (SSTR2), specifically over-expressed on many tumor cells, is a potential receipt for active targeting in cancer therapy. In the present study, octreotide (Oct), which had high affinity to SSTR2, was attached to N-(2-hydroxypropyl) methacrylamide (HPMA) polymeric system to enhance the antitumor efficiency of the anticancer drug doxorubicin (DOX). Two kinds of cell lines (HepG2 and A549), which overexpress SSTR2, were chosen as cell models. Compared with non-modified conjugates, Oct-modified conjugates exhibited superior cytotoxicity and intracellular uptake on both HepG2 and A549 cell lines. This might be due to the mechanism of receptor-mediated endocytosis. Subsequently, the in vivo biodistribution and antitumor activity evaluations showed that Oct modification significantly improved the tumor accumulation and antitumor efficacy of HPMA copolymer conjugates in SSTR2 over-expressed Kunming mice bearing H22 tumor xenografts. In summary, Oct-modified HPMA polymer-DOX conjugates might be a promising system for the treatment of SSTR2 over-expressed cancers.
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy , Sichuan University , Chengdu , P.R. China.
authors.forename: Shuang
authors.initials: S
authors.lastname: He
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy , Sichuan University , Chengdu , P.R. China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy , Sichuan University , Chengdu , P.R. China.
authors.forename: Lian
authors.initials: L
authors.lastname: Li
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy , Sichuan University , Chengdu , P.R. China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Yang
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy , Sichuan University , Chengdu , P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy , Sichuan University , Chengdu , P.R. China.
authors.forename: Shan
authors.initials: S
authors.lastname: Guan
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy , Sichuan University , Chengdu , P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy , Sichuan University , Chengdu , P.R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhu
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy , Sichuan University , Chengdu , P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Jin
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy , Sichuan University , Chengdu , P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000178:Acrylamides / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology*; D016503:Drug Delivery Systems; D006801:Humans; D008297:Male; D008689:Methacrylates / Q000737:chemistry* / Q000493:pharmacokinetics; D051379:Mice; D015282:Octreotide / Q000737:chemistry* / Q000493:pharmacokinetics; D017481:Receptors, Somatostatin / Q000187:drug effects* / Q000378:metabolism; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000178:Acrylamides; D000903:Antibiotics, Antineoplastic; D008689:Methacrylates; D017481:Receptors, Somatostatin; C574734:SSTR2 protein, human; C482378:N-(2-hydroxypropyl)methacrylamide co-polymer-doxorubicin conjugate; D004317:Doxorubicin; D015282:Octreotide; C032802:hydroxypropyl methacrylate
keywords: Doxorubicin; octreotide; octreotide-modified HPMA copolymer-doxorubicin conjugates; somatostatin receptor 2; tumor targeting