title: Improvement of anti-tumor abilities on human non-small cell lung carcinoma by micellization and cross-linking of N-(2-hydroxypropyl) methacrylamide copolymers.
abstract: Non-small cell lung carcinoma is one of the most frequently occurred cancers with a very high rate of recurrence. Self-assembly N-(2-hydroxypropyl) methacrylamide (HPMA) micelles and cross-linked micelles were developed to improve antitumor ability of linear HPMA copolymer. The characters of HPMA micelles were investigated and compared using human non-small cell lung carcinoma 3-D culture model and nude mice xenograft model. Cross-linked micelles showed highest cytotoxicity on A549 cell monolayers after a short time treatment in vitro. Moreover, both of the two micelles exhibited better in vitro anti-tumor activity on A549 tumor spheroids than linear HPMA conjugates especially the cross-linked micelles. On BALB/c nude mice bearing A549 xenograft tumors, the cross-linked micelles exhibited the greatest tumor accumulation and the best anti-tumor activity due to the highly improved stabilities and the more pronounced enhanced permeability and retention (EPR) effect, which were followed by the non-cross-linked micelles. Meanwhile, neither the two micelles nor the linear HPMA copolymers showed significant toxicity on the main organs of mice while free doxorubicin (DOX) showed obvious cardiac toxicity. All the results suggested that micellization improved the anti-tumor activity of HPMA copolymers on A549 human non-small cell lung carcinoma, furthermore, cross-linked HPMA copolymer micelles with pH-sensitivity and biodegradability showed more excellent anti-tumor activity.
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu , PR 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 , PR China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Xu
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu , PR 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 , PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000178:Acrylamides / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry*; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D045744:Cell Line, Tumor; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D004355:Drug Stability; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008823:Micelles; D011108:Polymers / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: D000178:Acrylamides; D003432:Cross-Linking Reagents; D008823:Micelles; D011108:Polymers; D004317:Doxorubicin; C032976:N-(2-hydroxypropyl)methacrylamide
keywords: Cross-link; micelles; non-small cell lung cancer; pH-responsive