학술논문

Structure-to-Efficacy Relationship of HPMA-Based Nanomedicines: The Tumor Spheroid Penetration Study.
Document Type
Academic Journal
Author
Kudláčová J; Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovskeho nam. 2, 162 06 Prague 6, Czech Republic.; Kotrchová L; Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovskeho nam. 2, 162 06 Prague 6, Czech Republic.; Kostka L; Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovskeho nam. 2, 162 06 Prague 6, Czech Republic.; Randárová E; Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovskeho nam. 2, 162 06 Prague 6, Czech Republic.; Filipová M; Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovskeho nam. 2, 162 06 Prague 6, Czech Republic.; Janoušková O; Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovskeho nam. 2, 162 06 Prague 6, Czech Republic.; Fang J; Faculty of Pharmaceutical Science, Sojo University, Ikeda 4-22-1, Nishi-ku, Kumamoto 860-0082, Japan.; Etrych T; Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovskeho nam. 2, 162 06 Prague 6, Czech Republic.
Source
Publisher: MDPI Country of Publication: Switzerland NLM ID: 101534003 Publication Model: Electronic Cited Medium: Print ISSN: 1999-4923 (Print) Linking ISSN: 19994923 NLM ISO Abbreviation: Pharmaceutics Subsets: PubMed not MEDLINE
Subject
Language
English
ISSN
1999-4923
Abstract
Nanomedicines are a novel class of therapeutics that benefit from the nano dimensions of the drug carrier. These nanosystems are highly advantageous mainly within cancer treatment due to their enhanced tumor accumulation. Monolayer tumor cells frequently used in routine preclinical assessment of nanotherapeutics do not have a spatial structural architecture that allows the investigation of the penetration of nanomedicines to predict their behavior in real tumor tissue. Therefore, tumor spheroids from colon carcinoma C26 cells and glioblastoma U87-MG cells were used as 3D in vitro models to analyze the effect of the inner structure, hydrodynamic size, dispersity, and biodegradability of N -(2-hydroxypropyl)methacrylamide (HPMA) copolymer-based nanomedicines carrying anticancer drug pirarubicin (THP) on the penetration within spheroids. While almost identical penetration through spheroids of linear and star-like copolymers and also their conjugates with THP was observed, THP penetration after nanomedicines application was considerably deeper than for the free THP, thus proving the benefit of polymer carriers. The cytotoxicity of THP-polymer nanomedicines against tumor cell spheroids was almost identical as for the free THP, whereas the 2D cell cytotoxicity of these nanomedicines is usually lower. The nanomedicines thus proved the enhanced efficacy within the more realistic 3D tumor cell spheroid system.