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Chemotherapy for gastric cancer by finely tailoring anti-Her2 anchored dual targeting immunomicelles.
- Source :
-
Biomaterials [Biomaterials] 2012 Jul; Vol. 33 (21), pp. 5349-62. Date of Electronic Publication: 2012 Apr 28. - Publication Year :
- 2012
-
Abstract
- Micelles with high in vivo serum stability and intratumor accumulation post intravenous (i.v.) injection are highly desired for promoting chemotherapy. Herein, we finely synthesized and tailored well-defined anti-Her2 antibody Fab fragment conjugated immunomicelles (FCIMs), which showed interesting dual targeting function. The thermosensitive poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide)(118) (PID(118)) shell with volume phase transition temperature (VPTT: 39 °C) and the anchored anti-Her2 Fab moiety contributed to the passive and active targeting, respectively. The doxorubicin (DOX) loading capacity of such FCIMs was successfully increased about 2 times by physically enhanced hydrophobicity of inner reservoir without structural deformation. The cellular uptake and intracellular accumulation of DOX by temperature regulated passive and antibody navigated active targeting was 4 times of Doxil. The cytotoxicity assay against Her2 overexpression gastric cancer cells (N87s) showed that the IC50 of the FCIMs was ≈ 9 times lower than that of Doxil under cooperatively targeting by Fab at T > VPTT. FCIMs showed high serum stability by increasing the corona PID(118) chain density (S(corona)/N(agg)). In vivo tissue distribution was evaluated in Balb/c nude mice bearing gastric cancer. As observed by the IVIS(®) imaging system, the intratumor accumulation of such finely tailored FCIMs system was obviously promoted 24 h post i.v. administration. Due to the high stability and super-targeting, the in vivo xenografted gastric tumor growth was significantly inhibited with relative tumor volume <2 which was much smaller than ≈ 5 of the control. Consequently, such finely tailored FCIMs with anti-Her2 active and temperature regulated passive dual tumor-targeting function show high potent in chemotherapy.<br /> (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Antineoplastic Agents pharmacology
Antineoplastic Agents therapeutic use
Cell Death drug effects
Cell Line, Tumor
Dialysis
Doxorubicin pharmacology
Doxorubicin therapeutic use
Endocytosis drug effects
Humans
Hydrophobic and Hydrophilic Interactions drug effects
Intracellular Space drug effects
Intracellular Space metabolism
Lactic Acid chemical synthesis
Lactic Acid chemistry
Mice
Mice, Nude
Polyglycolic Acid chemical synthesis
Polyglycolic Acid chemistry
Polylactic Acid-Polyglycolic Acid Copolymer
Reproducibility of Results
Serum metabolism
Solvents
Stomach Neoplasms pathology
Temperature
Tissue Distribution drug effects
Drug Delivery Systems methods
Immunoglobulin Fab Fragments immunology
Micelles
Receptor, ErbB-2 immunology
Stomach Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1878-5905
- Volume :
- 33
- Issue :
- 21
- Database :
- MEDLINE
- Journal :
- Biomaterials
- Publication Type :
- Academic Journal
- Accession number :
- 22542611
- Full Text :
- https://doi.org/10.1016/j.biomaterials.2012.04.016