Intrinsically active nanobody-modified polymeric micelles for tumor-targeted combination therapy

Abstract Various different passively and actively targeted nanomedicines have been designed and evaluated over the years, in particular for the treatment of cancer. Reasoning that the potential of ligand-modified nanomedicines can be substantially improved if intrinsically active targeting moieties...

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Bibliographic Details
Published in:Biomaterials 2013-01, Vol.34 (4), p.1255-1260
Main Authors: Talelli, Marina, Oliveira, Sabrina, Rijcken, Cristianne J.F, Pieters, Ebel H.E, Etrych, Tomas, Ulbrich, Karel, van Nostrum, Rene C.F, Storm, Gert, Hennink, Wim E, Lammers, Twan
Format: Article
Language:English
Subjects:
Active targeting
Advanced Basic Science
Animals
Biomaterials
Biomedical materials
Cancer
Dentistry
Diffusion
Doxorubicin
Doxorubicin - administration & dosage
Doxorubicin - chemistry
Drug Combinations
Drugs
Effectiveness
EGFR
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Micelle
Micelles
Nanobody
Nanocapsules - administration & dosage
Nanocapsules - chemistry
Nanomedicine
Nanostructure
Neoplasms, Experimental - drug therapy
Neoplasms, Experimental - pathology
Polymers - chemistry
Surgical implants
Therapy
Treatment Outcome
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Summary:Abstract Various different passively and actively targeted nanomedicines have been designed and evaluated over the years, in particular for the treatment of cancer. Reasoning that the potential of ligand-modified nanomedicines can be substantially improved if intrinsically active targeting moieties are used, we have here set out to assess the in vivo efficacy of nanobody-modified core-crosslinked polymeric micelles containing covalently entrapped doxorubicin. Nanobody-modified polymeric micelles were found to inhibit tumor growth even in the absence of a drug, and nanobody-modified micelles containing doxorubicin were significantly more effective than nanobody-free micelles containing doxorubicin. Based on these findings, we propose that the combination of two therapeutic strategies within one nanomedicine formulation, i.e. the intrinsic pharmacological activity of ligand-modified carrier materials with the cytostatic activity of the incorporated chemotherapeutic agents, is a highly promising approach for improving the efficacy of tumor-targeted combination therapy.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2012.09.064