title: 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 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.
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: Marina
authors.initials: M
authors.lastname: Talelli
authors.forename: Sabrina
authors.initials: S
authors.lastname: Oliveira
authors.forename: Cristianne J F
authors.initials: CJ
authors.lastname: Rijcken
authors.forename: Ebel H E
authors.initials: EH
authors.lastname: Pieters
authors.forename: Tomas
authors.initials: T
authors.lastname: Etrych
authors.forename: Karel
authors.initials: K
authors.lastname: Ulbrich
authors.forename: Rene C F
authors.initials: RC
authors.lastname: van Nostrum
authors.forename: Gert
authors.initials: G
authors.lastname: Storm
authors.forename: Wim E
authors.initials: WE
authors.lastname: Hennink
authors.forename: Twan
authors.initials: T
authors.lastname: Lammers
mesh_terms: D000818:Animals; D004058:Diffusion; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D004338:Drug Combinations; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008823:Micelles; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry*; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology*; D011108:Polymers / Q000737:chemistry*; D016896:Treatment Outcome
chemical_list: D004338:Drug Combinations; D008823:Micelles; D053769:Nanocapsules; D011108:Polymers; D004317:Doxorubicin