Coordination conjugates of therapeutic proteins with drug carriers: A new approach for versatile advanced drug delivery

We present here a general system for the coordination attachment of therapeutic proteins to a drug delivery system and its application in combined therapy. Proof of concept is demonstrated by the synthesis and testing of the targeted drug delivery system for cytostatics, which is based on a combinat...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2011-09, Vol.21 (18), p.5514-5520
Main Authors: KEJIK, Zdeněk, BRIZA, Tomas, KRALOVA, Jarmila, POUCKOVA, Pavla, KRAL, Aleš, MARTASEK, Pavel, KRAL, Vladimir
Format: Article
Language:English
Subjects:
animal models
Animals
Antineoplastic agents
Biological and medical sciences
biopharmaceuticals
carcinoma
chemotherapy
Combined cancer therapy
Combined treatments (chemotherapy of immunotherapy associated with an other treatment)
coordination compounds
Cyclodextrins - chemistry
Cytostatic Agents - chemistry
Cytostatic Agents - therapeutic use
Cytostatics
Disease Models, Animal
drug carriers
Drug Carriers - chemistry
Drug Delivery Systems
Humans
immunoglobulins
Immunoglobulins - chemistry
immunotherapy
lectins
Medical sciences
Melanoma, Experimental - drug therapy
Melanoma, Experimental - immunology
Metalloporphyrins - chemistry
Mice
Mice, Nude
Molecular Conformation
Pharmacology. Drug treatments
Photodynamic therapy
Targeted drug delivery
Therapeutic proteins
Zinc - chemistry
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Summary:We present here a general system for the coordination attachment of therapeutic proteins to a drug delivery system and its application in combined therapy. Proof of concept is demonstrated by the synthesis and testing of the targeted drug delivery system for cytostatics, which is based on a combination of the drug carrier Zn–porphyrin–cyclodextrin conjugates and their supramolecular coordination complexes with immunoglobulins. This system can be as readily used for a variety of therapeutic and targeting proteins including PAs, MAs, lectins, and HSA. Moreover, it allows combined photodynamic therapy, cell targeted chemotherapy and immunotherapy. When tested in a mouse model with human C32 carcinoma, the therapeutic superiority of the coordination assembly nanosystem was shown in comparison with the efficacy of building blocks used for the construction of the system.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2011.06.101