Abstract
Growth factors and other agents that could potentially enhance tissue regeneration have been identified, but their therapeutic value in clinical medicine has been limited for reasons such as difficulty to maintain bioactivity of locally applied therapeutics in the protease-rich environment of regenerating tissues. Although human diseases are treated with systemically administered drugs in general, all current efforts aimed at enhancing tissue repair with biological drugs have been based on their local application. The systemic administration of growth factors has been ruled out due to concerns about their safety. These concerns are warranted. In addition, only a small proportion of systemically administered drugs reach their intended target. Selective delivery of the drug to the target tissue and use of functional protein domains capable of penetrating cells and tissues could alleviate these problems in certain circumstances. We will present in this review a novel approach utilizing unique molecular fingerprints (“Zip/postal codes”) in the vasculature of regenerating tissues that allows target organ-specific delivery of systemically administered therapeutic molecules by affinity-based physical targeting (using peptides or antibodies as an “address tag”) to injured tissues undergoing repair. The desired outcome of targeted therapies is increased local accumulation and lower systemic concentration of the therapeutic payload. We believe that the physical targeting of systemically administered therapeutic molecules could be rapidly adapted in the field of regenerative medicine.
Highlights
Growth factors and other agents that could potentially enhance tissue regeneration have been identified, but their therapeutic value in clinical medicine has been limited for reasons such as difficulty to maintain bioactivity of locally applied therapeutics in the protease-rich environment of regenerating tissues
Numerous growth factors and other agents that could potentially enhance tissue regeneration have been identified, but their therapeutic application has been rather limited in clinical medicine [1,3,4]
Angiogenesis is driven by tissue hypoxia, and inflammation, as both surviving cells and the inflammatory cells that have invaded the injured area secrete a large number of angiogenic growth factors [1,3,26,27]
Summary
Our increased understanding of the structure of blood vessels on the molecular level has revealed a practical possibility for organ-specific therapeutic treatment of various human diseases with systemically administered drugs [9,14]. Various diseases display disease-specific signatures on the vasculature of the diseased tissue [19]. The disease and organ-specific molecular “Zip codes” in blood vessels can be utilized for target organ-specific delivery of therapeutic molecules by affinity ligands [9,11,14,19]. Affinity-based physical targeting (synaphic, pathotrophic, or active targeting) makes use of these vascular ZIP codes, i.e., molecular markers that are expressed at the target, and not elsewhere in the body, to accomplish selective targeting of systemically administered drugs to the target organ [11]. The desired outcome of the synaphic targeting is increased local accumulation and lower systemic concentration of the therapeutic payload [11]
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