Systemically Administered, Target-Specific, Multi-Functional Therapeutic Recombinant Proteins in Regenerative Medicine.

Tero A H Järvinen,Toini Pemmari

doi:10.3390/nano10020226

Tero A H Järvinen, Toini Pemmari

Open Access

https://doi.org/10.3390/nano10020226

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Journal: Nanomaterials	Publication Date: Jan 28, 2020
Citations: 13	License type: CC BY 4.0

Affiliation: Tampere University Hospital, Tampere University

Abstract

Growth factors, chemokines and cytokines guide tissue regeneration after injuries. However, their applications as recombinant proteins are almost non-existent due to the difficulty of maintaining their bioactivity in the protease-rich milieu of injured tissues in humans. Safety concerns have ruled out their systemic administration. The vascular system provides a natural platform for circumvent the limitations of the local delivery of protein-based therapeutics. Tissue selectivity in drug accumulation can be obtained as organ-specific molecular signatures exist in the blood vessels in each tissue, essentially forming a postal code system (“vascular zip codes”) within the vasculature. These target-specific “vascular zip codes” can be exploited in regenerative medicine as the angiogenic blood vessels in the regenerating tissues have a unique molecular signature. The identification of vascular homing peptides capable of finding these unique “vascular zip codes” after their systemic administration provides an appealing opportunity for the target-specific delivery of therapeutics to tissue injuries. Therapeutic proteins can be “packaged” together with homing peptides by expressing them as multi-functional recombinant proteins. These multi-functional recombinant proteins provide an example how molecular engineering gives to a compound an ability to home to regenerating tissue and enhance its therapeutic potential. Regenerative medicine has been dominated by the locally applied therapeutic approaches despite these therapies are not moving to clinical medicine with success. There might be a time to change the paradigm towards systemically administered, target organ-specific therapeutic molecules in future drug discovery and development for regenerative medicine.

Highlights

Intensive research during the past few decades has led to the identification of the key molecules, growth factors, cytokines and chemokines, for tissue regeneration after injuries [1,2]
Systemic drug administration of both recombinant proteins and conventional drugs is the only drug delivery mode used for the vast majority of human diseases, systemic administration has not been considered as a viable option in the treatment of tissue injuries due to the lack of efficiency and safety
The blood vessels in each tissue have molecular structures (“molecular fingerprint”) on their lumen that are unique for the given tissue, essentially forming a system that is very similar to postal codes in society (“vascular zip codes”) [19,20] (Figure 1)

Summary

Introduction

Intensive research during the past few decades has led to the identification of the key molecules, growth factors, cytokines and chemokines, for tissue regeneration after injuries [1,2]. Target organ-specific drug delivery obtained by the combination of vascular homing peptides and functional protein domains, such as cell penetrating peptides proficient in penetrating cells and tissues, could solve these problems.

Results

Conclusion