Extracellular Matrix Degrading Enzymes for Nanocarrier-Based Anticancer Therapy

Abstract

Perfusion is seriously hampered in solid tumors that overexpress extracellular matrix components like hyaluronic acid, collagen and chondroitin sulfate. Tumor penetration of circulating material is most affected for nanocarriers because of their size and lower diffusion. Due to this, the aid of enzymes that degrade the matrix becomes essential when applying nanocarrier based anticancer therapies like oncolytic viruses or nano-formulated drugs like Abraxane or Doxil. In the case of hyaluronic acid and chondroitin sulfate, these biomacromolecules bind water very tightly and as a consequence of this, tumors that abound in them have an elevated resistance to a contacting fluid. In the case of collagen, the dense molecular network represents a physical barrier for any nanocarrier and also compresses the tumor vessels obstructing perfusion. Drug penetration and therapeutic index increase when anticancer therapies are combined with enzymes that specifically degrade the over-expressed matrix component. This chapter will cover the use of matrix degrading enzymes for enhancing the delivery of nanocarriers, including oncolytic viruses and synthetic nanoparticles. Ongoing clinical trials will be discussed.