Proteolytic Enzymes and Cavitation as Strategies to Enhanced Penetration of Drug Nanocarriers

Since Matsummura & Maeda [1] discovered the tendency of nanocarriers to be extravasated and accumulated in tumoral tissues, nanomedicine has emerged as a promising alternative to conventional cancer therapies. This effect receives the name of Enhanced Permeability and Retention (EPR) effect and is due to the irregular vasculature that irrigated the solid tumor, which present fenestrations of hundreds of nanometers [2]. This high porosity allows that nanocarriers be selectively accumulated into the diseased tissue. In addition, the high interstitial pressure [3,4] caused by the deficient lymphatic drainage, favors their retention. However, to reach and to be accumulated into the malignant tissue is only the first step which a nanocarrier must overcome. Once there, they should be capable to achieve a homogeneous distribution within the diseased tissue in order to lead to an effective treatment. Unfortunately, the elevated interstitial pressure and high collagen content [5] in the ECM suppose a great impediment to their diffusion and provoke that the nanocarriers remain localized in the periphery of the malignancy, which strongly limits their efficacy.