The effect of blood velocity in solid tumor on intratumorally accumulation and penetration of nanocarriers and drugs

Abstract

Due to the tumor heterogeneity, the velocity of blood flow is significantly different in either various malignancy types or in diversified positioning within a certain tumor. However, despite the nanodrugs administered in a systemic manner are transported into tumors through complicated vessel network, the effects of intratumoral blood velocity on the intratumoral accumulation of nanocarriers and its underlying mechanisms still remain largely unexplored so far. Consequently, we herein constructed several animal models with diverse intratumoral blood velocity via regulating the intratumoral coagulation environment (ICE), and subsequently evaluated the instrumental roles they played on intratumoral accumulation and penetration of nanocarriers and drugs. Interestingly, we discovered when the ICE featured an anti-coagulable state, the blood velocity in tumor vessels was consequently increased, leading to the high frequency of nanocarriers flowing through tumor vessels, improved intratumoral penetration of nanocarriers as well as the promoted intratumoral drug concentrations. On the other hand, when the ICE became a hypercoagulable state, the blood velocity in tumor vessels was prominently decreased correspondingly, generating the low frequency of nanocarriers flowing through tumor vessels and massed retention of nanodrugs in tumor vessels, which increased the number of drugs within tumor as well. Therefore, the evidence indicated that the variation in blood flow velocity caused by modifying ICE have different advantages in improving the efficiency of tumor-targeted nano drugs, which might propose a new perspective to consider how tumor-targeting nanodrugs enter solid tumors and further exert efficacious tumor-killing effectiveness under disparate tumor vascular microenvironment.