Abstract
Nanomedicines including liposomes, micelles, and nanoparticles based on the enhanced permeability and retention (EPR) effect have become the mainstream for tumor treatment owing to their superiority over conventional anticancer agents. Advanced design of nanomedicine including active targeting nanomedicine, tumor-responsive nanomedicine, and optimization of physicochemical properties to enable highly effective delivery of nanomedicine to tumors has further improved their therapeutic benefits. However, these strategies still could not conquer the delivery barriers of a tumor microenvironment such as heterogeneous blood flow, dense extracellular matrix, abundant stroma cells, and high interstitial fluid pressure, which severely impaired vascular transport of nanomedicines, hindered their effective extravasation, and impeded their interstitial transport to realize uniform distribution inside tumors. Therefore, modulation of tumor microenvironment has now emerged as an important strategy to improve nanomedicine delivery to tumors. Here, we review the existing strategies and approaches for tumor microenvironment modulation to improve tumor perfusion for helping more nanomedicines to reach the tumor site, to facilitate nanomedicine extravasation for enhancing transvascular transport, and to improve interstitial transport for optimizing the distribution of nanomedicines. These strategies may provide an avenue for the development of new combination chemotherapeutic regimens and reassessment of previously suboptimal agents.
Highlights
In recent times, nanomedicine delivery to tumors has attracted extensive attention in the field of tumor treatment (Allen and Cullis, 2004; Peer et al, 2007)
The advantage of nanomedicines over free drugs is based on the enhanced permeability and retention (EPR) effect (Fang et al, 2011; Maeda, 2012)
Accumulating evidence revealed that EPRdependent drug delivery was always compromised by the tumor microenvironment including irregular vascular distribution, elevated tumor interstitial fluid pressure (IFP), poor blood flow, rich extracellular matrix (ECM) and abundant tumor stroma cells (Nichols and Bae, 2014)
Summary
Reviewed by: Saraswati Sukumar, School of Medicine, Johns Hopkins University, United States.
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