Using Properties of Tumor Microenvironments for Controlling Local, On-Demand Delivery from Biopolymer-Based Nanocarriers

Background: The 'tumor microenvironment' comprised of tumor cells, non-malignant stromal tissues, signaling molecules and the extracellular matrix. Tumor microenvironment has unique physical and physiological characteristics including vascular abnormalities, hypoxia, acidic pH, specific enzymes and growth factors upregulation and high reducing potential. It is these endogenous properties of the tumor environment that can be used to trigger the release of cancer therapeutics both locally and as a function of disease state. Biopolymers such as proteins, polypeptides and polysaccharides are actively being designed to be bioresponsive nanocarriers for drug delivery due to their relative biocompatibility, biodegradability and low immunogenicity. Objective: This review focuses on the use of physicochemical attributes of the endogenous tumor microenvironment to provide the impetus for on-demand release of therapeutics from biopolymer-based nanocarriers that are sensitive to pH, enzymes, redox conditions and combinations thereof. Conclusion: The development of multifunctional nanocarriers based upon a rational approach for targeting and delivering therapeutics to tumors is an area of active research. Despite the huge amount of work done in this area, especially using pH as a means of eliciting drug release at tumor sites, there is a dearth of work whereby different stages during tumor development are targeted for treatment. Although nanocarriers that are able to react to multiple components of the tumor microenvironment are starting to become common-place, it seems that the ability to release various factors at specific times crucial to therapy has not been studied to a large extent as a means of regaining tissue homeostasis.