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.