Targeting cancer cells in the tumor microenvironment: opportunities and challenges in combinatorial nanomedicine.

Cancer therapies of the future will rely on synergy between drugs delivered in combination to achieve both maximum efficacy and decreased toxicity. Nanoscale drug delivery vehicles composed of highly tunable nanomaterials ('nanocarriers') represent the most promising approach to achieve simultaneous, cell-selective delivery of synergistic ratios of combinations of drugs within solid tumors. Nanocarriers are currently being used to co-encapsulate and deliver synergistic ratios of multiple anticancer drugs to target cells within solid tumors. Investigators exploit the unique environment associated with solid tumors, termed the tumor microenvironment (TME), to make 'smart' nanocarriers. These sophisticated nanocarriers exploit the pathological conditions in the TME, thereby creating highly targeted nanocarriers that release their drug payload in a spatially and temporally controlled manner. The translational and commercial potential of nanocarrier-based combinatorial nanomedicines in cancer therapy is now a reality as several companies have initiated human clinical trials.