Abstract
The tumor microenvironment (TME) is a dynamic, complex milieu that includes cancer cells, stromal cells, immune cells, components of the extracellular matrix, and a network of signaling molecules that interact to drive tumor progression, immune evasion, and therapy resistance. The lack of specific tumor targeting and the presence of non-specific toxicity and poor tumor penetration make conventional cancer therapies (including chemotherapy and radiation) less effective and more urgent than ever before. Within the last twenty years, nanotechnology has become a revolutionary platform for treating cancer and has offered unprecedented control over drug delivery, tumor targeting, and on-demand release of therapeutics in response to TME-specific stimuli. This review gives an overview of the landscape of TME and discusses how several nanotechnology-based approaches, including liposomes, polymeric nanoparticles, inorganic nanocarriers, exosomes and hybrid nanostructures, are being engineered to take advantage of the characteristics of TME, including hypoxia, acidic pH, elevated reactive oxygen species, and aberrant enzyme expression. We also discuss the functions of active and passive targeting, stimuli-responsive drug delivery, immunomodulatory nanomedicine, and combination therapy strategies in overcoming TME-mediated drug resistance. Also, clinical translation issues, regulatory issues, and prospective issues are discussed. Collectively, this review indicates the enormous potential of nanotechnology as a precision-medicine modulator for redefining the TME and enhancing the effectiveness of cancer treatment.