Navigating tumor microenvironment with TME-responsive nanocarriers: Strategies for targeted drug delivery in solid tumor

Solid tumors exhibit complex tumor microenvironments, with characteristic features like hypoxia, acidic pH, increased enzyme levels, and altered redox levels. The heterogeneous nature of tumor microenvironments across different tumors limits the broader applicability of receptor-based nanotherapy. However, the tumor microenvironment of most solid tumors exhibits common features, and nanocarriers responding to these unique features have shown great promise in recent years. These nanocarriers are typically engineered to travel through the bloodstream, localize at tumor locations, and then carry out their functions within the tumor environment. Such nanocarriers remain inactive throughout blood circulation, but once they are localized in solid tumors by exploiting leaky vasculature, nanocarriers show a drastic change in their structure to release encapsulated payloads in response to characteristic features of the tumor microenvironment, involving elevated redox or enzyme levels, hypoxia, and a decreased pH. Owing to the site-specific delivery of tumor microenvironmentresponsive nanocarriers, the off-target side effects associated with conventional chemotherapy can be minimized. By integrating various stimuli-responsive features, these specialized nanoplatforms can overcome tumor heterogeneity and improve drug localization, thereby addressing significant limitations of current cancer therapies. The present review offers a concise exploration of the tumor microenvironment, followed by its unique features and nanocarrier-based strategies to selectively deliver bioactives in the vicinity of solid tumors.