Design strategies for enhancing antitumor efficacy through tumor microenvironment exploitation using albumin-based nanosystems: A review

The tumor microenvironment (TME) is a complex and dynamic system that plays a crucial role in regulating cancer progression, treatment response, and the emergence of acquired resistance mechanisms. The TME is usually featured by severe hypoxia, low pH values, high hydrogen peroxide (H2O2) concentrations, and overproduction of glutathione (GSH). The current development of intelligent nanosystems that respond to TME has shown great potential to enhance the efficacy of cancer treatment. As one of the functional macromolecules explored in this field, albumin-based nanocarriers, known for their inherent biocompatibility, serves as a cornerstone for constructing diverse therapeutic platforms. In this paper, we present a comprehensive overview of the latest advancements in the design strategies of albumin nanosystems, aiming to enhance cancer therapy by harnessing various features of solid tumors, including tumor hypoxia, acidic pH, the condensed extracellular matrix (ECM) network, excessive GSH, high glucose levels, and tumor immune microenvironment. Furthermore, we highlight representative designs of albumin-based nanoplatforms by exploiting the TME that enhance a broad range of cancer therapies, such as chemotherapy, phototherapy, radiotherapy, immunotherapy, and other tumor therapies. Finally, we discuss the existing challenges and future prospects in direction of albumin-based nanosystems for the practical applications in advancing enhanced cancer treatments.