Response and Regulation of the Microenvironment Based on Hollow Structured Drug Delivery Systems

Abstract Hollow structured materials with easily modifiable surfaces and enclosed interior spaces have emerged as the most promising candidates in drug delivery systems (DDS). With various functional components and inspiring cavities for creative reinvention, the response and regulation of the external and internal microenvironment of hollow structures enable their ideal drug delivery capabilities by improving drug aggregation in targeted sites and maintaining plasma concentrations at the optimal therapeutic ranges. This review begins with an in‐depth explanation of the interactions and release mechanisms of hollow structure‐based DDS, including diffusion, assembly, solvent activation, and chemical control, all of which are of great significance for the design of smart drug carriers. Next, recent advances in external microenvironment‐responsive drug delivery systems are introduced, based on various chemical signals and external field assists. Focusing on the unique view of intra‐carrier variability, the strategies for regulating the internal environment are then highlighted, including pH regulation, temperature regulation, and mechanical force regulation. Finally, this review discusses possible challenges and prospects for hollow structure‐based, particularly hollow multishelled structures intelligence‐responsive drug delivery platforms, providing valuable strategies for the development of the next generation of responsive DDS.