Key Tumor Responsive ZIF-8 Nanocarriers for Effective Anti-Cancer Therapeutics

The intricate pathological features of the tumor microenvironment (TME) collectively contribute to therapeutic resistance, thereby substantially constraining the antitumor efficacy of conventional treatments. Zeolitic imidazolate framework-8 (ZIF-8), a pH-responsive metal-organic framework material, serves not only as an efficient drug delivery system but also actively participates in TME remodeling through the release of Zn²⁺ upon its degradation. This dual function as both a "carrier" and an "effector" offers a synergistic mechanism to mitigate therapeutic resistance. The article reviews recent research on ZIF-8, focusing on its role in targeted drug delivery and its transformation from a passive carrier to an active modulator of cellular environments. It examines how ZIF-8's synthetic pathways and surface modifications aid in delivering various drugs and analyzes the molecular mechanisms by which released Zn²⁺ triggers stress responses and immune reactions. The article also discusses ZIF-8's integration into theranostic platforms, its use in combination therapies, and the clinical translation challenges, including biosafety, reproducibility, and scalable production. This review aims to systematically synthesize existing knowledge across the aforementioned fields to establish a theoretical foundation for the design of next-generation ZIF-8 nanotheranostic systems and facilitate their progression toward clinical translation.