Pressure-induced amorphous zeolitic imidazole frameworks with reduced toxicity and increased tumor accumulation improves therapeutic efficacy In vivo.

ABSTRACT: Zeolitic Imidazole Frameworks (ZIFs) are widely applied in nanomedicine for their high drug loading, suitable pore size, pH-responsive drug release, and so on. However, fast drug release during circulation, unexpected toxicity to mice major organs, undesirable long-term accumulation in the lung and even death currently hinder their in vivo biomedical applications. Herein, we report an amorphous ZIF-8 (aZIF-8) with high loading of 5-Fu through pressure-induced amorphization. This nano-system avoids early drug release during circulation and provides tumor microenvironment-responsive drug release with improved in vitro cell viability, and survival rate in in vivo evaluations as compared to ZIF-8. Furthermore, aZIF-8 shows longer blood circulation and lower lung accumulation than ZIF-8 at same injected doses. Less drug release during circulation, longer blood circulation, and better biocompatibility of aZIF-8/5-Fu significantly improves its therapeutic efficacy in ECA-109 tumor-bearing mouse, and result in 100% survival rate over 50 days after treatment. Therefore, aZIF-8 with favorable biocompatibility and long blood circulation is expected to be a promising nano-system for efficacious cancer therapy in vivo.

SUBMITTER: Jiang Z 

PROVIDER: S-EPMC7519214 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature