A novel structure of ultra-high-loading small molecules-encapsulated ZIF-8 colloid particles

The safety of nanoparticle-based drug delivery systems (DDSs) for cancer treatment is still a challenge, restricted by the intrinsic cytotoxicity of drug carriers and leakage of loaded drug. Here, we propose a novel nanocarrier’s cytotoxicity avoidance strategy by synthesizing an encapsulation core–shell structure of zeolitic imidazolate framework-8 (ZIF-8)-based colloid particles (CPs) with an amorphous ZIF-8 skin. This encapsulation structure achieves an ultra-high loading rate (LR) of 90% (i.e., 9 mg doxorubicin (DOX) per 1 mg ZIF-8) for DOX and the protection of DOX from leaking. Notably, to deliver unit-dose drug, this ultra-high LR of 90% significantly reduces the usage of ZIF-8 to 1.2% (2 orders of magnitude) compared to that of DOX@ZIF-8 with a 10% LR, in which cytotoxicity of ZIF-8 could well below the safety limit and then be relatively ignored. Safety, drug delivery efficacy, scale-up ability, and universality of this encapsulation structure have been further verified. Our findings suggest the great potential of this ZIF-8-based encapsulation core–shell structure in the field of drug delivery.