A stable biocompatible porous coordination cage promotes in vivo liver tumor inhibition

Abstract

Many emerging strategies in chemo-, gene-, and immunotherapy require the accumulation of reagents in the cell nucleus. However, their delivery into the nucleus is often limited. Nuclear delivery could be enhanced with a rationally designed cargo-delivery scaffold, but this approach has rarely been successfully implemented. Herein, a stable, biocompatible molecular capsule that encapsulates and delivers camptothecin, a DNA topoisomerase I inhibitor, into the nucleus of living cells was reported. Nuclear delivery is facilitated by the ultra-small diameter, zero net charge, and hydrophobicity of the capsule. The encapsulated drug complex displays superior toxicity towards multiple cancer cells over the free drug, the Food and Drug Administration (FDA) approved drugs, as well as conventionally reported drug vectors. Additionally, it inhibits liver cancer tumor growth in a xenograft mouse model. Modification of the properties of such molecular capsules may make it possible to design therapeutic strategies that target specific cell organelles.

Modeling the Enzyme Specificity by Molecular Cages through Regulating Reactive Oxygen Species Evolution

“…PCC‐6‐M (M=Zn, Co, Ni) was synthesized by a solvothermal approach (Section S3, Supporting Information). PCC‐6‐Zn was formed by the reaction of the vertex ligand (H 4 TBSC, p ‐ tert ‐butylsulfonylcalix[4]arene) and panel ligand (H 3 L, PTH‐COOH) with ZnCl 2 at 130 °C in N,N‐dimethylformamide (DMF) for 48 h. PCC‐6‐Co was obtained with the same procedure as PCC‐6‐Zn with CoCl 2 instead of ZnCl 2 [22] . PCC‐6‐Ni was prepared by using nickel perchlorate as the nickel source, and the reaction time was reduced to 24 h while the amount of DMF was increased.…”

Organo-macrocycle-containing hierarchical metal–organic frameworks and cages: design, structures, and applications

“…40). 195 It was found that CA-PCC 35 is capable of transporting to the cell nucleus and achieving targeted delivery of anti-cancer drugs, dramatically improving the anti-cancer efficacy in vitro . Then, when a liver-cancer-tumor grafted mouse model was used for in vivo study, the drug complex CPT@35 could inhibit tumor growth without damaging other healthy organs in the living mouse.…”

Porous Framework Materials for Bioimaging and Cancer Therapy

“…Herein, we present the recent advances in metal-organic frameworks (MOFs) [ 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ], covalent organic frameworks (COFs) [ 44 , 45 , 46 , 47 , 48 , 49 ], and porous coordination cages (PCCs) [ 50 , 51 , 52 ] for cancer therapy, mainly in bioimaging, and treatments using photothermal therapy, thermodynamic therapy, or a combination of different therapies in cancer therapy ( Scheme 1 ). We highlight the applications of porous framework materials for bioimaging and cancer therapy in this article ( Table 1 ).…”