High Biocompatible ZIF-8 Coated by ZrO₂ for Chemo-microwave Thermal Tumor Synergistic Therapy

Abstract

The zeolitic imidazolate framework-8 (ZIF-8) is a specifically promising drug carrier due to its excellent intrinsic properties. However, the high toxicity of ZIF-8 nanoparticles severely limits their further research and clinical application. In this work, the biocompatibility of ZIF-8 nanoparticles is greatly improved by coating ZrO 2 onto the surface. The survival rate of cells and mice in the ZIF-8@ZrO 2 nanocomposite group is significantly increased compared with the undecorated ZIF-8 nanoparticle group. Doxorubicin (DOX) as a chemotherapeutic drug is deposited during the ZIF-8 growth by a facile one-pot method. Ionic liquid (IL) is loaded into the pore of the ZIF-8/DOX@ZrO 2 nanocomposites for enhancing microwave thermal therapy. The tumor inhibition rate of ZIF-8/DOX@ZrO 2 @IL nanocomposites with synergistic microwave thermal therapy and chemotherapy is obviously higher than in other groups. In addition, the ZIF-8/DOX@ZrO 2 @IL nanocomposites are used for real-time monitoring of the therapeutic outcomes due to the excellent computed tomography contrast agent, ZrO 2 . Therefore, such a ZrO 2 coating strategy shows great promise for overcoming high toxicity of ZIF-8 nanoparticles, which offers a new platform for tumor synergistic microwave thermal therapy and chemotherapy using the ZIF-8/DOX@ZrO 2 @IL nanocomposite as a theranostic nanocarrier.

Synthesis and modification of ZIF-8 and its application in drug delivery and tumor therapy

“…Photothermal therapy (PTT) is a minimally invasive local therapy, which uses photothermal conversion agents (such as gold nanoparticles, graphene, ionic liquids, and near-infrared dyes) to generate heat at the tumor site to inhibit the growth of tumors or promote cancer cell apoptosis. [95][96][97] Gold nanoparticles have good biocompatibility, high photothermal conversion efficiency, and unique near-infrared (NIR) optical absorption properties. 94 Li et al coated ZIF-8 on gold nanorods (Au NR) to prepare AuNR@ZIF-8 core/shell nanostructure nanomaterials.…”

“…In addition, since ZrO 2 is also an excellent computed tomography (CT) contrast agent, ZIF-8/DOX@ZrO 2 @IL nanocomposites can also be used to monitor therapy results in real time. 96 When encapsulating drugs in situ during the synthesis of MOFs, only limited drug molecules (such as camptothecin, doxorubicin, caffeine) with special functional groups (-COOH, -SO 3 H) or opposite charges can successfully interact with MOFs to realize in situ packaging. 97 Zhang et al proposed a prodrug strategy to solve the problem of drug encapsulation difficulties.…”

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

“…However, many undesirable outcomes still hamper the in vivo application of ZIFs in biomedicine, such as fast drug release during circulation [ 7 , 10 ], unexpected toxicity to mice major organs [ 16 ], undesirable long-term accumulation in the lung [ 10 ], and even death. Some researchers have explored surface modification [ 16 ], metal-oxide coating [ 17 ], etc., as strategies to ameliorate these side effects. Although such strategies serve to improve the biocompatibility and expand in vivo applications of ZIF-8, drug loading rates and pH-responsive abilities are consequently compromised.…”

Mineralization of pH-Sensitive Doxorubicin Prodrug in ZIF-8 to Enable Targeted Delivery to Solid Tumors

“…Therefore, the doses must be limited. 14 , 20 , 21 Moreover, many other MOF candidates have suffered from similar drawbacks in biomedical applications.…”

“…To overcome these problems, different strategies have been investigated to improve the ZIF-8 system, such as surface coating by ZrO 2 or polydopamine to decrease the ZIF-8 toxicity 20 and carbonating ZIF-8 at 800 °C and then reacting it with (NH 4 ) 2 S 2 O 8 and concentrated H 2 SO 4 to achieve surface carboxylation for postmodification. 22 However, these methods are complicated and need harsh reaction conditions; hence, they are difficult to scale up.…”