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 .

Effects of Zeolite as a Drug Delivery System on Cancer Therapy: A Systematic Review

“…Through the literature search, it was determined that there is great heterogeneity in the experimental methods and conditions between studies reporting on zeolites/ZIFs as anticancer drug delivery systems. The most common anticancer drug loaded were doxorubicin (DOX) [ 21 , 22 , 25 , 32 , 37 , 38 , 40 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 ], 5-fluorouracil (5-FU) [ 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 ], curcumin [ 14 , 69 , 70 ], cisplatin [ 71 , 72 ], and miR-34a [ 73 , 74 ]. The articles also employed a variety of both ZIFs and natural/synthetic zeolites ( Table 1 ).…”

“…The articles also employed a variety of both ZIFs and natural/synthetic zeolites ( Table 1 ). Of the 53 articles included in this study, 36 studies utilized ZIFs [ 22 , 25 , 30 , 32 , 37 , 38 , 40 , 42 , 43 , 44 , 47 , 48 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 64 , 66 , 70 , 71 , 72 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 ], 9 studies utilized faujasite (FAU) [ 16 , 50 , 62 , 64 , 67 , 68 , 75 , 82 , 83 ], 5 studies utilized Zeolite A/Linde Type A (LTA) [ 14 , 49 , 63 , 68 , 82 ], and 3 studies utilized clinoptilolite [ 53 , 8...…”

“…In addition, Jiang et al utilized pressure-induced amorphization to load a large amount of 5-FU into amorphous ZIF-8. Amorphous ZIF-8/5-FU was shown to have significant therapeutic efficacy in tumor-bearing mice due to less drug released during circulation, longer circulation time, and great biocompatibility [ 59 ]. Furthermore, Kulkarni et al characterized 5-FU in the ZIF-8 framework using techniques such as FTIR, PXRD, Raman spectroscopy, EDX, and UV-NIR spectroscopy as well as morphological techniques such as SEM, TEM, and AFM [ 60 ].…”

Chemotherapeutic nanomaterials in tumor boundary delineation: Prospects for effective tumor treatment

“…As regards tumor chemotherapy in general, research in our laboratories on tumor-targeted chemotherapeutic nanomaterials have also contributed a great deal to recent advances on tumor chemotherapy. Specifically, interesting nanomaterial-based drug delivery systems with excellent biocompatibility and tumor microenvironment responsiveness have been developed in our research group including doxorubicin (DOX)-loaded zeolitic imidazole framework (ZIF) nanomaterials with pH-responsiveness 14 , cisplatin-loaded ZIF nanomaterials with mitochondrial targeting in platinum-resistant ovarian tumor 15 , and 5-fuorouracil-loaded amorphous ZIF nanomaterials with high drug-loading and tumor microenvironment responsiveness 16 . Such nanomaterials demonstrated appreciable capability to deliver substantial amounts of chemotherapeutic drugs to tumor sites for achieving meaningful tumor regression.…”

Recent Advance in Biological Responsive Nanomaterials for Biosensing and Molecular Imaging Application

“…As porous materials comprising organic ligands and metal ions or clusters, metalorganic frameworks (MOFs) involve self-assembly through coordination bonding. MOF materials are available in a wide range of shapes and sizes, with high porosity, tunable pores, and specific surface area, and can be used in various applications, including energy storage and catalysis [52,53]. In contrast to typical porous materials, nanoscale metal-organic frameworks (NMOFs) have huge surface areas, adjustable pore sizes, and well-defined crystalline structures [54][55][56][57].…”