Table 2.
Summary of the studies included in the systematic review.
| Author, Year | Objective | Type of Zeolite | Type of Cacer/Tumor | Drug Loaded in Zeolite | Study Type | Cell Line | Model Organism | Conclusions |
|---|---|---|---|---|---|---|---|---|
| Abadeh et al. [14] (2020) | Used a combination of different techniques to investigate the adsorption properties of curcumin by zeolite type A for potential use as an anticancer drug carrier. | Zeolite 5A (LTA) | N/S | curcumin | in vitro | N/A | N/A | Confirmed the presence of curcumin in the zeolite 5A carrier and support the potential use of this porous material as drug carrier in targeted cancer treatments. |
| Martinho et al. [16] (2015) | The effect of zeolites and DDS was evaluated on the viability of glioblastoma cells in comparison with zeolites and temozolomide alone. | Zeolite Y (FAU); mordonite | Glioblastoma | temozolomide | in vitro; in vivo | U251 | fertilized chicken eggs | Zeolite structures can be used effectively for sustained release of temozolomide in glioblastoma cells. |
| Yang et al. [21] (2018) | For the first time fabricated mesoporous ZSM-5 zeolites/chitosan core-shell nanodisks loaded with DOX as DDS against osteosarcoma. | ZSM-5 | Osteosarcoma | DOX | in vitro; in vivo | MG63, hBMSCs | rats | The nanodisk drug carriers efficiently inhibited tumors with minor side effects, especially in cardiac toxicity. |
| Lei et al. [22] (2020) | Grew ZIF-8 on the surface of micelles to form a core-shell nanocomposite for the controlled release of DOX. | ZIF-8 | Breast | DOX | in vitro | MCF-7 | N/A | The core-shell nanocomposite could be a promising candidate for pH-responsive DDS in cancer therapy. |
| Li et al. [25] (2021) | Engineered silk sericin into ZIF-8 to overcome poor circulation stability and unexpected drug leakage into blood circulation, both issues that may limit the benefits of chemotherapy. | ZIF-8 | Mammary | DOX | in vitro; in vivo | 4T1 | mice | The synthesized nanoplatform has tumor-specific biodegradability induced by the low pH environment, efficient drug uptake, and substantial tumor permeability effects. |
| Yan et al. [32] (2020) | Developed a proof of concept methodology for target-specific and pH-responsive delivery of DOX by ZIF-8. | ZIF-8 | Breast | DOX | in vitro; in vivo | MDA-MB-231, MCF-10A | mice | The nanoplatform possesses inherent benefits of more precisely controlling the release of DOX in an acidic tumor microenvironment. |
| Tan et al. [37] (2021) | Reported the DOX-release and cytotoxic properties of DOX/MnO2@ZIF-8 as a chemophotothermal system. | ZIF-8 | Lung | DOX, MnO2 | in vitro; in vivo | LLC | mice | The as-prepared MnO2@ZIF-8 NPs with synergetic therapeutic effects by photothermal therapy and improved tumor microenvironment and as a pH-responsive nanocarrier for delivering the nonspecific anticancer drug DOX might be applied in the treatment of lung cancer. |
| Wu et al. [38] (2018) | Synthesized a biocompatible NIR and pH-responsive drug delivery nanoplatform based on ZIFs (PDA-PCM@ZIF-8/DOX) for in vivo cancer therapy. | ZIF-8 | Liver | DOX | in vitro; in vivo | HepG2 | mice | The biocompatible and biodegradable drug delivery platform based on ZIFs has shown great promise for future clinic cancer therapy. |
| Xie et al. [40] (2020) | Developed a phosphorylcholine-based zwitterionic copolymer coated ZIP-8 nanodrug, and the obtained nanodrug was prepared via a charge-conversional zwitterionic copolymer coating on DOX@ZIF-8 composites. | ZIF-8 | Lung | DOX | in vitro; in vivo | A549 | mice | This nanodrug is shown to have a 93.2% tumor inhibition rate on A549-bearing tumors with negligible side effects, suggesting great potential for this method of improving the efficiency of ZIF-8. |
| Yan et al. [42] (2020) | Loaded a photosensitizer (chlorin e6) and DOX with the ZIF-8 coating layer on E. coli (MG1655) via the biomimetic mineralization method. Subjected to in vitro cell viability assay and in vivo tumor treatment. | ZIF-8 | Breast | DOX, chlorin e6 | in vitro; in vivo | 4T1 | mice | MOF-engineered bacteria are powerful carriers for tumor-targeted therapeutic delivery. |
| Kang et al. [43] (2020) | Developed a convenient strategy and a proof-of-concept multifunctional composite for multimodal imaging and synergistic therapy of cancer using ZIF as a host matrix. | ZIF-8 | Breast | DOX | in vitro; in vivo | 4T1, L929, MCF-7, MCF-10a | mice | Demonstrated an applicable strategy to reveal the highly extendable capacity of ZIF-8 and integrated distinct multiple components in it to fabricate multifunctional composites for highly efficient cancer imaging and therapy. |
| Sharsheeva et al. [44] (2019) | Combined drug delivery nanocomposites with a semiconductor photocatalytic agent that would be capable of inducing a local pH gradient in response to external electromagnetic radiation. | ZIF-8 | Neuroblastoma | DOX | in vitro | IMR-32 | N/A | The system released DOX in a quantity sufficient for effectively suppressing IMR-32 neuroblastoma cells. |
| Shen et al. [45] (2020) | A robust trifunctional polymer coating strategy was proposed to address the major drawbacks of conventional ZIFs, while realizing synergistic chemo-photodynamic treatment by codelivering two therapeutics, chemotherapy drug DOX and near-infrared photosensitizer dye IR780. | ZIF-90 | Cervical | DOX, IR780 | in vitro; in vivo | HeLa | mice | The combined effects of DOX and IR780 not only significantly improved the pH-responsive drug release of ZIF-90, but also facilitated precise drug delivery to CD-44 overexpressed tumors. |
| Wen et al. [46] (2017) | Fabricated hollow mesoporous ZSM-5/chitosan ellipsoids loaded with DOX as pH-responsive drug delivery systems against osteosarcoma. | ZSM-5 | Osteosarcoma | DOX | in vitro; in vivo | hBMSCs, MG63 | rats | The HM-ZSM-5/CS/DOX ellipsoids as novel pH-responsive DDS can effectively treat osteosarcoma without systemic toxicity. |
| Xu et al. [47] (2020) | Aimed to provide a proof of concept for intentionally interfering cellular signaling pathway and autophagy for adjunct chemotherapy. | ZIF-8 | Breast | Rapamycin (Rapa), DOX | in vitro; in vivo | MCF-7/ADR | mice | Rapa@ZIF-8 NPs provide a proof of concept for intentionally interfering cellular signaling pathway for adjunct chemotherapy. |
| Yan et al. [48] (2017) | Proposed a method of employing poly(acrylic acid sodium salt) (PAAS) nanospheres as a soft template to produce size controllable and surface modifiable ZIF 8-poly(acrylic acid sodium salt) nano-composites. | ZIF-8 | Cervical | DOX | in vitro; in vivo | HeLa | mice | The nanocomposites exhibited various crystallinity and pH sensitivity, and retained their therapeutic efficacy when delivering DOX to cell lines and mice models. |
| Zheng et al. [49] (2020) | Presented strong upconversion luminescent biosafe cores derived from LTA and modification with targeted/therapeutic drugs for multimodal therapy, in which sonodynamic therapy (SDT) combined with photodynamic therapy (PDT) increases therapeutic efficiency especially in deep sites of tumor via producing cytoplasmic ROS and mitochondrial superoxide and photothermal therapy (PTT) enhances PDT effects via higher fluorescence resonance energy transfer (FRET) efficacy attributed to an increased temperature. | LTA | Melanoma | DOX | in vitro | B16-F0, 4T1, HBE, U937 | N/A | The multimodal therapy allowed DOX@LTA zeolites to increase its therapeutic efficiency in the deep sites of tumors. |
| Abasian et al. [50] (2019) | Combined magnetic zeolite NaX with PLA/chitosan, Fe3O4, and/or ferrite with or without the presence of a magnetic field for sustained DOX release. | Zeolite NaX (FAU) | Lung | DOX | in vitro | H1355 | N/A | DOX loaded chitosan/PLA/NaX/ferrite with an external magnetic field after 7 days of treatment killed the most H1355 cancer cells (82% cell death) compared to all of the groups. |
| Duan et al. [51] (2018) | Reported a one-pot, rapid, and completely aqueous approach that can precisely tune the size of drug-loaded MOF at room temperature. | ZIF-8 (amorphous) | Breast | DOX | in vitro; in vivo | 4T1 | mice | This size-controlled method helps to find the optimal size of MOF as a drug carrier and opens new possibilities to construct multifunctional delivery systems for cancer theranostics. |
| He et al. [52] (2019) | Examined the control of light and pH on the DOX hydrochloride-releasing properties of Au@ZIF-8. | ZIF-8 | Cervical | DOX hydrochloride | in vitro | HeLa | N/A | Au@ZIF-8 with only 10 μM of DOX hydrochloride can result in 98% HeLa cell-killing activity after 30 min of light irradiation. |
| Khatamian et al. [53] (2016) | Synthesized Zn-Clinoptilolite/GO nanocomposite as an in vitro drug carrier system for DOX. Evaluated its drug loading capacity and studied its cytotoxicity using methyl thiazolyl tetrazolium (MTT) assay. | clinoptilolite | Lung | DOX | in vitro | A549 | N/A | The prepared nanocomposite is cytocompatible and its high loading capacity and slow-release performance for DOX proved that it can be used as a drug carrier. |
| Lv et al. [54] (2019) | Reported the first core−shell multifunctional nanoplatform in the combination of persistent luminescent NPs and MOFs. | ZIF-8 | Breast | DOX | in vitro; in vivo | 4T1 | mice | The loading content of DOX on the nanoplatform reached a high percentage of 93.2%, and the release of DOX was greatly accelerated in the acidic environments created by tumor cells. |
| Zhang et al. [55] (2017) | ZIF-8 is reported for the first time as the multidrug carrier to realizing the efficient co-delivery of verapamil hydrochloride (VER) as the P-glycoprotein inhibitor as well as DOX hydrochloride as an anticancer drug to overcome the MDR in addition to realize the active targeted ability for an efficient anticancer effect. | ZIF-8 | Melanoma, Breast | DOX hydrochloride, Verapamil hydrochloride | in vitro; in vivo | B16F10, MCF-7 | mice | The presented multidrug delivery system can be used as a promising efficient formulation in reversing the multidrug resistance for targeted cancer therapy. |
| Zhao et al. [56] (2019) | Reported the anti-cancer properties of DOX-incorporated persistent luminescent metal-organic framework (PLMOF). | ZIF-8 | Breast | DOX | in vitro; in vivo | 4T1 | mice | The theranostic platform can not only play a critical role in tumor imaging, but also showed anticancer drug loading capacity, acidity-responsive drug release behavior, and significant anti-tumor effect. |
| Zhang et al. [57] (2019) | Explored the combined effects of pH and a NIR laser constructed ZIF-8 Janus NPs with lactobionic acid-gold nanorods on CT image-guided synergistic chemo-photothermal theranostics. | ZIF-8 | Liver; Breast | DOX | in vitro; in vivo | HepG-2; MCF-7 | mice | This dual-stimulation method had advantages in both cancer imaging and inhibited tumors in vivo by releasing pre-loaded DOX. |
| Jiang et al. [59] (2021) | Provided the dependable evidence that aZIFs could improve tumor therapeutic effect in vivo | ZIF-8 (amorphous) | Esophageal | 5-FU | in vitro; in vivo | ECA-109, MCF-7 | mice | aZIF-8 with favorable biocompatibility and long blood circulation is expected to be a promising nano-system for efficacious cancer therapy in vivo. |
| Kulkarni et al. [60] (2021) | The potential of developed nanoplatform against Neuroblastoma was assessed using a cell line studies along with in vivo toxicity studies to ascertain its safety for after in vivo administration in Wistar rats. | ZIF-8 | Neuroblastoma | 5-FU | in vitro; in vivo | IMR-32, SHSY-5Y | rats | Successfully optimized the size and yield of Lf-TC NPs and developed a potential nanoplatform for the multimodal therapy of Neuroblastoma by loading 5-FU inside the ZIF-8 framework. |
| Pandey et al. [61] (2020) | A novel and unique pH responsive nanoplatform have been developed for multimodal therapy of glioblastoma using protein, biopolymer and MOFs. | ZIF-8 | Glioblastoma | 5-FU, zinc | in vitro | U87MG, RAW264.7 | N/A | The results suggest that the nanoplatform is promising for dual drug delivery mediated multimodal therapy of cancer. |
| Vilaca et al. [62] (2013) | Studied the drug delivery properties of FAU (zeolite NaY and zeolite nano NaY) and Linde Type L on colorectal cancer cell lines. | Zeolite NaY (FAU); zeolite nano NaY (FAU), LTL | Colorectal | 5-FU | in vitro | HCT-15, RKO | N/A | Unloaded zeolites presented no toxicity to both cancer cells, while all DDS allowed an important potentiation of the 5-FU effect on the cell viability. |
| Vilaca et al. [63] (2017) | Studied the potential of several silica microporous structures as hosts for 5-FU as DDS for in vitro models of colorectal and breast cancers. | FAU, MFI, LTA | Breast, Colon | 5-FU | in vitro | MDA-MB-468, HCT-15 | N/A | The differing pore sizes of various types of zeolites were demonstrated to have an effect on the loading capacity and release profile of 5-FU. |
| Xiao et al. [64] (2020) | Designed a novel biodegradable treatment system based on ZIF-90. | ZIF-90 | Cervical | 5-FU; ZnO | in vitro; in vivo | HeLa | mice | The 5-FU-ZIF-90@ZnO core-shell NPs are a potential pH-controlled drug release system that can be applied to tumor treatment. |
| Sagir et al. [65] (2016) | Investigated the shapes of the particles, their size, drug loading and releasing capacity and biological activities in gastric cancer cell line AGS. | magnetite–zeolite nanocomposites (MZNC) | Gastric | 5-FU | in vitro | AGS | N/A | 5-FU loaded MZNC efficiently inhibit the proliferation of AGS cells in vitro through apoptotic mechanisms, and may be a beneficial agent against cancer, however further animal study is still required. |
| Cao et al. [66] (2020) | Proposed a structural reconstruction method to effectively explore and improve the biomedical application of ZIFs in esophageal squamous cell cancer theranostics. | ZIF-7 | Esophageal | 5-FU | in vitro; in vivo | K-150, MCF-10A | mice | Incorporating 5-FU into ZIF-7 modified with both metal ions and organic ligands showed a synergistic therapeutic effect in damaging the DNA and inhibiting the chemokine receptor 4 of esophageal squamous cancer cells. |
| Spanakis et al. [67] (2014) | Zeolite particles with different pore diameter and particle size were loaded with 5-FU. The loaded zeolites were characterized by means of SEM, XRD, DSC, XPS, N2 physisorption and FT-IR. | Zeolite NaX (FAU), BEA | N/S | 5-FU | in vitro | N/A | N/A | Higher loading of 5-FU was observed for NaX-FAU than BEA. |
| Abd-Elsatar et al. [68] (2019) | Prepared three types of micronized zeolites and loaded them with 5-FU to be used as delivery systems for oral administration. Tested its efficacy via a cytotoxicity test. | ZSM-5, Zeolite A (LTA), Zeolite NaX (FAU) | Colon | 5-FU | in vitro | CaCo-2 | N/A | The synthesized zeolite frameworks are proposed to be of strong potential drug delivery vehicle for the treatment of gastrointestinal cancer. |
| Zheng et al. [69] (2015) | Developed a straightforward nanoprecipitating method to prepare water dispersible curcumin (CCM)-loaded nanoscale ZIF-8 NPs. | ZIF-8 | Cervical | Curcumin | in vitro; in vivo | HeLa | mice | Both the in vitro and in vivo anticancer experiments indicate that CCM@nZIF-8 has much higher antitumor effect than free CCM and nZIF-8 might be used as the effective drug delivery system for the treatment of carcinoma. |
| Tiwari et al. [70] (2017) | Enlightened a novel approach of single step fabrication of curcumin@ZIF-8 as a drug carrier and its application as stimuli responsive drug delivery systems via external stimuli involving change in pH and in presence of biomimetic cell membrane like environment using liposomes and SDS micelles. | ZIF-8 | Cervical | Curcumin | in vitro | HeLa | N/A | curcumin@ZIF-8 is an efficient drug carrier for passive tumor therapy in future for cancer treatments. |
| Chen et al. [71] (2020) | Constructed a cancer cell membrane-decorated ZIF hybrid nanoparticle (HP) to codeliver cisplatin and oleanolic acid (OLA). | ZIF NPs | Bladder | cisplatin; oleanolic acid (OLA) | in vitro; in vivo | SW780; NIH3T3 | mice | HP/cisplatin/OLA could enhance apoptosis while reverse multidrug resistance in SW780 cells than free drugs alone or monodelivery systems, which might be a suitable DDS for co-delivery of different drugs with great promise. |
| Xing et al. [72] (2020) | Established the significance of the mitochondria-targeting carrier (ZIF-90) in the treatment of platinum-resistant ovarian cancer by a new therapeutic strategy. | ZIF-90 | Ovarian | cisplatin | in vitro | A2780 | N/A | The mitochondria-targeting ZIF-90@DDP with high drug loading could trigger responsive drug release in mitochondria of epithelial ovarian cancer cells, inhibit cisplatin-resistant epithelial ovarian cancer cells, and reverse drug resistance. |
| Salah et al. [73] (2019) | Developed an inorganic-organic hybrid vehicle for the systemic delivery of the tumor suppressor miR-34a. Investigate the efficiency of the delivered miR-34a in the treatment of HCC in vitro and in vivo. | ZSM-5 | Liver | MiR-34a | in vitro; in vivo | HepG2 | mice | Incorporating miR-34a into ZSM-5 showed promising results both in vitro and in vivo by inhibiting target oncogenes such as AEG-1 and SOX-9. |
| Zhao et al. [74] (2021) | Discovered the dual roles of ZIF-8 as nanocarriers for miRNA delivery and adjuvants for chemodynamic therapy. | ZIF-8 | Breast | miR-34a mimic (miR-34a-m) | in vitro; in vivo | MDA-MB-231 | mice | Demonstrated MOFs as a promising nanoplatform for efficient synergetic gene/chemodynamic therapy. |
| Faraji Dizaji et al. [75] (2020) | Various zeolites including hydrophilic Y zeolite, hydrophobic ZSM-5 zeolite and metal organic frameworks (MOFs) including MIL-101 and ZIF-8 were incorporated into the PLGA/chitosan nanofibers for controlled release of Paclitaxel anticancer drug against prostate cancer in vitro and in vivo. | zeolite Y (FAU), ZSM-5, MIL-101, ZIF-8 | Prostate | paclitaxel | in vitro; in vivo | LNCaP | mice | The results confirmed a better performance of anticancer drug loaded-hydrophobic NMOFs loaded-nanofibers compared with zeolites and hydrophilic NMOF loaded-nanofibers for controlled release of anticancer drug and treatment of cancers. |
| Dong et al. [76] (2019) | Constructed a RGD (Arg-Gly-Asp) modified camptothecin@ZIF-8 (RGD@CPT@ZIF-8) as a novel metal-organic frameworks-based hydrophobic DDS for targeted and enhanced cancer treatment. | ZIF-8 | Cervical | camptothecin | in vitro | HeLa | N/A | The nanoplatform exhibited the superior property of target to the cancer cells due to the function with RGD. The RGD@CPT@ZIF-8 nanoplatform has shown the enhanced cancer cell treatment due to the excellent pH-responsive hydrophobic anticancer drug delivery and intracellular ROS generation. |
| Ettlinger et al. [77] (2019) | Developed a pH-responsive nanocarrier of arsenic trioxide based on a metal–organic framework. Studied its drug release kinetics at different pH values and evaluate its cytotoxicity. | ZIF-8 | ATRT | arsenic trioxide | in vitro | ATRT (BT12 and BT16) | N/A | Taking into account the low cytotoxicity of the drug loaded NPs on fibroblast and their cytotoxicity on the selected cancer cell lines, which was comparable to the free drug, ZIF-8 is a very promising candidate for drug delivery of arsenic trioxide. |
| Jia et al. [78] (2019) | ZIF-8 was employed as a carrier for the encapsulation and intracellular delivery of RNase A, aimed to achieve a rapid release of proteins in an acidic environment. | ZIF-8 | Lung | RNase A | in vitro | A549, L02 | N/A | ZIF-8 could be used as an effective carrier to deliver the therapeutic protein RNase A into the cytosol, which will be beneficial for improving the efficacy of cancer treatment. |
| Kamal et al. [79] (2021) | Reported the synthesis and use of nZIF-8 as a nanocarrier that is loaded with gemcitabine and surface-functionalized with the RGD homing peptide ligand to actively-target and specifically-deliver the chemotherapeutic agent to lung cancer cells. | ZIF-8 NPs | Lung | gemcitabine | in vitro | A549, MRC-5 | N/A | Demonstrated a new one-pot strategy for realizing a surface-functionalized zeolitic imidazolate framework that actively targets cancer cells via an autonomous homing peptide system to deliver a chemotherapeutic payload effectively. |
| Li et al. [80] (2018) | Used various techniques, including a transcriptome analysis, to investigate ZIF-8 NPs loaded with melittin, a cytolytic peptide. | ZIF-8 | Lung; cervical | melittin (MLT) | in vitro | A549, HeLa | N/A | There is great potential in using MOFs as a simple and efficient nanoplatform for delivering cytolytic peptides in cancer treatment. |
| Qin et al. [58] (2020) | Presented a facile strategy for constructing a biodegradable nanoparticle of MIP-stabilized fluorescent ZIF-8 for targeted imaging and GSH/pH dual stimulation drug release. | ZIF-8 | Breast, Kidney, Colon | DOX | in vitro; in vivo | MCF-7, LoVo, 293T | mice | Because of the active targeting ability, good biocompatibility, tumor-sensitive biodegradability, and effective drug release performance, FZIF-8/DOX-MIPs can be widely used in tumor imaging and treatment. |
| Zhou et al. [81] (2020) | Hierarchical porous ZIF-8 is fabricated to simultaneously load lactate oxidase (LOD) and Fe3O4 NPs for tumor therapy. | ZIF-8 | Breast | lactate oxidase (LOD), Fe3O4 NPs | in vitro; in vivo | 4T1, MCF-7 | mice | The combined effects of the two compounds is able to provide a simple, safe, and effective method to suppress rapid tumor growth and kill tumor cells. |
| Amorim et al. [82] (2012) | The effect of the zeolites and CHC-loaded zeolite drug-delivery systems were evaluated on HCT-15 human colon carcinoma cell viability. | FAU; Zeolite NaA (LTA) | Colon | α-cyano-4-hydroxycinnamic acid (CHC) | in vitro | HCT-15 | N/A | Both zeolites alone revealed no toxicity to HCT-15 cancer cells. Importantly, CHC@zeolite led to an inhibition of cell viability up to 585-fold when compared to the nonencapsulated drug. |
| Kannen et al. [83] (2020) | Investigated the simultaneous detection of an anticancer drug and a photosensitizer administered in cancer cells using the zeolite matrix to assess their uptakes in cancer cells. | Zeolite NaY (FAU) | Prostate | docetaxel | in vitro | PC-3, PC-3-DR (docetaxel-resistant) | N/A | Indicated the efficacy of photodynamic therapy for docetaxel-resistant cancer cells. |
| Khojaewa et al. [84] (2019) | Searched for a biocompatible mineral carrier that allowed the safe delivery and long-term action of binase needed for treatment of ras-expressing malignances, especially colorectal cancer. | clinoptilolite; chabazite; natrolite | Colorectal | binase | in vitro | Caco2 | N/A | The toxicity of clinoptilolite and chabazite can be enhanced to 57 and 60%, respectively, with the binding and subsequent release of binase. |
| Tomeckova et al. [85] (2012) | Modified clinoptilolite with active pharmaceutical compounds quercetin and quercetin dihydrate and studied their anticancer activities. | clinoptilolite | Leukemia, Cervical, Breast, Lung | Quercetin, quercetin dihydrate | in vitro | Jurkat, CEM, HeLa, MCF-7, A549 and MDA | N/A | Although both drugs showed enhanced cytotoxicity, quercetin dihydrate@clinoptilolite showed greater cytotoxicity than quercetin@clinoptilolite. |
Abbreviations: ZIF = Zeolitic Imidazolate Framework; DDS = Drug Delivery System; LTA = Linde Type A; LTL = Zeolite Type L; 5-FU = 5-fluorouracil; DOX = doxorubicin; FAU = Faujasite; MOF = metal-organic framework; NPs = nanoparticles; MZNC = magnetite zeolite nanocomposite; N/S = Not Specified; N/A = Not Applicable.