ZnO-Based Nanoparticles for Targeted Cancer Chemotherapy and the Role of Tumor Microenvironment: A Systematic Review
Abstract
Cancer, a leading global cause of death responsible for nearly 10 million deaths annually, demands innovative therapeutic strategies. Intrinsic cytotoxicity and biocompatibility of zinc oxide nanoparticles (ZnO-NPs) have rendered them promising nanoplatforms in oncology. We herein systematically review their applications for targeted cancer chemotherapy, with a focus on physicochemical properties, drug delivery mechanisms, and interactions with the tumor microenvironment (TME). We searched PubMed, SCOPUS, and Web of Science from inception through December 2024 for peer-reviewed preclinical studies on cancer models. Results were qualitatively synthesized. Quality was assessed with the SYRCLE risk of bias tool. Among 20 eligible studies, ZnO-NPs were frequently functionalized with ligands to enhance tumor targeting and minimize systemic toxicity. Chemotherapeutic agents (doxorubicin, 5-fluorouracil, docetaxel, cisplatin, gemcitabine, and tirapazamine) were loaded into ZnO-based carriers, with improved anticancer efficacy compared to free drug formulations, particularly in multidrug-resistant cell lines and in vivo murine xenografts. The mildly acidic TME was exploited for pH-responsive drug release, premature leakage reduction, and improvement of intratumoral accumulation. Enhanced therapeutic outcomes were attributed to reactive oxygen species generation, zinc ion-mediated cytotoxicity, mitochondrial dysfunction, and efflux pump inhibition. Deep tumor penetration, apoptosis…
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Evidence Hub reads this as a systematic review, done in animal, not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
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