Preclinical developments of natural-occurring halloysite clay nanotubes in cancer therapeutics

The natural world holds useful resources that can be exploited to design effective therapeutic approaches. Ready-to-use tubular nanoclays, such as halloysite clay nanotubes (HNTs), are widely available, cost-effective, and sustainable submicron crystalline materials that have been showing great potential towards chronic multifactorial and malignant diseases, standing out as a promising anticancer nanotherapeutic strategy. Currently, several preclinical studies have reported the application of HNTs in cancer research, diagnosis, monitoring, and therapeutics. This groundbreaking review highlights the preclinical knowledge hitherto collected concerning the application of HNTs towards cancer therapy. Despite their reproducibility issues, HNTs were used as nanoarchitectonic platforms for the delivery of conventional chemotherapeutic, natural-occurring, biopharmaceutical, and phototherapeutic anticancer agents in a wide range of in vitro and in vivo solid cancer models. Overall, in different types of cancer mice models, the intratumoral and intravenous administration of HNTs-based nanoplatforms induced tumor growth inhibition without causing significant toxic effects. Such evidence raises a relevant question: does the therapeutic benefit of the parenteral administration of HNTs in cancer outweigh their potential toxicological risk? To answer this question further long-term absorption-distribution-metabolism-excretion studies in healthy and cancer animal models need to be performed. In cancer therapeutics, HNTs are envisaged as promising platforms for cancer multi-agent therapy, enabling the combination of different therapeutic modalities. Furthermore, HNTs might constitute suitable nanotheranostic platforms. Nevertheless, to confirm the potential and safety of the application of HNTs as nanodelivery systems for cancer therapy, it is necessary to perform in-depth in vivo pharmacokinetics and pharmacodynamic studies to further the translation to clinical trials.