Nature-Derived 2-Dimensional Materials for Cancer Therapy and Sustainable Solutions
Nature-derived/inspired materials shine the glory of Nature for diverse sustainable energy, environment, catalysis, and especially biomedical applications due to their unique advantages.
Mother Nature provides us with abundant materials, ideas, possibilities, and sustainable solutions. Nature-derived/inspired materials shine the glory of Nature for diverse sustainable energy, environment, and especially biomedical applications due to their unique advantages including but not limited to the excellent biocompatibility, biodegradability, vast abundance, low-cost, and diverse functionalities.
Can you imagine using clays as natural materials to make nanorobots for cancer therapy? Scientists from Harvard University etc. made 2-dimensional (2D) nanosheets materials with FDA-approved compositions from clays for diverse applications including cancer therapy. Clays, also referred to as phyllosilicate minerals, are fundamentally composed of tetrahedral silicon (SiO2) and/or aluminum oxide (Al2O3) crystal structures. In the recent Nature Communication (2021, 12, 1124 https://doi.org/10.1038/s41467-021-21436-5) paper, a universal exfoliation method that can intelligently “capture” the ultrathin, biocompatible, and functional core layers (FCLs: MgO and Fe2O3, both are FDA-approved) sandwiched between two identical tetrahedral layers (SiO2 and Al2O3) from 2:1 aluminosilicate (vermiculite (VMT), biotite, flogopite, illite, etc.) is developed by a combination of ball-grinding, calcination, etching, and sonication. The as-prepared NSs have an average thickness and size of 2.7 nm and 110 nm, respectively. For nanomedicines used in vivo, physiological stability and dispersibility are important indicators that the FCL NSs (nanosheets) were further modified by positively charged PEG-NH2, with the average thickness of FCL-PEG NSs increased to 6 nm, demonstrating successful PEG-NH2 functionalization. The average size of FCL-PEG NSs decreased to 105 nm, due to the use of bath sonication to break down FCL NSs during PEGylation. Considering the FDA-approved MgO and Fe2O3 are widely used in the clinic for the treatment of stomach diseases and iron deficiency, respectively, the innovative grown layers are biocompatible and potentially highly impactful in terms of basic science and translational medicine. Moreover, a series of toxicity studies (both in vivo and in vitro) were performed to further support and highlight the good biocompatibility of the obtained FCL-PEG NSs in the study. This study further specifically pioneers their application in cancer theranostics as an example and also shows their potential as a prelude to the future extensive studies of 2D NSs.
The FCL-PEG NSs had a strong ability to modulate tumor microenvironment (TME) through catalyzing H2O2 to produce O2 and consuming GSH due to the existence Fe3+ in FCL-PEG NSs, which could relieve hypoxia and diminish the antioxidant capability of the tumor.
Fe3+ + GSH → Fe2+ + GSSG (1)
Fe3+ + H2O2 → Fe2+ + H2O + O2↑ (2)
The as-prepared NSs possess a tunable and appropriate electron band structure with the bandgap decreased from 2.0 eV to 1.4 eV and the conductive band increased from -0.4 eV to -0.6 eV, endowing them a huge potential in energy, catalysis, and biomedicine. Benefiting from the narrowed band gap and improved ΔE between the conductive band of FCL-PEG NSs and E0 of O2/·O2−, effective electron-hole separation of FCL NSs was obtained upon 658 nm laser irradiation, which facilitated the ·O2− generation from O2 and exhibited a high photodynamic therapy (PDT) efficacy. Moreover, the capacity of nanosheets for the generation of ·OH in the TME via the Fe2O3-catalyzed Fenton reaction could be significantly enhanced by 808 nm and 658 nm laser exposures, which further endowed the functional nanosheets with potential for photo-enhanced chemodynamic therapy (CDT). Meanwhile, for photothermal therapy (PTT), the FCL-PEG NSs exhibited high photothermal conversion efficiency when exposed to 808 nm laser irradiation, which leads to prominent synergistic and photo-enhanced PDT/CDT/PTT. FCL-PEG NSs also showed great utility in photoacoustic (PA), photothermal, and fluorescent imaging.
Good stability of FCL-PEG NSs in the physical environment (e.g., in PBS or saline) is a great advantage for the production, storage, and transportation of NSs-based therapeutics for medical use in the future. Besides their high storage stability, TME-triggered biodegradation of FCL-PEG NSs was also observed. Considering that (i) injected FCL-PEG NSs in major organs can be excreted from the body gradually and those in tumors can be degraded (i.e., biocompatibility), (ii) the main ingredients of FCL-PEG NSs are FDA-approved (i.e., biocompatibility and clinical potential), and (iii) the excellent storage stability of the FCL-PEG NSs (i.e., an advantage in the production, storage, and transportation), the developed FCL-PEG NSs may possess great potential in biomedical applications.
It is worth mentioning that, the FCL-based NSs developed in this study also present a good example exhibiting the evolution from a commonly used traditional Chinese medicine (i.e., the raw material VMT, which is included in the Chinese pharmacopeia) to a new photonic nanomedicine, which is enabled by nanotechnology and materials science-based technology. Future studies in the development of traditional Chinese medicine may be greatly inspired by such kind of perspective from the emerging nanotechnology and materials science fields.
To sum up, this work not only provides a smart strategy to intelligently “capture” the sandwiched FCLs from clay materials but also demonstrated proof-of-concept application of the obtained 2D NSs in cancer theranostics. The raw materials are cheap and widely sourced in Nature, and the efficient preparation method has high universality, which is appropriate for all-natural and synthetic 2:1 aluminosilicates. Moreover, the NSs alone integrate the regulation of TME, PTT/PDT/CDT, and multi-mode imaging, serving as an efficient and comprehensive nanomedicine for cancer theranostics. More interestingly, this work is expected to supply a brand-new strategy for the preparation of 2D bioactive nanomaterials from Natural materials with tunable electron band structure and expand their in-depth applications in sustainable energy, environment, photocatalysis, and especially biomedical engineering fields.
Dr. Xingcai Zhang, Harvard/MIT Research Fellow; Science Writer/Editorial (Advisory) Board Member for Springer Nature, Elsevier, Materials Today, Royal Society of Chemistry, Wiley; Nature Nano Ambassador with 5 STEM degrees/strong background in sustainable Nature-derived/inspired/mimetic materials for biomed/sensing/catalysis/energy/environment applications, with around 100 high-impact journal publications in Nature Reviews Materials (featured cover paper), etc. https://scholar.google.com/citations?hl=en&user=2vDraMoAAAAJ&view_op=list_works&sortby=pubdate