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.

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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.

Modern Alchemy: Natural clay-derived nanosheets for cancer therapy
Modern Alchemy: Natural Clay-Derived Nanosheets for Photo-Induced Cancer Therapy

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.

Nature-Derived 2-Dimensional Materials
Nature-Derived 2-Dimensional Materials Fabrication and PEGylation

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.

Nature-Derived 2-Dimensional Materials for Cancer Therapy
Nature-Derived 2-Dimensional Materials for Cancer Therapy

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.

Nature-Derived 2-Dimensional Materials with synergistic photo-enhanced PDT/CDT/PTT
Nature-Derived 2-Dimensional Materials with Synergistic Photo-Enhanced PDT/CDT/PTT

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.

A tunable electron band structure and a conductive band with excellent light response characteristics for energy, photocatalysis, and biomedical engineering
Nature-Derived 2-Dimensional Materials Display a Tunable Electron Band Structure and a Conductive Band with Excellent Light Response Characteristics for Energy, Photocatalysis, and Biomedical Engineering Applications.

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. 

Related reading:https://orcid.org/0000-0001-7114-1095  https://www.nature.com/articles/s41467-021-21436-5  https://www.nature.com/articles/s41578-020-00247-y  https://doi.org/10.1038/s41467-019-12462-5 https://bioengineeringcommunity.nature.com/posts/tackling-covid-19-with-materials-science  https://bioengineeringcommunity.nature.com/posts/micropatterned-microfluidics-dendronized-fluorosurfactants-for-highly-stable-emulsions

Related Cancer Theranostics works:

  1. D Gao, T Chen, Y Han, S Chen, Y Wang, X Guo, H Wang, X Chen, M Guo, Y Zhang, G Hong, X Zhang*, Z Tian*, Z Yang*. Targeting Hypoxic Tumors with Hybrid Nanobullets for Oxygen-independent Synergistic Photothermal-thermodynamic Therapy. Nano-Micro Letters, 2021,13, 99. (Featured Cover Paper)
  2. X Ji, L Ge, C Liu, Z Tang, Y Xiao, Z Lei, W Gao, S Blake, D De, X Zeng, Na Kong,* X Zhang*, W Tao*. Capturing functional two-dimensional nanosheets from sandwich-structure vermiculite: synthesis and application in cancer theranostics. Nature Communications, 2021,12,1124.
  3. Y Wang, D Gao, Y Liu, X Guo, S Chen, L Zeng, J Ma, X Zhang*, Z Tian*, Z Yang*. Immunogenic-Cell-Killing and Immunosuppression-Inhibiting Nanomedicine. Bioactive Materials, 2020, 6 (6), 1513-1527.
  4. J Yang†, X Zhang†, C Liu†, Z Wang, L Deng, C Feng, W Tao, X Xua, W Cui. Biologically Modified Nanoparticles as Theranostic Progress in Materials Science, 2021, 118, 100768.
  5. Z Yang, D Gao, X Guo, L Jin, J Zhang, Y Wang, S Chen, X Zheng, L Zeng, M Guo, X Zhang*, Z Tian*. Fighting immune cold and reprogramming immunosuppressive tumor microenvironment with red blood cell membrane-camouflaged ACS Nano, 2020, 14, 12, 17442-17457.
  6. D Wei, Y Yu, Y Huang,1 Y Jiang, Y Zhao, Z Nie, F Wang, W Ma, Z Yu, Y Huang, X Zhang, Z Liu, X Zhang, H Xiao. A Near-Infrared-II Polymer with Tandem Fluophores Demonstrates Superior Biodegradability for Simultaneous Drug Tracking and Treatment Efficacy Feedback. ACS Nano, 2021, 15 (3), 5428–5438.
  7. D Wei, Y Yu, X Zhang, Y Wang, H Chen, Y Zhao, F Wang, G Rong, W Wang, X Kang, J Cai, Z Wang, J Yin, M Hanif, Y Sun, G Zha, L Li, G Nie, H Xiao*. Breaking down the intracellular redox balance with diselenium nanoparticles for maximizing chemotherapy efficacy on patient-derived xenograft models. ACS Nano, 2020, 14, 12, 16984-16996.
  8. Z Lei, W Zhu, X Zhang, X Wang, P Wu. Bio-inspired ionic skin for theranostics hydrogel. Advanced Functional Materials, 2020, 2008020.
  9. D Gao, X Guo, X Zhang*, S Chen, Y Wang, T Chen, G Huang, Y Gao, Z Tian*, Z Yang*. Multifunctional phototheranostic nanomedicine for cancer imaging and Materials Today Bio. 2019, 5,100035. (Invited Paper, ESI highly cited paper, open access with a fee waiver, 99.983% excellence, 2nd most highly cited paper of Materials Today Bio)
  10. J Ouyang†, X Ji†, X Zhang†, C Feng, Z Tang, N Kong, A Xie, J Wang, X Sui, L Deng, Y Liu, J S Kim, Y Cao, W Tao*. In situ sprayed NIR-responsive, analgesic black phosphorus-based gel for diabetic ulcer Proceedings of the National Academy of Sciences of the United States of America (PNAS), 2020, 117 (46), 28667-28677. (highly cited paper, Highlighted by: MRS Bulletin Materials News)
  11. G Parekh, Y Shi, J Zheng, X Zhang*, S Leporatti. Nano-carriers for targeted delivery and biomedical imaging enhancement. Therapeutic Delivery, 2018, 9(6), 451-468.
  12.  C Liu, S Sun, Q Feng, Y Wu, N Kong, Z Yu, J Yao, X Zhang, W Chen, Z Tang,  Y Xiao, X Huang, A Lv, Y Cao, A Wu, T Xie, W Tao. Arsenene nanodot: a new-concept arsenical drug with selective killing effects for solid tumor therapy. Advanced Materials. doi:10.1002/adma.202102054. 

Related Nature-derived/inspired materials/tea works:

  1. Y Xie, J Yin, J Zheng, L Wang, J Wu, M Dresselhaus, X Zhang*. Synergistic cobalt sulfide/eggshell membrane carbon ACS Applied Materials & Interfaces. 2019, 11 (35), 32244-32250.
  2. Z Li, D Chu, Y Gao, L Jin*, X Zhang*, W Cui, J Li*. Biomimicry, biomineralization, and bioregeneration of bone using advanced three-dimensional fibrous hydroxyapatite Materials Today Advances. 2019,3,100014. (Invited open-access paper among most highly cited paper of Materials Today Advances)
  3. Z Lei, W Zhu, X Zhang, X Wang, P Wu. Bio-inspired ionic skin for theranostics hydrogel. Advanced Functional Materials, 2020, 2008020.
  4. L Jin, J Li, L Liu*, Z Wang*, X Zhang*. Facile synthesis of carbon dots with superior sensing. Applied Nanoscience, 2018, 755(3), 1-8.
  5. X Ji, L Ge, C Liu, Z Tang, Y Xiao, Z Lei, W Gao, S Blake, D De, X Zeng, Na Kong*, X Zhang*, W Tao*. Capturing functional two-dimensional nanosheets from sandwich-structure vermiculite: synthesis and application in cancer theranostics. Nature Communications, 2021,12,1124.
  6. J Yang†, X Zhang†, C Liu†, Z Wang, L Deng, C Feng, W Tao, X Xua, W Cui. Biologically Modified Nanoparticles as Theranostic Progress in Materials Science, 2021, 118, 100768.
  7. Z Yang, D Gao, X Guo, L Jin, J Zhang, Y Wang, S Chen, X Zheng, L Zeng, M Guo, X Zhang*, Z Tian*. Fighting immune cold and reprogramming immunosuppressive tumor microenvironment with red blood cell membrane-camouflaged ACS Nano, 2020, 14, 12, 17442-17457.
  8. Y Wang, L Lu, G Zheng*, X Zhang*. Microenvironment-controlled micropatterned microfluidic model for biomimetic in-situ ACS Nano, 2020, 14(8), 9861-9872. (Featured Cover Paper)
  9. P Tang, D Shen, Y Xu, X Zhang*, J Shi, J Yin*. Effect of fermentation conditions and the tenderness of tea leaves on the chemical components and sensory quality of fermented juice. Journal of Chemistry, 2018, 4312875,1-7.
  10. X Chen, Y Chen, L Zou, X Zhang, Y Dong, J Tang, D McClements, W Liu. Plant-based Nanoparticles Consisting of a Protein Core and Multilayer Phospholipid Shell: Fabrication, Stability, and  Journal of Agricultural and Food Chemistry, 2019, 67 (23), 6574-6584.
  11. X Zhang*. Tea and cancer prevention. Journal of Cancer Research Updates, 2015, 4 (2), 65-73.
  12. Q Zhang, W Li, K Li, H Nan, C Shi, Y Zhang, Z Dai, Y Lin, X Yang, Y Tong, D Zhang, C Lu, L Feng, C Wang, X Liu, J Huang, W Jiang, X Wang, X Zhang, Eichler, Z. Liu, L. Gao. The Chromosome-Level Reference Genome of Tea Tree Unveils Recent Bursts of Non-autonomous LTR Retrotransposons in Driving Genome Size Evolution. Molecular plant 2020,13 (7), 935-938.
  13. Y Yang†, P Jin†, X Zhang†, N Ravichandran, H Ying, C Yu, H Ying, Y Xu, J Yin, K Wang, M Wu, Q New epigallocatechin gallate (EGCG) nanocomplexes co-assembled with 3-mercapto-1-hexanol and ß- lactoglobulin for improvement of antitumor activity. Journal of Biomedical Nanotechnology, 2017,13 (7), 805-814.
  14. X Zhang*, G Parekh, B Guo, X Huang, Y Dong, W Han, X Chen, G Polyphenol and Self-Assembly: Metal Polyphenol Nanonetwork for Drug Delivery and Biomedical Applications. Future Drug Discovery, 2019, 1 (1), FDD7. (Invited open-access paper with a fee waiver, most cited paper of the journal)

Related 2-dimentional/carbon materials works:

  1. L Jin, X Guo, D Gao, G Tan, N Du, X Wang, Y Zhang, Z Yang*, X Zhang*. NIR-responsive MXene nanobelts for wound NPG Asia Materials. 2021,13, 24. Selected for the “Special Issue on Biomaterials and Health-care related Materials”.
  2. J Meng, J Li, J Liu, X Zhang*, G Jiang*, L Ma, Z Hu, S Xi, Y Zhao, M Yan, P Wang, X Liu, Q Li, J Liu, T Wu, L Mai*. Universal Approach to Fabricating Graphene-Supported Single-Atom Catalysts from  Doped ZnO  Solid ACS Central Science, 2020, 6(8), 1431–1440.
  3. J Cui, J Yin, J Zheng, J Meng, M Liao, T Wu, S He, S Wei, Z Xie, H Wang, M Dresselhaus, Y Xie*, J Wu*,  C Lu*, X Zhang*. Supermolecule cucurbituril subnanoporous carbon supercapacitor(SCSCS). Nano Letters, 2021, 21 (5), 2156–2164.
  4. J Meng, Z Liu, X Liu, W Yang, L Wang, Y Li, Y Cao, X Zhang*, L Mai*. Scalable fabrication and active site identification of MOF shell-derived nitrogen-doped carbon hollow frameworks for oxygen Journal of Materials Science & Technology, 2020, 66, 186-192.
  5. F Han, S Lv, Z Li, L Jin, B Fan*, J Zhang, R Zhang, X Zhang*, L Han, J Li*. Triple-synergistic 2D material- based dual-delivery antibiosis platform. NPG Asia Materials, 2020,12,15.
  6. J Ouyang†, X Ji†, X Zhang†, C Feng, Z Tang, N Kong, A Xie, J Wang, X Sui, L Deng, Y Liu, J S Kim, Y Cao, W Tao*. In situ sprayed NIR-responsive, analgesic black phosphorus-based gel for diabetic ulcer Proceedings of the National Academy of Sciences of the United States of America (PNAS), 2020, 117 (46), 28667-28677. (highly cited paper, Highlighted by: MRS Bulletin Materials News)
  7. H Zhou*, Z Wang, W Zhao, X Tong, X Jin, X Zhang*, Y Yu, H Liu, Y Ma, S Li, W Robust and sensitive pressure/strain sensors from solution processable composite hydrogels enhanced by hollow-structured conducting polymers. Chemical Engineering Journal, 2020, 403, 126307.
  8. X Ji, L Ge, C Liu, Z Tang, Y Xiao, Z Lei, W Gao, S Blake, D De, X Zeng, Na Kong*, X Zhang*, W Tao*. Capturing functional two-dimensional nanosheets from sandwich-structure vermiculite: synthesis and application in cancer theranostics. Nature Communications, 2021,12,1124.
  9. J Meng, Q He, L Xu, X Zhang, F Liu, X Wang, Q Li, X Xu, G Zhang, C Niu, Z Identification of phase control of carbon-confined Nb2O5 nanoparticles towards high-performance lithium  storage.  Advanced Energy Materials, 2019, 9 (18), 1802695.
  10. J Wu, F Xu, S Li, Q, Liu, X Zhang, Q Liu, R Fu, D Wu. Porous polymers as multifunctional material platforms toward task‐specific applications. Advanced  Materials,  2019,  31(4),  1802922.  (Citation>145,  ESI Highly Cited Paper, Invited Paper)
  11. B Zheng, X Lin, X Zhang, D Wu, K Matyjaszewski. Emerging functional porous polymeric and carbonaceous materials for environment treatment and energy storage. Advanced Functional  Materials, 2019, 1907006. (Invited Paper)
  12. R Huang, X Chen, Y Dong, X Zhang*, Y Wei, Z Yang, W Li, Y Guo, J Liu, Z Yang*, H Wang*, L Jin*.

    MXene composite nanofibers for cell culture and tissue engineering. ACS Applied Bio Materials. 2020, 3(4), 2125-2131.

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

Contact: Dr. Xingcai Zhang xingcai@mit.edu  chemmike1984@gmail.com +1-2253041387 wechat:drtea1

Xingcai Zhang

Harvard/MIT Research Fellow, Harvard University

Sustainable Nature-inspired/dervied/mimetic materials, nanomaterials, biomedicine, lab-on-chip, 2D/C/porous/polymer materials, tea. 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 https://orcid.org/0000-0001-7114-1095 Contact: xingcai@mit.edu +1-2253041387 wechat:drtea1