Abstract
Two dimensional (2D) materials have attracted extravagant eminence in the area of biomedical applications due to their distinctive structure, biocompatibility, and physicochemical properties. Mono-layered black phosphorus (BP), also known as phosphorene, is a thermodynamically stable allotrope of phosphorous and is the very recent member of the 2D family has lured tremendous scientific interest since its rediscovery in 2014. The exceptional properties of BP including high carrier mobility, large specific surface area, tunable band gap, intrinsic anisotropy, and inherent in vivo biocompatibility and biodegradability make it an ideal alternative to other 2D materials in biomedical applications. This chapter summarizes various biomedical applications of BP including drug delivery, bio-imaging, bio-sensing, photothermal/photodynamic therapy, and theranostics. The main focus of this chapter is to emphasize the efficacy of BP nanosheets (NSs) and quantum dots (QDs) as robust and tunable diagnostic and therapeutic platforms. Finally, the current challenges and future perspectives in biomedical applications of BP have also been addressed.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
de Menezes, B.R.C., Rodrigues, K.F., da Silva Fonseca, B.C., et al.: Recent advances in the use of carbon nanotubes as smart biomaterials. J. Mater. Chem. B 7, 1343–1360 (2019). https://doi.org/10.1039/C8TB02419G
Patz, J.A., Graczyk, T.K., Geller, N., Vittor, A.Y.: Effects of environmental change on emerging parasitic diseases. Int. J. Parasitol. 30, 1395–1405 (2000). https://doi.org/10.1016/S0020-7519(00)00141-7
Kumar, S., Rani, R., Dilbaghi, N., et al.: Carbon nanotubes: a novel material for multifaceted applications in human healthcare. Chem. Soc. Rev. 46, 158–196 (2017). https://doi.org/10.1039/C6CS00517A
Partha, R., Conyers, J.L.: Biomedical applications of functionalized fullerene-based nanomaterials. Int. J. Nanomed. 4, 261–275 (2009)
Gao, J., Wang, H.L., Shreve, A., Iyer, R.: Fullerene derivatives induce premature senescence: a new toxicity paradigm or novel biomedical applications. Toxicol. Appl. Pharmacol. 244, 130–143 (2010). https://doi.org/10.1016/J.TAAP.2009.12.025
Erol, O., Uyan, I., Hatip, M., et al.: Recent advances in bioactive 1D and 2D carbon nanomaterials for biomedical applications. Nanomed. Nanotechnol. Biol. Med. 14, 2433–2454 (2018). https://doi.org/10.1016/J.NANO.2017.03.021
Bianco, A., Kostarelos, K., Partidos, C.D., Prato, M.: Biomedical applications of functionalised carbon nanotubes. Chem. Commun. 0, 571 (2005). https://doi.org/10.1039/b410943k
Klingeler, R., Sim, R.B.: Carbon Nanotubes for Biomedical Applications. Springer, Berlin, Heidelberg (2011)
Shen, H., Zhang, L., Liu, M., Zhang, Z.: Biomedical applications of graphene. Theranostics 2, 283–294 (2012). https://doi.org/10.7150/thno.3642
Yang, Y., Asiri, A.M., Tang, Z., et al.: Graphene based materials for biomedical applications. Mater. Today 16, 365–373 (2013). https://doi.org/10.1016/J.MATTOD.2013.09.004
Zhang, Y., Nayak, T.R., Hong, H., Cai, W.: Graphene: a versatile nanoplatform for biomedical applications. Nanoscale 4, 3833 (2012). https://doi.org/10.1039/c2nr31040f
Chimene, D., Alge, D.L., Gaharwar, A.K.: Two-dimensional nanomaterials for biomedical applications: emerging trends and future prospects. Adv. Mater. 27, 7261–7284 (2015). https://doi.org/10.1002/adma.201502422
Luo, M., Fan, T., Zhou, Y., et al.: 2D black phosphorus-based biomedical applications. Adv. Funct. Mater. 29, 1808306 (2019). https://doi.org/10.1002/adfm.201808306
Li, L., Yu, Y., Ye, G.J., et al.: Black phosphorus field-effect transistors. Nat. Nanotechnol. 9, 372–377 (2014). https://doi.org/10.1038/nnano.2014.35
Liu, H., Neal, A.T., Zhu, Z., et al.: Phosphorene: an unexplored 2D semiconductor with a high hole mobility. ACS Nano 8, 4033–4041 (2014). https://doi.org/10.1021/nn501226z
Castellanos-Gomez, A., Vicarelli, L., Prada, E., et al.: Isolation and characterization of few-layer black phosphorus. 2D Mater. 1, 025001 (2014). https://doi.org/10.1088/2053-1583/1/2/025001
Wang, X., Jones, A.M., Seyler, K.L., et al.: Highly anisotropic and robust excitons in monolayer black phosphorus. Nat. Nanotechnol. 10, 517–521 (2015). https://doi.org/10.1038/nnano.2015.71
Wang, Y.W., Liu, S., Zeng, B.W., et al.: Ultraviolet saturable absorption and ultrafast carrier dynamics in ultrasmall black phosphorus quantum dots. Nanoscale 9, 4683–4690 (2017). https://doi.org/10.1039/C6NR09235G
Wu, J., Koon, G.K.W., Xiang, D., et al.: Colossal ultraviolet photoresponsivity of few-layer black phosphorus. ACS Nano 9, 8070–8077 (2015). https://doi.org/10.1021/acsnano.5b01922
Zhu, M., Osakada, Y., Kim, S., et al.: Black phosphorus: a promising two dimensional visible and near-infrared-activated photocatalyst for hydrogen evolution. Appl. Catal. B Environ. 217, 285–292 (2017). https://doi.org/10.1016/J.APCATB.2017.06.002
Qiu, M., Wang, D., Liang, W., et al.: Novel concept of the smart NIR-light–controlled drug release of black phosphorus nanostructure for cancer therapy. Proc. Natl. Acad. Sci. 115, 501–506 (2018). https://doi.org/10.1073/PNAS.1714421115
Shao, J., Xie, H., Huang, H., et al.: Biodegradable black phosphorus-based nanospheres for in vivo photothermal cancer therapy. Nat. Commun. 7, 12967 (2016). https://doi.org/10.1038/ncomms12967
Fojtů, M., Chia, X., Sofer, Z., et al.: Black phosphorus nanoparticles potentiate the anticancer effect of oxaliplatin in ovarian cancer cell line. Adv. Funct. Mater. 27, 1701955 (2017). https://doi.org/10.1002/adfm.201701955
Lee, H.U., Park, S.Y., Lee, S.C., et al.: Black phosphorus (BP) nanodots for potential biomedical applications. Small 12, 214–219 (2016). https://doi.org/10.1002/smll.201502756
Wei, Q., Peng, X.: Superior mechanical flexibility of phosphorene and few-layer black phosphorus. Appl. Phys. Lett. 104, 251915 (2014). https://doi.org/10.1063/1.4885215
Jiang, J.-W., Park, H.S.: Mechanical properties of single-layer black phosphorus. J. Phys. D Appl. Phys. 47, 385304 (2014). https://doi.org/10.1088/0022-3727/47/38/385304
Li, X., Deng, B., Wang, X., et al.: Synthesis of thin-film black phosphorus on a flexible substrate. 2D Mater. 2, 031002 (2015). https://doi.org/10.1088/2053-1583/2/3/031002
Chen, Y., Ren, R., Pu, H., et al.: Field-effect transistor biosensors with two-dimensional black phosphorus nanosheets. Biosens. Bioelectron. 89, 505–510 (2017). https://doi.org/10.1016/J.BIOS.2016.03.059
Zhang, X., Zhang, Z., Zhang, S., et al.: Size effect on the cytotoxicity of layered black phosphorus and underlying mechanisms. Small 13, 1701210 (2017). https://doi.org/10.1002/smll.201701210
Latiff, N.M., Teo, W.Z., Sofer, Z., et al.: The cytotoxicity of layered black phosphorus. Chem. A Eur. J. 21, 13991–13995 (2015). https://doi.org/10.1002/chem.201502006
Lin, J., Wang, S., Huang, P., et al.: Photosensitizer-loaded gold vesicles with strong plasmonic coupling effect for imaging-guided photothermal/photodynamic therapy. ACS Nano 7, 5320–5329 (2013). https://doi.org/10.1021/nn4011686
Thangavel, S., Yoshitomi, T., Sakharkar, M.K., Nagasaki, Y.: Redox nanoparticle increases the chemotherapeutic efficiency of pioglitazone and suppresses its toxic side effects. Biomaterials 99, 109–123 (2016). https://doi.org/10.1016/J.BIOMATERIALS.2016.05.001
Sun, Z., Xie, H., Tang, S., et al.: Ultrasmall black phosphorus quantum dots: synthesis and use as photothermal agents. Angew. Chemie. Int. Ed. 54, 11526–11530 (2015). https://doi.org/10.1002/anie.201506154
Sun, C., Wen, L., Zeng, J., et al.: One-pot solventless preparation of PEGylated black phosphorus nanoparticles for photoacoustic imaging and photothermal therapy of cancer. Biomaterials 91, 81–89 (2016). https://doi.org/10.1016/J.BIOMATERIALS.2016.03.022
Zhao, Y., Tong, L., Li, Z., et al.: Stable and multifunctional dye-modified black phosphorus nanosheets for near-infrared imaging-guided photothermal therapy. Chem. Mater. 29, 7131–7139 (2017). https://doi.org/10.1021/acs.chemmater.7b01106
Xing, C., Chen, S., Qiu, M., et al.: Conceptually novel black phosphorus/cellulose hydrogels as promising photothermal agents for effective cancer therapy. Adv. Healthc. Mater. 7, 1701510 (2018). https://doi.org/10.1002/adhm.201701510
Shao, J., Ruan, C., Xie, H., et al.: Black-phosphorus-incorporated hydrogel as a sprayable and biodegradable photothermal platform for postsurgical treatment of cancer. Adv. Sci. 5, 1700848 (2018). https://doi.org/10.1002/advs.201700848
Wang, H., Yang, X., Shao, W., et al.: Ultrathin black phosphorus nanosheets for efficient singlet oxygen generation. J. Am. Chem. Soc. 137, 11376–11382 (2015). https://doi.org/10.1021/jacs.5b06025
Guo, T., Wu, Y., Lin, Y., et al.: Black phosphorus quantum dots with renal clearance property for efficient photodynamic therapy. Small 14, 1702815 (2018). https://doi.org/10.1002/smll.201702815
Song, G., Chen, M., Zhang, Y., et al.: Janus iron oxides @ semiconducting polymer nanoparticle tracer for cell tracking by magnetic particle imaging. Nano Lett. 18, 182–189 (2018). https://doi.org/10.1021/acs.nanolett.7b03829
Ju, Y., Zhang, H., Yu, J., et al.: Monodisperse Au–Fe2C Janus nanoparticles: an attractive multifunctional material for triple-modal imaging-guided tumor photothermal therapy. ACS Nano 11, 9239–9248 (2017). https://doi.org/10.1021/acsnano.7b04461
Song, J., Wu, B., Zhou, Z., et al.: Double-layered plasmonic-magnetic vesicles by self-assembly of Janus amphiphilic gold-iron(II, III) oxide nanoparticles. Angew. Chemie. Int. Ed. 56, 8110–8114 (2017). https://doi.org/10.1002/anie.201702572
Zhang, D., Lin, Z., Lan, S., et al.: The design of Janus black phosphorus quantum dots@metal–organic nanoparticles for simultaneously enhancing environmental stability and photodynamic therapy efficiency. Mater. Chem. Front. 3, 656–663 (2019). https://doi.org/10.1039/C8QM00623G
Dong, Z., Gong, H., Gao, M., et al.: polydopamine nanoparticles as a versatile molecular loading platform to enable imaging-guided cancer combination therapy. Theranostics 6, 1031–1042 (2016). https://doi.org/10.7150/thno.14431
Sun, X., Wang, C., Gao, M., et al.: Remotely controlled red blood cell carriers for cancer targeting and near-infrared light-triggered drug release in combined photothermal-chemotherapy. Adv. Funct. Mater. 25, 2386–2394 (2015). https://doi.org/10.1002/adfm.201500061
Ogretmen, B., Safa, A.R.: Expression of the mutated p53 tumor suppressor protein and its molecular and biochemical characterization in multidrug resistant MCF-7/Adr human breast cancer cells. Oncogene 14, 499–506 (1997). https://doi.org/10.1038/sj.onc.1200855
Wu, F., Zhang, M., Chu, X., et al.: Black phosphorus nanosheets-based nanocarriers for enhancing chemotherapy drug sensitiveness via depleting mutant p53 and resistant cancer multimodal therapy. Chem. Eng. J. 370, 387–399 (2019). https://doi.org/10.1016/J.CEJ.2019.03.228
Zong, S., Wang, L., Yang, Z., et al.: Black phosphorus-based drug nanocarrier for targeted and synergetic chemophotothermal therapy of acute lymphoblastic leukemia. ACS Appl. Mater. Interfaces 11, 5896–5902 (2019). https://doi.org/10.1021/acsami.8b22563
Yin, F., Hu, K., Chen, S., et al.: Black phosphorus quantum dot based novel siRNA delivery systems in human pluripotent teratoma PA-1 cells. J. Mater. Chem. B 5, 5433–5440 (2017). https://doi.org/10.1039/C7TB01068K
Baumann, B., Jungst, T., Stichler, S., et al.: Control of nanoparticle release kinetics from 3D printed hydrogel scaffolds. Angew. Chemie. Int. Ed. 56, 4623–4628 (2017). https://doi.org/10.1002/anie.201700153
Khademhosseini, A., Langer, R.: A decade of progress in tissue engineering. Nat. Protoc. 11, 1775–1781 (2016). https://doi.org/10.1038/nprot.2016.123
Zhang, Y., Zhai, D., Xu, M., et al.: 3D-printed bioceramic scaffolds with antibacterial and osteogenic activity. Biofabrication 9, 025037 (2017). https://doi.org/10.1088/1758-5090/aa6ed6
Shi, W., Sun, M., Hu, X., et al.: Structurally and functionally optimized silk-fibroin-gelatin scaffold using 3D printing to repair cartilage injury in vitro and in vivo. Adv. Mater. 29, 1701089 (2017). https://doi.org/10.1002/adma.201701089
Yang, B., Yin, J., Chen, Y., et al.: 2D-black-phosphorus-reinforced 3D-printed scaffolds: a stepwise countermeasure for osteosarcoma. Adv. Mater. 30, 1705611 (2018). https://doi.org/10.1002/adma.201705611
Xu, M., Wang, L.V.: Photoacoustic imaging in biomedicine. Rev. Sci. Instrum. 77, 041101 (2006). https://doi.org/10.1063/1.2195024
Li, C., Wang, L.V.: Photoacoustic tomography and sensing in biomedicine. Phys. Med. Biol. 54, R59–R97 (2009). https://doi.org/10.1088/0031-9155/54/19/R01
Wang, L.V.: Multiscale photoacoustic microscopy and computed tomography. Nat. Photon. 3, 503–509 (2009). https://doi.org/10.1038/nphoton.2009.157
Sun, Z., Zhao, Y., Li, Z., et al.: TiL4—coordinated black phosphorus quantum dots as an efficient contrast agent for in vivo photoacoustic imaging of cancer. Small 13, 1602896 (2017). https://doi.org/10.1002/smll.201602896
Carr, J.A., Franke, D., Caram, J.R., et al.: Shortwave infrared fluorescence imaging with the clinically approved near-infrared dye indocyanine green. Proc. Natl. Acad. Sci. 115, 4465–4470 (2018). https://doi.org/10.1073/PNAS.1718917115
Zhang, M., Wang, W., Cui, Y., et al.: Near-infrared light-mediated photodynamic/photothermal therapy nanoplatform by the assembly of Fe3O4 carbon dots with graphitic black phosphorus quantum dots. Int. J. Nanomed. 13, 2803–2819 (2018). https://doi.org/10.2147/IJN.S156434
Liu, T., Wang, C., Cui, W., et al.: Combined photothermal and photodynamic therapy delivered by PEGylated MoS2 nanosheets. Nanoscale 6, 11219–11225 (2014). https://doi.org/10.1039/C4NR03753G
Yang, X., Wang, D., Shi, Y., et al.: Black phosphorus nanosheets immobilizing Ce6 for imaging-guided photothermal/photodynamic cancer therapy. ACS Appl. Mater. Interfaces 10, 12431–12440 (2018). https://doi.org/10.1021/acsami.8b00276
Lane, L.A., Qian, X., Nie, S.: SERS nanoparticles in medicine: from label-free detection to spectroscopic tagging. Chem. Rev. 115, 10489–10529 (2015). https://doi.org/10.1021/acs.chemrev.5b00265
Liu, Z., Chen, H., Jia, Y., et al.: A two-dimensional fingerprint nanoprobe based on black phosphorus for bio-SERS analysis and chemo-photothermal therapy. Nanoscale 10, 18795–18804 (2018). https://doi.org/10.1039/C8NR05300F
Zhao, Y., Zhang, Y.-H., Zhuge, Z., et al.: Synthesis of a poly-l-lysine/black phosphorus hybrid for biosensors. Anal. Chem. 90, 3149–3155 (2018). https://doi.org/10.1021/acs.analchem.7b04395
Kumar, V., Brent, J.R., Shorie, M., et al.: Nanostructured aptamer-functionalized black phosphorus sensing platform for label-free detection of myoglobin, a cardiovascular disease biomarker. ACS Appl. Mater. Interfaces 8, 22860–22868 (2016). https://doi.org/10.1021/acsami.6b06488
Yew, Y.T., Sofer, Z., Mayorga-Martinez, C.C., Pumera, M.: Black phosphorus nanoparticles as a novel fluorescent sensing platform for nucleic acid detection. Mater. Chem. Front. 1, 1130–1136 (2017). https://doi.org/10.1039/C6QM00341A
Qiu, M., Singh, A., Wang, D., et al.: Biocompatible and biodegradable inorganic nanostructures for nanomedicine: silicon and black phosphorus. Nano Today 25, 135–155 (2019). https://doi.org/10.1016/J.NANTOD.2019.02.012
Li, Z., Xu, H., Shao, J., et al.: Polydopamine-functionalized black phosphorus quantum dots for cancer theranostics. Appl. Mater. Today 15, 297–304 (2019). https://doi.org/10.1016/J.APMT.2019.02.002
Li, Y., Tang, J., Pan, D.-X., et al.: A versatile imaging and therapeutic platform based on dual-band luminescent lanthanide nanoparticles toward tumor metastasis inhibition. ACS Nano 10, 2766–2773 (2016). https://doi.org/10.1021/acsnano.5b07873
Chen, G., Ågren, H., Ohulchanskyy, T.Y., Prasad, P.N.: Light upconverting core–shell nanostructures: nanophotonic control for emerging applications. Chem. Soc. Rev. 44, 1680–1713 (2015). https://doi.org/10.1039/C4CS00170B
Zheng, W., Huang, P., Tu, D., et al.: Lanthanide-doped upconversion nano-bioprobes: electronic structures, optical properties, and biodetection. Chem. Soc. Rev. 44, 1379–1415 (2015). https://doi.org/10.1039/C4CS00178H
Lv, R., Yang, D., Yang, P., et al.: Integration of upconversion nanoparticles and ultrathin black phosphorus for efficient photodynamic theranostics under 808 nm near-infrared light irradiation. Chem. Mater. 28, 4724–4734 (2016). https://doi.org/10.1021/acs.chemmater.6b01720
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2020 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Gaddam, S.K., Pothu, R., Saran, A., Boddula, R. (2020). Biomedical Applications of Black Phosphorus. In: Inamuddin, Boddula, R., Asiri, A. (eds) Black Phosphorus. Engineering Materials. Springer, Cham. https://doi.org/10.1007/978-3-030-29555-4_6
Download citation
DOI: https://doi.org/10.1007/978-3-030-29555-4_6
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-29554-7
Online ISBN: 978-3-030-29555-4
eBook Packages: Chemistry and Materials ScienceChemistry and Material Science (R0)