Architectural fabrication of multifunctional janus nanostructures for biomedical applications

Document Type : Review Paper


1 Medical Bionanotechnology, Faculty of Allied Health Sciences, Chettinad Hospital & Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai-603 103, India

2 Department of Chemistry and Biochemistry, Georgia Southern University, Statesboro, GA 30460


The domain of Janus nanoparticles (JNPs) has seen a surge in research and development during the last decade. JNPs are anisotropic composite innovations with remarkable characteristics that depict a peculiar class of particles, which integrate the features and functions of multiple materials into a single unit. Janus particles are superior prospects for several high-end applications due to their possible modifications by “click chemistry”. JNPs offer new possibilities by combining the features of components. Janus nanoparticles can pack multiple pharmaceuticals and imaging contrast agents simultaneously since they have a distinct chemical configuration on different sides. As a result, they become ideal for administration and bioimaging at once. They have sparked interest due to their exceptional architecture and their potential implications in science and engineering, biological application, and most notably, theranostics. The emphasis of this review is on the latest advancement in the fabrication and implementation of innovative Janus nanoparticles, along with their spectacular performance in therapeutic delivery applications. 


1.    Girigoswami A, Yassine W, Sharmiladevi P, Haribabu V, Girigoswami K. Camouflaged nanosilver with excitation wavelength dependent high quantum yield for targeted theranostic. Sci Rep. 2018;8(1):1-7.
2.    Haribabu V, Sharmiladevi P, Akhtar N, Farook AS, Girigoswami K, Girigoswami A. Label free ultrasmall fluoromagnetic ferrite-clusters for targeted cancer imaging and drug delivery. Curr Drug Del. 2019;16(3):233-241.
3.    Sharmiladevi P, Akhtar N, Haribabu V, Girigoswami K, Chattopadhyay S, Girigoswami A. Excitation wavelength independent carbon-decorated ferrite nanodots for multimodal diagnosis and stimuli responsive therapy. ACS Applied Bio Materials. 2019;2(4):1634-1642.
4.    Sharmiladevi P, Girigoswami K, Haribabu V, Girigoswami A. Nano-enabled theranostics for cancer. Mater Adv. 2021;2:2876-2891.
5.    Jhaveri J, Raichura Z, Khan T, Momin M, Omri A. Chitosan nanoparticles-insight into properties, functionalization and applications in drug delivery and theranostics. Molecules. 2021;26(2):272.
6.    Zhang L, Zhang M, Zhou L, Han Q, Chen X, Li S, et al. Dual drug delivery and sequential release by amphiphilic Janus nanoparticles for liver cancer theranostics. Biomaterials. 2018;181:113-125.
7.    Sharmiladevi P, Breghatha M, Dhanavardhini K, Priya R, Girigoswami K, Girigoswami A. Efficient Wormlike Micelles for the Controlled Delivery of Anticancer Drugs. Nanosci Nanotechnol Asia. 2021;11(3):350-356.
8.    Sau TK, Rogach AL. Nonspherical noble metal nanoparticles: colloid‐chemical synthesis and morphology control. Adv Mater. 2010;22(16):1781-1804.
9.    Hu J, Zhou S, Sun Y, Fang X, Wu L. Fabrication, properties and applications of Janus particles. Chem Soc Rev. 2012;41(11):4356-4378.
10.    De France K, Zeng Z, Wu T, Nyström G. Functional materials from nanocellulose: utilizing structure–property relationships in bottom‐up fabrication. Adv Mater. 2021;33(28):2000657.
11.    Xu W, Tu B, Liu Q, Shu Y, Liang C-C, Diercks CS, et al. Anisotropic reticular chemistry. Nat Rev Mater. 2020;5(10):764-779.
12.    Casagrande C, Fabre P, Raphael E, Veyssié M. “Janus beads”: realization and behaviour at water/oil interfaces. EPL Europhys Lett. 1989;9(3):251.
13.    Su H, Price C-AH, Jing L, Tian Q, Liu J, Qian K. Janus particles: design, preparation, and biomedical applications. Mater Today Bio. 2019;4:100033.
14.    Ha M, Kim J-H, You M, Li Q, Fan C, Nam J-M. Multicomponent plasmonic nanoparticles: from heterostructured nanoparticles to colloidal composite nanostructures. Chem Rev. 2019;119(24):12208-12278.
15.    Tran L-T-C, Lesieur S, Faivre V. Janus nanoparticles: materials, preparation and recent advances in drug delivery. Expert Opin Drug Deliv 2014;11(7):1061-1074.
16.    Zhang X, Fu Q, Duan H, Song J, Yang H. Janus nanoparticles: from fabrication to (bio) applications. ACS nano. 2021;15(4):6147-6191.
17.    Biswas S, Pramanik S, Mandal S, Sarkar S, Chaudhuri S, De S. Facile synthesis of asymmetric patchy Janus Ag/Cu particles and study of their antifungal activity. Front Mater Sci. 2020;14(1):24-32.
18.    Zhang W, Choi H, Yu B, Kim D-H. Synthesis of iron oxide nanocube patched Janus magnetic nanocarriers for cancer therapeutic applications. Chem Commun. 2020;56(62):8810-8813.
19.    Şologan M, Marson D, Polizzi S, Pengo P, Boccardo S, Pricl S, et al. Patchy and Janus nanoparticles by self-organization of mixtures of fluorinated and hydrogenated alkanethiolates on the surface of a gold core. ACS Nano. 2016;10(10):9316-9325.
20.    McConnell MD, Kraeutler MJ, Yang S, Composto RJ. Patchy and multiregion janus particles with tunable optical properties. Nano Lett. 2010;10(2):603-609.
21.    Chen X, Zhang X, Zhang L, Gao Y, Wang C, Hong W, et al. Amphiphilic Janus nanoparticles for imaging-guided synergistic chemo-photothermal hepatocellular carcinoma therapy in the second near-infrared window. Nanoscale. 2021;13(7):3974-3982.
22.    Kemel K, Deniset-Besseau A, Baillet-Guffroy A, Faivre V, Dazzi A, Laugel C. Nanoscale investigation of human skin and study of skin penetration of Janus nanoparticles. Int J Pharm. 2020;579:119193.
23.    Li X, Zhou L, Wei Y, El-Toni AM, Zhang F, Zhao D. Anisotropic growth-induced synthesis of dual-compartment Janus mesoporous silica nanoparticles for bimodal triggered drugs delivery. J Am Chem Soc. 2014;136(42):15086-15092.
24.    Truong-Cong T, Millart E, Amenitsch H, Frebourg G, Lesieur S, Faivre V. A scalable process to produce lipid-based compartmented Janus nanoparticles with pharmaceutically approved excipients. Nanoscale. 2018;10(8):3654-3662.
25.    Yang T, Wei L, Jing L, Liang J, Zhang X, Tang M, et al. Dumbbell‐Shaped Bi‐Component Mesoporous Janus Solid Nanoparticles for Biphasic Interface Catalysis. Angew Chem Int Ed. 2017;56(29):8459-8463.
26.    Wei C, Du Y, Liu Y, Lin X, Zhang C, Yao J, et al. Organic Janus microspheres: A general approach to all-color dual-wavelength microlasers. J Am Chem Soc. 2019;141(13):5116-5120.
27.    Zhang L, Li S, Chen X, Wang T, Li L, Su Z, et al. Tailored surfaces on 2D material: UFO‐like cyclodextrin‐Pd nanosheet/metal organic framework Janus nanoparticles for synergistic cancer therapy. Adv Funct Mater. 2018;28(51):1803815.
28.    Schick I, Lorenz S, Gehrig D, Tenzer S, Storck W, Fischer K, et al. Inorganic Janus particles for biomedical applications. Beilstein J Nanotechnol 2014;5(1):2346-2362.
29.    Xue W, Yang H, Du Z. Synthesis of pH-responsive inorganic Janus nanoparticles and experimental investigation of the stability of their Pickering emulsions. Langmuir. 2017;33(39):10283-10290.
30.    Ma X, Wang Y, Liu X-L, Ma H, Li G, Li Y, et al. Fe 3O4–Pd Janus nanoparticles with amplified dual-mode hyperthermia and enhanced ROS generation for breast cancer treatment. Nanoscale Horiz. 2019;4(6):1450-1459.
31.    Zhang D, Lin Z, Lan S, Sun H, Zeng Y, Liu X. The design of Janus black phosphorus quantum dots@ metal–organic nanoparticles for simultaneously enhancing environmental stability and photodynamic therapy efficiency. Mater Chem Front. 2019;3(4):656-663.
32.    Wang X, Guan B, He Y, Zhang Y, Cao Y, Liu Y, et al. Synthesis of Janus Mesoporous Silica Nanostructures with Organic–Inorganic Hybrid Components through a Sprout‐Like Growth Method. Chem Nano Mat. 2015;1(8):562-566.
33.    Zhang X, Li ZW, Wu Y, Ge X, Su L, Feng H, et al. Highly Controlled Janus Organic‐Inorganic Nanocomposite as a Versatile Photoacoustic Platform. Angew Chem Int Ed. 2021;133(32):17788-94.
34.    Ali N, Zhang B, Zhang H, Zaman W, Li W, Zhang Q. Key synthesis of magnetic Janus nanoparticles using a modified facile method. Particuology. 2014;17:59-65.
35.    Deng R, Li H, Zhu J, Li B, Liang F, Jia F, et al. Janus nanoparticles of block copolymers by emulsion solvent evaporation induced assembly. Macromolecules. 2016;49(4):1362-1368.
36.    Zhang M, Jiang Y, Qi K, Song Y, Li L, Zeng J, et al. Precise engineering of acorn-like Janus nanoparticles for cancer theranostics. Acta Biomater. 2021;130:423-434.
37.    Xing Y, Zhou Y, Zhang Y, Zhang C, Deng X, Dong C, et al. Facile fabrication route of janus gold-mesoporous silica nanocarriers with dual-drug delivery for tumor therapy. ACS Biomater. Sci. Eng. 2020;6(3):1573-1581.
38.    Jing J, Jiang B, Liang F, Yang Z. Bottlebrush-colloid Janus nanoparticles. ACS Macro Lett. 2019;8(6):737-742.
39.    Kadam R, Ghawali J, Waespy M, Maas M, Rezwan K. Janus nanoparticles designed for extended cell surface attachment. Nanoscale. 2020;12(36):18938-18949.
40.    Dehghani E, Barzgari-Mazgar T, Salami-Kalajahi M, Kahaie-Khosrowshahi A. A pH-controlled approach to fabricate electrolyte/non-electrolyte janus particles with low cytotoxicity as carriers of DOX. Mater Chem Phys. 2020;249:123000.
41.    Zhou L, Zhang H, Bao H, Wei Y, Fu H, Cai W. Monodispersed Snowman-Like Ag-MoS2 Janus Nanoparticles as Chemically Self-Propelled Nanomotors. ACS Appl Nano Maters. 2019;3(1):624-632.
42.    Yan W, Pan M, Yuan J, Liu G, Cui L, Zhang G, et al. Raspberry-like patchy particles achieved by decorating carboxylated polystyrene cores with snowman-like poly (vinylidene fluoride)/poly (4-vinylpyridiene) Janus particles. Polymer. 2017;122:139-147.
43.    Zhang J, Grzybowski BA, Granick S. Janus particle synthesis, assembly, and application. Langmuir. 2017;33(28):6964-6977.
44.    Fu J, An D, Song Y, Wang C, Qiu M, Zhang H. Janus nanoparticles for cellular delivery chemotherapy: Recent advances and challenges. Coord Chem Rev. 2020;422:213467.
45.    Wen W, Chen A. The self-assembly of single chain Janus nanoparticles from azobenzene-containing block copolymers and reversible photoinduced morphology transitions. Polym Chem. 2021;12(16):2447-2456.
46.    Kang C, Honciuc A. Versatile triblock Janus nanoparticles: synthesis and self-assembly. Chem Mater. 2019;31(5):1688-1695.
47.    Lu JE, Yang C-H, Wang H, Yam C, Yu Z-G, Chen S. Plasmonic circular dichroism of vesicle-like nanostructures by the template-less self-assembly of achiral Janus nanoparticles. Nanoscale. 2018;10(30):14586-14593.
48.    Tran N, Mulet X, Hawley AM, Conn CE, Zhai J, Waddington LJ, et al. First direct observation of stable internally ordered janus nanoparticles created by lipid self-assembly. Nano Lett. 2015;15(6):4229-4233.
49.    Kloberg MJ, Yu H, Groß E, Eckmann F, Restle TM, Fässler TF, et al. Surface‐Anisotropic Janus Silicon Quantum Dots via Masking on 2D Silicon Nanosheets. Adv Mater. 2021;33(38):2100288.
50.    Mayol B, Díez P, Sánchez A, de la Torre C, Villalonga A, Lucena-Sánchez E, et al. A glutathione disulfide-sensitive Janus nanomachine controlled by an enzymatic AND logic gate for smart delivery. Nanoscale. 2021;13(44):18616-18625.
51.    Ghanbarinia Firozjah R, Sadeghi A, Khoee S. Ultrasonic De-cross-linking of the pH-and Magneto-Responsive PHEMA/PMMA Microgel to Janus Nanoparticles: A New Synthesis Based on “Grafting from”/“Grafting to” Polymerization. ACS Omega. 2020;5(42):27119-32.
52.    Papan J, Boštjančič PH, Mertelj A, Lisjak D. Preparation of Barium-Hexaferrite/Gold Janus Nanoplatelets Using the Pickering Emulsion Method. Nanomater. 2021;11(11):2797.
53.53.    Khoee S, Keivanshokouh A. Anisotropic modification of SPIONs surface with thiol and alkyne groups for fabrication of poly (2-hydroxyethyl methacrylate)/polydopamine amphiphilic Janus nanoparticles via double-click reaction. Colloid Surf A Physicochem Eng Asp. 2020;597:124777.
54.    Paniagua G, Villalonga A, Eguílaz M, Vegas B, Parrado C, Rivas G, et al. Amperometric aptasensor for carcinoembryonic antigen based on the use of bifunctionalized Janus nanoparticles as biorecognition-signaling element. Anal Chim Acta. 2019;1061:84-91.
55.    Urban M, Freisinger B, Ghazy O, Staff R, Landfester K, Crespy D, et al. Polymer Janus nanoparticles with two spatially segregated functionalizations. Macromolecules. 2014;47(20):7194-7199.
56.    Teo BM, Suh SK, Hatton TA, Ashokkumar M, Grieser F. Sonochemical synthesis of magnetic Janus nanoparticles. Langmuir. 2011;27(1):30-33.
57.    Dehghani E, Salami-Kalajahi M, Roghani-Mamaqani H. Simultaneous two drugs release form Janus particles prepared via polymerization-induced phase separation approach. Colloids Surf B Biointerfaces. 2018;170:85-91.
58.    Zhang Z, Li H, Huang X, Chen D. Solution-based thermodynamically controlled conversion from diblock copolymers to Janus nanoparticles. ACS Macro Lett. 2017;6(6):580-585.
59.    Wu D, Chew JW, Honciuc A. Polarity reversal in homologous series of surfactant-free Janus nanoparticles: toward the next generation of amphiphiles. Langmuir. 2016;32(25):6376-6386.
60.    Lee J, Sands I, Zhang W, Zhou L, Chen Y. DNA-inspired nanomaterials for enhanced endosomal escape. Proc Natl Acad Sci USA 2021;118(19).
61.    Khezrian S, Khoee S, Caceres M. Synthesis of combinatorial Janus nanoparticles based on EpCAM‐PEG/PCL for targeted therapy of human colorectal adenocarcinoma. J Biomed Mater Res A. 2020;108(11):2291-2304.
62.    Zhang D, Atochina-Vasserman EN, Maurya DS, Huang N, Xiao Q, Ona N, et al. One-Component Multifunctional Sequence-Defined Ionizable Amphiphilic Janus Dendrimer Delivery Systems for mRNA. J Am Chem Soc. 2021;143(31):12315-12327.
63.    Shaghaghi B, Khoee S, Bonakdar S. Preparation of multifunctional Janus nanoparticles on the basis of SPIONs as targeted drug delivery system. Int J Pharm. 2019;559:1-12.
64.    Hernandez Montoto A, Llopis‐Lorente A, Gorbe M, M. Terrés J, Cao‐Milán R, Diaz de Grenu B, et al. Janus Gold Nanostars–Mesoporous Silica Nanoparticles for NIR‐Light‐Triggered Drug Delivery. Chem Eur J. 2019;25(36):8471-8478.
65.    Llopis-Lorente A, Garcia-Fernandez A, Murillo-Cremaes N, Hortelao AC, Patino T, Villalonga R, et al. Enzyme-powered gated mesoporous silica nanomotors for on-command intracellular payload delivery. ACS Nano. 2019;13(10):12171-12183.
66.    Wang H, Li S, Zhang L, Chen X, Wang T, Zhang M, et al. Tunable fabrication of folic acid-Au@ poly (acrylic acid)/mesoporous calcium phosphate Janus nanoparticles for CT imaging and active-targeted chemotherapy of cancer cells. Nanoscale. 2017;9(38):14322-14326.
67.    Tamarov K, Sviridov A, Xu W, Malo M, Andreev V, Timoshenko V, et al. Nano air seeds trapped in mesoporous janus nanoparticles facilitate cavitation and enhance ultrasound imaging. ACS Appl. Mater. Interfaces. 2017;9(40):35234-35243.
68.    Deka K, Guleria A, Kumar D, Biswas J, Lodha S, Kaushik SD, et al. Janus nanoparticles for contrast enhancement of T 1–T 2 dual mode magnetic resonance imaging. Dalton Trans. 2019;48(3):1075-1083.
69.    Iqbal MZ, Ren W, Saeed M, Chen T, Ma X, Yu X, et al. A facile fabrication route for binary transition metal oxide-based Janus nanoparticles for cancer theranostic applications. Nano Research. 2018;11(10):5735-5750.
70.    Li S, Zhang L, Chen X, Wang T, Zhao Y, Li L, et al. Selective growth synthesis of ternary janus nanoparticles for imaging-guided synergistic chemo-and photothermal therapy in the second NIR window. ACS Appl. Mater. Interfaces. 2018;10(28):24137-24148.
71.    Ju Y, Zhang H, Yu J, Tong S, Tian N, Wang Z, et al. Monodisperse Au–Fe2C Janus nanoparticles: an attractive multifunctional material for triple-modal imaging-guided tumor photothermal therapy. ACS Nano. 2017;11(9):9239-9248.
72.    Li D, Bao A, Chen X, Li S, Wang T, Zhang L, et al. Prussian Blue@ Polyacrylic Acid/Au Aggregate Janus Nanoparticles for CT Imaging‐guided Chemotherapy and Enhanced Photothermal Therapy. Adv Ther. 2020;3(10):2000091.