Abstract
In cellular environments, certain synthetic molecules can form nanostructures via self-assembly, impacting molecular imaging, and biomedical applications. Control over the formation of these self-assembled nanostructures in subcellular organelle is challenging. By the action of stimuli, either present in the cellular environment or applied externally, in situ generation of molecular precursors can lead to accumulation and supramolecular nanostructure formation, resulting in efficient bioimaging. Here, we summarize smart fluorophore-based ordered nanostructure preparation at specific organelles for efficient bioimaging and therapeutic application towards cancer theranostics. We also present challenges and an outlook regarding intercellular self-assembly for theranostics appβ¦
Abstract
In cellular environments, certain synthetic molecules can form nanostructures via self-assembly, impacting molecular imaging, and biomedical applications. Control over the formation of these self-assembled nanostructures in subcellular organelle is challenging. By the action of stimuli, either present in the cellular environment or applied externally, in situ generation of molecular precursors can lead to accumulation and supramolecular nanostructure formation, resulting in efficient bioimaging. Here, we summarize smart fluorophore-based ordered nanostructure preparation at specific organelles for efficient bioimaging and therapeutic application towards cancer theranostics. We also present challenges and an outlook regarding intercellular self-assembly for theranostics application. Altogether, smart nanostructured materials with fluorescence read-outs at specific subcellular compartments would be beneficial in synthetic biology and precision therapeutics.
Access this article
Subscribe and save
Springer+
from $39.99 /Month
- Starting from 10 chapters or articles per month
- Access and download chapters and articles from more than 300k books and 2,500 journals
- Cancel anytime
Buy Now
Price excludes VAT (USA) Tax calculation will be finalised during checkout.
Instant access to the full article PDF.
Similar content being viewed by others


Data Availability
No datasets were generated or analysed during the current study.
References
Whitesides GM, Grzybowski B (2002) Self-assembly at all scales. Science 295:2418β2421. https://doi.org/10.1126/science.1070821
Article CAS PubMed Google Scholar 1.
Gazit E (2010) Bioinspired chemistry: diversity for self-assembly. Nat Chem 2:1010β1011. https://doi.org/10.1038/nchem.912
Article CAS PubMed Google Scholar 1.
Schwille P (2011) Bottom-up synthetic biology: engineering in a tinkererβs world. Science 333:1252β1254. https://doi.org/10.1126/science.1211701
Article CAS PubMed Google Scholar 1.
Levin A, Hakala TA, Schnaider L, Bernardes GJL, Gazit E, Knowles TPJ (2020) Biomimetic peptide self-assembly for functional materials. Nat Rev Chem 4:615β634. https://doi.org/10.1038/s41570-020-0215-y
Article CAS PubMed PubMed Central Google Scholar 1.
Tu Y, Peng F, Adawy A, Men Y, Abdelmohsen LKEA, Wilson DA (2016) Mimicking the cell: bio-inspired functions of supramolecular assemblies. Chem Rev 116:2023β2078. https://doi.org/10.1021/acs.chemrev.5b00344
Article CAS PubMed Google Scholar 1.
Yeh BJ, Lim WA (2007) Synthetic biology: lessons from the history of synthetic organic chemistry. Nat Chem Biol 3:521. https://doi.org/10.1038/nchembio0907-521
Article CAS PubMed Google Scholar 1.
Webber MJ, Dankers PYW (2019) Supramolecular hydrogels for biomedical applications. Macromol Biosci 19:e1800452. https://doi.org/10.1002/mabi.201800452
Article CAS PubMed Google Scholar 1.
Vance JA, Devaraj NK (2021) Membrane mimetic chemistry in artificial cells. J Am Chem Soc 143:8223β8231. https://doi.org/10.1021/jacs.1c03436
Article CAS PubMed Google Scholar 1.
Insua I, Montenegro J (2020) Synthetic supramolecular systems in life-like materials and protocell models. Chem 6:1652β1682. https://doi.org/10.1016/j.chempr.2020.06.005
Ariga K, Hill JP, Lee MV, Vinu A, Charvet R, Acharya S (2008) Challenges and breakthroughs in recent research on self-assembly. Sci Technol Adv Mater 9:014109. https://doi.org/10.1088/1468-6996/9/1/014109
Article CAS PubMed PubMed Central Google Scholar 1.
Wang H, Feng Z, Xu B (2017) Bioinspired assembly of small molecules in cell milieu. Chem Soc Rev 46:2421β2436. https://doi.org/10.1039/C6CS00656F
Article CAS PubMed PubMed Central Google Scholar 1.
Du Z, Fan B, Dai Q, Wang L, Guo J, Ye Z, Cui N, Chen J, Tan K, Li R, Tang W (2022) Supramolecular peptide nanostructures: self-assembly and biomedical applications. Giant 9:100082. https://doi.org/10.1016/j.giant.2021.100082
Qi GB, Gao YJ, Wang L, Wang H (2018) Self-assembled peptide-based nanomaterials for biomedical imaging and therapy. Adv Mater 30:1703444. https://doi.org/10.1002/adma.201703444
Longmire M, Choyke PL, Kobayashi H (2008) Clearance properties of nano-sized particles and molecules as imaging agents: considerations and caveats. Nanomedicine (Lond) 3:703β717. https://doi.org/10.2217/17435889.3.5.703
Article CAS PubMed Google Scholar 1.
Lee HJ, Pardridge WM (2003) Monoclonal antibody radiopharmaceuticals: cationization, pegylation, radiometal chelation, pharmacokinetics, and tumor imaging. Bioconjugate Chem 14:546. https://doi.org/10.1021/bc0256648
Brizard AM, van Esch JH (2009) Self-assembly approaches for the construction of cell architecture mimics. Soft Matter 5:1320β1327. https://doi.org/10.1039/B812388H
Froimchuk E, Carey ST, Edwards C, Jewell CM (2020) Self-Assembly as a molecular strategy to improve immunotherapy. Acc Chem Res 53:2534β2545. https://doi.org/10.1021/acs.accounts.0c00438
Article CAS PubMed PubMed Central Google Scholar 1.
Pochan D, Scherman O (2021) Introduction: molecular self-assembly. Chem Rev 121:13699. https://doi.org/10.1021/acs.chemrev.1c00884
Article CAS PubMed Google Scholar 1.
Yan Z, Liu Y, Zhao L, Hu J, Du Y, Peng X, Liu Z (2023) In situ stimulus-responsive self-assembled nanomaterials for drug delivery and disease treatment. Mater Horiz 10:3197β3217. https://doi.org/10.1039/D3MH00592E
Article CAS PubMed Google Scholar 1.
Cheng DB, Wang D, Gao YJ, Wang L, Qiao ZY, Wang H (2019) Autocatalytic morphology transformation platform for targeted drug accumulation. J Am Chem Soc 141:4406β4411. https://doi.org/10.1021/jacs.8b13512
Article CAS PubMed Google Scholar 1.
Ellis RJ (2011) Macromolecular crowding: an important but neglected aspect of the intracellular environment. Curr Opin Struct Biol 11:114β119. https://doi.org/10.1016/S0959-440X(00)00172-X
Chagri S, Ng DYW, Weil T (2022) Designing bioresponsive nanomaterials for intracellular self-assembly. Nat Rev Chem 6:320β338. https://doi.org/10.1038/s41570-022-00373-x
Article PubMed PubMed Central Google Scholar 1.
Liang G, Ren H, Rao J (2009) A biocompatible condensation reaction for controlled assembly of nanostructures in living cells. Nat Chem 2:54β60. https://doi.org/10.1038/nchem.480
Article CAS PubMed Google Scholar 1.
Dragulescu-Andrasi A, Kothapalli SR, Tikhomirov GA, Rao J, Gambhir SS (2013) Activatable oligomerizable imaging agents for photoacoustic imaging of furin- like activity in living subjects. J Am Chem Soc 135:11015β11022. https://doi.org/10.1021/ja4010078
Article CAS PubMed PubMed Central Google Scholar 1.
Cabral H, Nishiyama N, Kataoka K (2011) Supramolecular nanodevices: from design validation to theranostic nanomedicine. Acc Chem Res 44:999β1008. https://doi.org/10.1021/ar200094a
Article CAS PubMed Google Scholar 1.
Dergham M, Lin S, Geng J (2022) Supramolecular self-assembly in living cell. Angew Chem Int Ed 61:e202114267. https://doi.org/10.1002/anie.202114267
Wang Y, Weng J, Wen X, Hu Y, Ye D (2021) Recent advances in stimuli-responsive in situ self-assembly of small molecule probes for in vivo imaging of enzymatic activity. Biomater Sci 9:406β421. https://doi.org/10.1039/D0BM00895H
Article CAS PubMed Google Scholar 1.
He H, Tan W, Guo J, Yi M, Shy AN, Xu B (2020) Enzymatic noncovalent synthesis. Chem Rev 120:9994β10078. https://doi.org/10.1021/acs.chemrev.0c00306
Article CAS PubMed PubMed Central Google Scholar 1.
Liu Z, Guo J, Qiao Y, Xu B. Enzyme-instructed intracellular peptide assemblies. Acc Chem Res 56:3076β3088. https://doi.org/10.1021/acs.accounts.3c00542 1.
Kim J, Lee S, Kim Y, Choi M, Lee I, Kim E, Yoon CG, Pu K, Kang H, Kim JS (2023) In situ self-assembly for cancer therapy and imaging. Nat Rev Mater 8:710β725. https://doi.org/10.1038/s41578-023-00589-3
Hughes M, Debnath S, Knapp CW, Ulijn RV (2013) Antimicrobial properties of enzymatically triggered self-assembling aromatic peptide amphiphiles. Biomater Sci 1:1138β1142. https://doi.org/10.1039/C3BM60135H
Article CAS PubMed Google Scholar 1.
Li LL, An HW, Peng B, Zheng R, Wang H (2019) Self-assembled nanomaterials: design principles, the nanostructural effect, and their functional mechanisms as antimicrobial or detection agents. Mater Horiz 6:1794β1811. https://doi.org/10.1039/C8MH01670D
Zou P, Chen WT, Sun T, Gao Y, Li LL, Wang H (2020) Recent advances: peptides and self-assembled peptide-nanosystems for antimicrobial therapy and diagnosis. Biomater Sci 8:4975β4996. https://doi.org/10.1039/D0BM00789G
Article CAS PubMed Google Scholar 1.
Lohr T, Marks T (2015) Orthogonal tandem catalysis. Nat Chem 7:477β482. https://doi.org/10.1038/nchem.2262
Article CAS PubMed Google Scholar 1.
Zhou J, Li J, Du X, Xu B (2017) Supramolecular biofunctional materials. Biomaterials 129:1β27. https://doi.org/10.1016/j.biomaterials.2017.03.014
Article CAS PubMed PubMed Central Google Scholar 1.
Albertazzi L, Martinez-Veracoechea FJ, Leenders CM, Voets IK, Frenkel D, Meijer EW (2013) Spatiotemporal control and superselectivity in supramolecular polymers using multivalency. Proc Natl Acad Sci USA 110:12203. https://doi.org/10.1073/pnas.1303109110
Article PubMed PubMed Central Google Scholar 1.
Hu Y, Lin R, Patel K, Cheetham AG, Kan C, Cui H (2016) Spatiotemporal control of the creation and immolation of peptide assemblies. Coord Chem Rev 320β321:2β17. https://doi.org/10.1016/j.ccr.2016.02.014
Feng Z, Zhang T, Wang H, Xu B (2017) Supramolecular catalysis and dynamic assemblies for medicine. Chem Soc Rev 46:6470β6479. https://doi.org/10.1039/C7CS00472A
Article CAS PubMed PubMed Central Google Scholar 1.
Uhlenheuer DA, Petkau K, Brunsveld L (2010) Combining supramolecular chemistry with biology. Chem Soc Rev 39:2817β2826. https://doi.org/10.1039/B820283B
Article CAS PubMed Google Scholar 1.
Scinto SL, Bilodeau DA, Hincapie R, Lee W, Nguyen SS, Xu M, Ende CW, Finn MG, Lang K, Lin Q, Pezacki JP, Prescher JA, Robillard MS, Fox JM (2021) Bioorthogonal Chem Nat Rev Methods Prim 1:30. https://doi.org/10.1038/s43586-021-00028-z 1.
Omar J, Ponsford D, Dreiss CA, Lee TC, Loh XJ (2022) Supramolecular hydrogels: design strategies and contemporary biomedical applications. Chem Asian J 17:e202200081. https://doi.org/10.1002/asia.202200081
Article CAS PubMed Google Scholar 1.
Webb BA, Chimenti M, Jacobson MP, Barber DL (2011) Dysregulated pH: a perfect storm for cancer progression. Nat Rev Cancer 11:671β677. https://doi.org/10.1038/nrc3110
Article CAS PubMed Google Scholar 1.
Trachootham D, Alexandre J, Huang P (2009) Targeting cancer cells by ROS- mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov 8:579β591. https://doi.org/10.1038/nrd2803
Article CAS PubMed Google Scholar 1.
Williams RJ, Smith AM, Collins R, Hodson N, Das AK, Ulijn RV (2009) Enzyme-assisted self-assembly under thermodynamic control. Nat Nanotechnol 4:19β24. https://doi.org/10.1038/nnano.2008.378
Article CAS PubMed Google Scholar 1.
Feng Z, Wang H, Chen X, Xu B (2017) Self-assembling ability determines the activity of enzyme-instructed self-assembly for inhibiting cancer cells. J Am Chem Soc 139:15377β15384. https://doi.org/10.1021/jacs.7b07147
Article CAS PubMed PubMed Central Google Scholar 1.
Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646β674. https://doi.org/10.1016/j.cell.2011.02.013
Article CAS PubMed Google Scholar 1.
MartΓnez-Reyes I, Chandel NS (2021) Cancer metabolism: looking forward. Nat Rev Cancer 21:669β680. https://doi.org/10.1038/s41568-021-00378-6
Article CAS PubMed Google Scholar 1.
van Weverwijk A, de Visser KE (2023) Mechanisms driving the immunoregulatory function of cancer cells. Nat Rev Cancer 23:193β215. https://doi.org/10.1038/s41568-022-00544-4
Article CAS PubMed Google Scholar 1.
Gaharwar K, Singh I (2023) A synthetic tumour microenvironment. Nat Mater 22:412β413. https://doi.org/10.1038/s41563-023-01511-6
Article CAS PubMed Google Scholar 1.
Lu Y, Aimetti AA, Langer R, Gu Z (2017) Bioresponsive materials. Nat Rev Mater 2:16075. https://doi.org/10.1038/natrevmats.2016.75
Shah K, McCormack CE, Bradbury NA (2014) Do you know the sex of your cells? Am J Physiol Cell Physiol 306:C3βC18. https://doi.org/10.1152/ajpcell.00281.2013
Article CAS PubMed Google Scholar 1.
Clocchiatti A, Cora E, Zhang Y, Dotto GP (2016) Sexual dimorphism in cancer. Nat Rev Cancer 16:330β339. https://doi.org/10.1038/nrc.2016.30
Article CAS PubMed Google Scholar 1.
Cardano M, Buscemi G, Zannini L (2022) Sex disparities in DNA damage response pathways: novel determinants in cancer formation and therapy. iScience 25:103875. https://doi.org/10.1016/j.isci.2022.103875
Article CAS PubMed PubMed Central Google Scholar 1.
Cardano M, Magni M, Alfieri R, Chan SY, Sabbioneda S, Buscemi G, Zannini L (2023) Sex specific regulation of TSPY-Like 2 in the DNA damage response of cancer cells. Cell Death Dis 14:197. https://doi.org/10.1038/s41419-023-05722-2
Article CAS PubMed PubMed Central Google Scholar 1.
Tristan C, Shahani N, Sedlak TW, Sawa A (2011) The diverse functions of GAPDH: views from different subcellular compartments. Cell Signal 23:317. https://doi.org/10.1016/j.cellsig.2010.08.003
Article CAS PubMed Google Scholar 1.
Li M, Ning Y, Chen J, Duan X, Song N, Ding D, Su X, Yu Z (2019) Proline isomerization-regulated tumor microenvironment-adaptable self-assembly of peptides for enhanced therapeutic efficacy. Nano Lett 19:7965β7976. https://doi.org/10.1021/acs.nanolett.9b03136
Article CAS PubMed Google Scholar 1.
Versluis F, van Elsland DM, Mytnyk S, Perrier DL, Trausel F, Poolman JM, Maity C, le Sage VAA, van Kasteren SI, van Esch JH, Eelkema R (2016) Negatively charged lipid membranes catalyze supramolecular hydrogel formation. J Am Chem Soc 138:8670. https://doi.org/10.1021/jacs.6b03853
Article CAS PubMed Google Scholar 1.
Qiao SL, Ma Y, Wang Y, Lin YX, An HW, Li LL, Wang H (2017) General approach of stimuli-induced aggregation for monitoring tumor therapy. ACS Nano 11:7301β7311. https://doi.org/10.1021/acsnano.7b03375
Article CAS PubMed Google Scholar 1.
Zhou Z, Maxeiner K, Ng DYW, Weil T (2022) Polymer chemistry in living cells. Acc Chem Res 55:2998β3009. https://doi.org/10.1021/acs.accounts.2c00420
Article CAS PubMed PubMed Central Google Scholar 1.
Yuste R (2005) Fluorescence microscopy today. Nat Methods 2:902β904. https://doi.org/10.1038/nmeth1205-902
Article CAS PubMed Google Scholar 1.
Bunt G, Wouters FS (2017) FRET from single to multiplexed signaling events. Biophys Rev 9:119β129. https://doi.org/10.1007/s12551-017-0252-z
Article PubMed PubMed Central Google Scholar 1.
Lippincott-Schwartz J, Snapp E, Kenworthy A (2001) Studying protein dynamics in living cells. Nat Rev Mol Cell Biol 2:444β456. https://doi.org/10.1038/35073068
Article CAS PubMed [Google Scholar](http://scholar.google.com/scholar_lookup?&title=Studying%20protein%20dynamics%20in%20l