Exploration of Targeted Anti-tumor Therapy

Table 2. Fabrication techniques and surface functionalization methods for nanofluidic—DNA origami integration.

Fabrication technique	Resolution (nm)	Substrate compatibility	Key functionalization strategy
Electron-beam lithography (EBL)	10–20	Silicon, silicon nitride, glass	Covalent silanization (e.g., APTES), Au-thiol linkers
Focused ion beam (FIB) milling	20–50	Silicon, glass	Streptavidin-biotin bridges; SAMs on gold-coated surfaces
Nanoimprint lithography (NIL)	~20–100	PDMS, thermoplastics	UV-curable adhesives; layer-by-layer electrostatic assembly
Photolithography + etching	~100–500	Glass, quartz, PMMA	EDC/NHS-mediated amine-carboxyl coupling
Soft lithography (PDMS-based)	~100–1,000	PDMS, glass	Microcontact printing with DNA-modified stamps
3D nanoprinting (two-photon)	~200	Polymer resins	Direct embedding of DNA origami with photopolymerizable anchors

Return to article view

3D: three-dimensional.

Declarations

Author contributions

DS: Conceptualization, Methodology, Investigation, Writing—original draft, Visualization, Supervision, Project administration. SS: Methodology, Formal analysis, Data curation, Writing—review & editing. NT: Validation, Resources, Writing—review & editing. NB: Supervision, Writing—review & editing, Validation. All authors read and approved the submitted version.

Conflicts of interest

The authors declare that there are no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

Publisher’s note

Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

References

Liu H, Fan C. DNA Origami Nanostructures. In: Fan C, editor. DNA Nanotechnology. Berlin, Heidelberg: Springer Berlin Heidelberg; 2013. pp. 207–24. [DOI]

Wang J, Zhang P, Xia Q, Wei Y, Chen W, Wang J, et al. Application of DNA origami in nanobiomedicine. Nan Fang Yi Ke Da Xue Xue Bao. 2021;41:960–4. Chinese. [DOI]

Ruiz DD, Cardos KL, Soto G, Samano EC. Gold nanostructures based on DNA Origami templates with applications in nanoelectronics and plasmonics. MRS Adv. 2017;2:4017–23. [DOI]

Ahmadi Y, De Llano E, Barišić I. (Poly)cation-induced protection of conventional and wireframe DNA origami nanostructures. Nanoscale. 2018;10:7494–504. [DOI] [PubMed]

Chen Z, Lan X, Wang Q. DNA origami directed large-scale fabrication of nanostructures resembling room temperature single-electron transistors. Small. 2013;9:3567–71. [DOI] [PubMed]

Halley P, Roki N, Vantangoli N, Zupancic T, Spitzner J, Long M, et al. Abstract 828: DNA origami nanostructures as a targeted payload delivery system. Cancer Res. 2023;83:828. [DOI]

Jiao Y, Wang H, Wang H, Xie Y, Shang Y, Wu Y, et al. A DNA origami–based enzymatic cascade nanoreactor for chemodynamic cancer therapy and activation of antitumor immunity. Sci Adv. 2025;11:eadr9196. [DOI]

Tandon R, Patil S, Tandon N, Kumar P. Magnetically recyclable silica-coated magnetite-molybdate nanocatalyst and its applications in N-formylation reactions under solvent-free conditions. Lett Org Chem. 2022;19:616–26. [DOI]

Patil SM, Tandon R, Tandon N, Singh I, Bedre A, Gade V. Magnetite-supported montmorillonite (K₁₀) (nanocat-Fe-Si-K₁₀): an efficient green catalyst for multicomponent synthesis of amidoalkyl naphthol. RSC Adv. 2023;13:17051–61. [PubMed] [PMC]

10.

Wei X, Chen C, Popov AV, Bathe M, Hernandez R. Binding Site Programmable Self-Assembly of 3D Hierarchical DNA Origami Nanostructures. J Phys Chem A. 2024;128:4999–5008. [DOI] [PubMed]

11.

Wang C, Xu JJ, Chen HY, Xia XH. Mass transport in nanofluidic devices. Sci China Chem. 2012;55:453–68. [DOI]

12.

Karnik R, Castelino K, Duan C, Fan R, Yang P, Majumdar A. Nanofluidic devices for sensing and flow control. In: ASME 4th International Conference on Nanochannels, Microchannels, and Minichannels, Parts A and B. International Conference on Nanochannels, Microchannels, and Minichannels; 2006 Jun 19-21; Limerick, Ireland. 2006. pp. 161–7. [DOI]

13.

Cui Y, Gao L, Ying C, Tian J, Liu Z. Two-dimensional material-based nanofluidic devices and their applications. ACS Nano. 2025;19:1911–43. [DOI]

14.

Segerink LI, Eijkel JC. Nanofluidics in point of care applications. Lab Chip. 2014;14:3201–5. [DOI] [PubMed]

15.

Eijkel JCT, Sparreboom W, Shui L, Salieb-Beugelaar GB, Van den Berg A. Nanofluidics: Fundamentals and applications. TRANSDUCERS Conf Proc. 2009:1561–5. [DOI]

16.

Dutta P, Morse J. A review of nanofluidic patents. Recent Pat Nanotechnol. 2008;2:150–9. [DOI] [PubMed]

17.

Matthews M, Hill JM. Nanofluidics and the Navier boundary condition. Int J Nanotechnol. 2008;5:218–42. [DOI]

18.

Sheremet MA. Applications of Nanofluids. Nanomaterials. 2021;11:1716. [DOI]

19.

Saidur R, Leong KY, Mohammad HA. A review on applications and challenges of nanofluids. Renew Sust Energ Rev. 2011;15:1646–68. [DOI]

20.

Wang X, Song Y, Li C, Zhang Y, Ali HM, Sharma S, et al. Nanofluids application in machining: a comprehensive review. Int J Adv Manuf Technol. 2024;131:3113–64. [DOI]

21.

Manna I. Synthesis, characterization and application of nanofluid—An overview. J Indian Inst Sci. 2009;89:21–33.

22.

Karmveer, Gupta NK, Alam T. Applications of Nanofluid in the thermal devices: A Review. IOP Conf Ser Mater Sci Eng. 2021;1116:012010. [DOI]

23.

Kumar R, Tiwari A. Heat exchange using nanofluid in solar water heating system. Conf Proc. 2019.

24.

Chaudhari MR, Walke P. A Review on The Application of Nanofluids for Heat Transfer in Automobile Radiator. Conf Proc. 2016.

25.

Harikrishnan S, Dhass AD, Ali HM. Nanofluids. In: Thermal Performance of Nanofluids in Miniature Heat Sinks. Springer; 2022.

26.

Khan IU, Serra CA, Anton N, Vandamme T. Microfluidics: a focus on improved cancer targeted drug delivery systems. J Control Release. 2013;172:1065–74. [DOI] [PubMed]

27.

Martins JP, Liu D, Fontana F, Ferreira MPA, Correia A, Valentino S, et al. Microfluidic Nanoassembly of Bioengineered Chitosan-Modified FcRn-Targeted Porous Silicon Nanoparticles @ Hypromellose Acetate Succinate for Oral Delivery of Antidiabetic Peptides. ACS Appl Mater Interfaces. 2018;10:44354–67. [DOI] [PubMed]

28.

Ren L, Liu S, Zhong J, Zhang L. Revolutionizing targeting precision: microfluidics-enabled smart microcapsules for tailored delivery and controlled release. Lab Chip. 2024;24:1367–93. [DOI] [PubMed]

29.

Alavi SE, Alharthi S, Alavi SF, Alavi SZ, Zahra GE, Raza A, et al. Microfluidics for personalized drug delivery. Drug Discov Today. 2024;29:103936. [DOI] [PubMed]

30.

Rawas-Qalaji M, Cagliani R, Al-Hashimi N, Al-Dabbagh R, Al-Dabbagh A, Hussain Z. Microfluidics in drug delivery: review of methods and applications. Pharm Dev Technol. 2023;28:61–77. [DOI] [PubMed]

31.

Bose N, Zhang X, Maiti TK, Chakraborty S. The role of acoustofluidics in targeted drug delivery. Biomicrofluidics. 2015;9:052609. [DOI] [PubMed] [PMC]

32.

Schuster B, Junkin M, Kashaf SS, Romero-Calvo I, Kirby K, Matthews J, et al. Automated microfluidic platform for dynamic and combinatorial drug screening of tumor organoids. Nat Commun. 2020;11:5271. [DOI]

33.

Zhang Q, Kuang G, Wang L, Fan L, Zhao Y. Tailoring drug delivery systems by microfluidics for tumor therapy. Mater Today. 2024;73:151–78. [DOI]

34.

Teixeira MI, Amaral MH, Costa PC, Lopes CM, Lamprou DA. Recent Developments in Microfluidic Technologies for Central Nervous System Targeted Studies. Pharmaceutics. 2020;12:542. [DOI] [PubMed] [PMC]

35.

Liu A, Islam M, Stone N, Varadarajan V, Jeong J, Bowie S, et al. Microfluidic generation of transient cell volume exchange for convectively driven intracellular delivery of large macromolecules. Mater Today (Kidlington). 2018;21:703–12. [DOI] [PubMed] [PMC]

36.

Boussommier-Calleja A, Li R, Chen MB, Wong SC, Kamm RD. Microfluidics: A new tool for modeling cancer-immune interactions. Trends Cancer. 2016;2:6–19. [DOI] [PubMed] [PMC]

37.

Ramirez A, Amosu M, Lee P, Maisel K. Microfluidic systems to study tissue barriers to immunotherapy. Drug Deliv Transl Res. 2021;11:2414–29. [DOI] [PubMed] [PMC]

38.

Trucillo P. Biomaterials for Drug Delivery and Human Applications. Materials (Basel). 2024;17:456. [DOI] [PubMed] [PMC]

39.

Prestwich GD, Luo Y. Novel biomaterials for drug delivery. Expert Opin Ther Pat. 2001;11:1395–410. [DOI]

40.

Fenton OS, Olafson KN, Pillai PS, Mitchell MJ, Langer R. Advances in Biomaterials for Drug Delivery. Adv Mater. 2018;30:1705328. [DOI] [PubMed] [PMC]

41.

Chen JC, Li LM, Gao JQ. Biomaterials for local drug delivery in central nervous system. Int J Pharm. 2019;560:92–100. [DOI] [PubMed]

42.

Caliceti P, Matricardi P. Advances in Drug Delivery and Biomaterials: Facts and Vision. Pharmaceutics. 2019;11:48. [DOI] [PubMed] [PMC]

43.

Stejskalová A, Kiani MT, Almquist BD. Programmable biomaterials for dynamic and responsive drug delivery. Exp Biol Med (Maywood). 2016;241:1127–37. [DOI] [PubMed] [PMC]

44.

Gokhale A, Williams T, Vaughn J. Nanoparticles: Biomaterials for Drug Delivery. In: Encyclopedia of Biomedical Polymers and Polymeric Biomaterials, 11 Volume Set. 1st Edition. Boca Raton: CRC Press. 2015.

45.

Overstreet DJ, Von Recum HA, Vernon BL. 5 - Drug delivery applications of injectable biomaterials. In: Vernon B, editor. Injectable Biomaterials. Woodhead Publishing; 2011. pp. 95–141. [DOI]

46.

Buckles RG. Biomaterials for drug delivery systems. J Biomed Mater Res. 1983;17:109–28. [DOI]

47.

Singh C, Ali SSA. Innovative drug delivery systems from aquatic biomaterials: a new era in medical treatment. J Neonatal Surg. 2025;14:433–6. [DOI]

48.

Paterson K, Zagnoni M. Microfluidic Protocols for the Assessment of Anticancer Therapies in 3D Tumor-Stromal Cocultures. Methods Mol Biol. 2023;2679:127–39.

49.

Paterson K, Zanivan S, Glasspool R, Coffelt SB, Zagnoni M. Microfluidic technologies for immunotherapy studies on solid tumours. Lab Chip. 2021;21:2306–29. [DOI] [PubMed] [PMC]

50.

Wang Y, Jin R, Shen B, Li N, Zhou H, Wang W, et al. High-throughput functional screening for next-generation cancer immunotherapy using droplet-based microfluidics. Sci Adv. 2021;7. [DOI]

51.

Li Y, Fan H, Ding J, Xu J, Liu C, Wang H. Microfluidic devices: The application in TME modeling and the potential in immunotherapy optimization. Front Genet. 2022;13. [DOI]

52.

Ngan Ngo TK, Kuo CH, Tu TY. Recent advances in microfluidic-based cancer immunotherapy-on-a-chip strategies. Biomicrofluidics. 2023;17:011501. [DOI] [PubMed] [PMC]

53.

Xie H, Appelt JW, Jenkins RW. Going with the Flow: Modeling the Tumor Microenvironment Using Microfluidic Technology. Cancers (Basel). 2021;13:6052. [DOI] [PubMed] [PMC]

54.

Briones J, Espulgar W, Koyama S, Takamatsu H, Tamiya E, Saito M. The future of microfluidics in immune checkpoint blockade. Cancer Gene Ther. 2021;28:895–910. [DOI] [PubMed]

55.

Parlato S, De Ninno A, Molfetta R, Toschi E, Salerno D, Mencattini A, et al. 3D Microfluidic model for evaluating immunotherapy efficacy by tracking dendritic cell behaviour toward tumor cells. Sci Rep. 2017;7:1093. [DOI] [PubMed] [PMC]

56.

Caballero D, Abreu CM, Reis RL, Kundu SC. Emerging Microfluidic and Biosensor Technologies for Improved Cancer Theranostics. Adv Exp Med Biol. 2022;1379:461–95. [DOI] [PubMed]

57.

Wang Y, Gao W, Wu M, Zhang X, Liu W, Zhou Y, et al. EGFR mutation detection of lung circulating tumor cells using a multifunctional microfluidic chip. Talanta. 2021;225:122057. [DOI] [PubMed]

58.

Liu W, Sun M, Lu B, Yan M, Han K, Wang J. A microfluidic platform for multi-size 3D tumor culture, monitoring and drug resistance testing. Sens Actuators B Chem. 2019;292:111–20. [DOI]

59.

Maher S, Santos A, Kumeria T, Kaur G, Lambert M, Forward P, et al. Multifunctional microspherical magnetic and pH responsive carriers for combination anticancer therapy engineered by droplet-based microfluidics. J Mater Chem B. 2017;5:4097–109. [DOI] [PubMed]

60.

Zhang H. Multifunctional nanomedicine platforms for cancer therapy. J Nanosci Nanotechnol. 2012;12:4012–8. [DOI] [PubMed]

61.

Zhang Y, Sun M, Zhou H, Zhang Y, Qiu J, Cheng X, et al. Microfluidic biosensing platform integrated with flexible sensing array for cancer biomarker point-of-care testing. Sens Actuators B Chem. 2025;427:137148. [DOI]

62.

Liu W, Liu D, Hu R, Huang Z, Sun M, Han K. An integrated microfluidic 3D tumor system for parallel and high-throughput chemotherapy evaluation. Analyst. 2020;145:6447–55. [DOI] [PubMed]

63.

Luo M, Yukawa H, Baba Y. Micro-/nano-fluidic devices and in vivo fluorescence imaging based on quantum dots for cytologic diagnosis. Lab Chip. 2022;22:2223–36. [DOI] [PubMed]

64.

Luan X, Gao Y, Pan Y, Huang Z, Zeng F, He G, et al. Bifunctional Nanoassembly Enables Metabolism-Driven Microfluidic Blood Screening Guided by MRI Localization for Cancer Monitoring. Anal Chem. 2025;97:3395–403. [DOI] [PubMed]

65.

Singh A, Iyer AK, Amiji M, Ganta S. 14 - Multifunctional nanosystems for cancer therapy. In: Park K, editor. Biomaterials for Cancer Therapeutics. Woodhead Publishing; 2013. pp. 387–413. [DOI]

66.

Vinod AV, Bolledla NR. Microfluidics of Nanodrug Delivery at Different Angles of Drug Injection. Chem Prod Process Model. 2010;5:1. [DOI]

67.

Kleinstreuer C, Li J, Koo J. Microfluidics of nano-drug delivery. Int J Heat Mass Transf. 2008;51:5590–7. [DOI]

68.

Cannon DM, Kuo T, Bohn PW, Sweedler JV. Nanocapillary Array Interconnects for Gated Analyte Injections and Electrophoretic Separations in Multilayer Microfluidic Architectures. Anal Chem. 2003;75:2224–30. [DOI]

69.

Liu K, Zhu Z, Wang X, Gonçalves D, Zhang B, Hierlemann A, et al. Microfluidics-based single-step preparation of injection-ready polymeric nanosystems for medical imaging and drug delivery. Nanoscale. 2015;7:16983–93. [DOI] [PubMed]

70.

Chua CYX, Jain P, Susnjar A, Rhudy J, Folci M, Ballerini A, et al. Nanofluidic drug-eluting seed for sustained intratumoral immunotherapy in triple negative breast cancer. J Control Release. 2018;285:23–34. [DOI] [PubMed]

71.

Pons-Faudoa FP, Sizovs A, Di Trani N, Paez-Mayorga J, Bruno G, Rhudy J, et al. 2-Hydroxypropyl-β-cyclodextrin-enhanced pharmacokinetics of cabotegravir from a nanofluidic implant for HIV pre-exposure prophylaxis. J Control Release. 2019;306:89–96. [DOI] [PubMed] [PMC]

72.

Ma Q, Cao J, Gao Y, Han S, Liang Y, Zhang T, et al. Microfluidic-mediated nano-drug delivery systems: from fundamentals to fabrication for advanced therapeutic applications. Nanoscale. 2020;12:15512–27. [DOI] [PubMed]

73.

Yun CK, Hwang JW, Kwak TJ, Chang WJ, Ha S, Han K, et al. Nanoinjection system for precise direct delivery of biomolecules into single cells. Lab Chip. 2019;19:580–8. [DOI] [PubMed]

74.

Siddique S, Chow JCL. Application of Nanomaterials in Biomedical Imaging and Cancer Therapy. Nanomaterials (Basel). 2020;10:1700. [DOI] [PubMed] [PMC]

75.

Chow JCL. Biophysical insights into nanomaterial-induced DNA damage: mechanisms, challenges, and future directions. AIMS Biophys. 2024;11:340–69. [DOI]

76.

Joo JU, Na GS, Sharma V, Mottafegh A, Kim DP. Ultrafast continuous flow-dialysis for nanoparticle-based drug delivery systems via microfluidic-multiple buffer injector. Chem Eng J. 2024;500:156631. [DOI]

77.

Chon CH, Kim JH, On H, Choi J, Lee S, Han E. A microfluidic application for mass production of drug-loaded polymeric microspheres for a long-acting injectable with IVL-DrugFluidic®, a novel microfluidic microsphere manufacturing platform technology. OpenNano. 2023;12:100153. [DOI]

78.

Fontana F, Martins JP, Torrieri G, Santos H. Nuts and Bolts: Microfluidics for the Production of Biomaterials. Adv Mater Technol. 2019;4:1800611. [DOI]

79.

Chen Z, Lv Z, Zhang Z, Zhang Y, Cui W. Biomaterials for microfluidic technology. Mater Futures. 2022;1:012401. [DOI]

80.

Ma J, Wang Y, Liu J. Biomaterials Meet Microfluidics: From Synthesis Technologies to Biological Applications. Micromachines (Basel). 2017;8:255. [DOI] [PubMed] [PMC]

81.

Stroock AD, Cabodi M. Microfluidic Biomaterials. MRS Bull. 2006;31:114–9. [DOI]

82.

Giridharan V, Yun Y, Hajdú P, Conforti L, Collins B, Jang Y. Microfluidic platforms for evaluation of nanobiomaterials: a review. J Nanomater. 2012;2012:789841. [DOI]