Biyomedikal Uygulamalar için Nanoyapılı Bor Bileşikleri: İlaç Dağıtımı, Görüntüleme ve Kanser Tedavisi

Öz

Nanoyapılı bor bileşikleri, özellikle ilaç uygulaması, görüntüleme ve kanser tedavisi gibi biyolojik uygulamalarda önemli potansiyele sahip çok işlevli malzemeler olarak ortaya çıkmıştır. Yükseltilmiş yüzey alanı, ayarlanabilir şekil, kimyasal stabilite ve biyouyumluluk gibi ayırt edici fizikokimyasal özellikleri, onları gelişmiş nanotaşıyıcılar ve terapötik ilaçların geliştirilmesi için uygun hale getirir. Yukarıdan aşağıya ve aşağıdan yukarıya prosedürleri kapsayan çeşitli sentez metodolojileri, boyut, şekil ve işlevin titizlikle düzenlenmesine olanak tanır. Bu bileşikler, hedefli ilaç dağıtımında, multimodal görüntüleme için kontrast artırmada ve bor nötron yakalama terapisi (BNCT) dahil olmak üzere tümör seçici tedavilerde etkili işlevsellik sergiler. Ayrıca, tek bir platformda çeşitli terapötik ve tanısal aktiviteleri birleştirme kapasiteleri, onları kombinasyon ve terapötik stratejiler için örnek adaylar haline getirir. Toksisite, düzenleyici çerçeveler ve ölçeklenebilir üretimle ilgili mevcut engellere rağmen, devam eden disiplinlerarası araştırmaların klinik uygulamalarını kolaylaştırması ve özelleştirilmiş tıpta uygulamalarını geliştirmesi beklenmektedir. Bu derlemenin amacı, nanoyapılı bor bileşiklerinin özelliklerini, sentez yöntemlerini, biyomedikal uygulamalarını ve güncel zorluklarını kapsamlı bir şekilde incelemek ve bunların kişiselleştirilmiş tedavinin geleceğindeki potansiyel rolünü vurgulamaktır.

Anahtar Kelimeler

• Biyouyumluluk
• Drug delivery
• Nanostructured boron

Nanostructured Boron Compounds for Biomedical Applications: Drug Delivery, Imaging, and Cancer Therapy

Öz

Nanostructured boron compounds have arisen as multifunctional materials with considerable potential in biological applications, especially in drug administration, imaging, and cancer treatment. Their distinctive physicochemical characteristics, such as elevated surface area, adjustable shape, chemical stability, and biocompatibility, render them appropriate for the development of improved nanocarriers and therapeutic medicines. Diverse synthesis methodologies, encompassing top-down and bottom-up procedures, permit meticulous regulation of size, shape, and functioning. These compounds exhibit effective functionality in targeted drug delivery, contrast enhancement for multimodal imaging, and tumor-selective therapies, including boron neutron capture therapy (BNCT). Furthermore, their capacity to amalgamate several therapeutic and diagnostic activities within a singular platform renders them exemplary candidates for combination and theranostic strategies. Notwithstanding existing hurdles concerning toxicity, regulatory frameworks, and scalable production, ongoing interdisciplinary research is anticipated to facilitate their clinical translation and enhance their application in customized medicine. This review aims to comprehensively examine the properties, synthesis methods, biomedical applications, and current challenges of nanostructured boron compounds, highlighting their potential role in the future of personalized therapy.

Anahtar Kelimeler

• Nanostructured boron;
• Drug delivery
• Biocompatibility

Kaynakça

1. S. O. Oloo, K. M. Smith, and M. da G. H. Vicente, “Multi-Functional Boron-Delivery Agents for Boron Neutron Capture Therapy of Cancers.,” Cancers (Basel)., vol. 15, no. 13, Jun. 2023, doi: 10.3390/cancers15133277.
2. R. M. Murilla, G. G. Edilo, M. L. M. Budlayan, and E. S. Auxtero, “Boron delivery agents in BNCT: A mini review of current developments and emerging trends,” Nano TransMed, vol. 4, p. 100081, 2025, doi: https://doi.org/10.1016/j.ntm.2025.100081.
3. M. J. Akbar et al., “DFT investigation of iron-doped boron nitride nanoparticles for anastrozole drug delivery and molecular interaction,” Sci. Rep., vol. 15, no. 1, p. 8670, 2025.
4. A. I. Pastukhov et al., “Laser-ablative aqueous synthesis and characterization of elemental boron nanoparticles for biomedical applications,” Sci. Rep., vol. 12, no. 1, p. 9129, 2022.
5. A. B. Kakarla and I. Kong, “In Vitro and In Vivo Cytotoxicity of Boron Nitride Nanotubes: A Systematic Review.,” Nanomater. (Basel, Switzerland), vol. 12, no. 12, Jun. 2022, doi: 10.3390/nano12122069.
6. T. J. MacCormack et al., “Boron oxide nanoparticles exhibit minor, species-specific acute toxicity to north-temperate and amazonian freshwater fishes,” Front. Bioeng. Biotechnol., vol. 9, p. 689933, 2021.
7. D. Gonzalez-Ortiz, C. Salameh, M. Bechelany, and P. Miele, “Nanostructured boron nitride–based materials: synthesis and applications,” Mater. Today Adv., vol. 8, p. 100107, 2020, doi: https://doi.org/10.1016/j.mtadv.2020.100107.
8. A. O. Maselugbo, H. B. Harrison, and J. R. Alston, “Boron nitride nanotubes: a review of recent progress on purification methods and techniques,” J. Mater. Res., vol. 37, no. 24, pp. 4438–4458, 2022.

9. G. K. Wadhwa, D. J. Late, S. Charhate, and S. B. Sankhyan, “1D and 2D boron nitride nano structures: a critical analysis for emerging applications in the field of nanocomposites,” ACS omega, vol. 9, no. 25, pp. 26737–26761, 2024.
10. S. S. Hamd, A. Ramizy, and R. A. Ismail, “Preparation of novel B4C nanostructure/Si photodetectors by laser ablation in liquid,” Sci. Rep., vol. 12, no. 1, p. 16529, 2022.
11. Y. Chen et al., “Carboranes as unique pharmacophores in antitumor medicinal chemistry.,” Mol. Ther. oncolytics, vol. 24, pp. 400–416, Mar. 2022, doi: 10.1016/j.omto.2022.01.005.
12. S. D. Nehate, A. K. Saikumar, A. Prakash, and K. B. Sundaram, “A review of boron carbon nitride thin films and progress in nanomaterials,” Mater. Today Adv., vol. 8, p. 100106, 2020, doi: https://doi.org/10.1016/j.mtadv.2020.100106.
13. T. Ramachandran, H. Butt, L. Zheng, and M. Rezeq, “A review of 2D metal boride-derived nanostructures: From synthesis to energy storage and conversion applications,” J. Energy Storage, vol. 99, p. 113425, 2024, doi: https://doi.org/10.1016/j.est.2024.113425.
14. J. Liu, F. Zhang, X. Wang, F. Han, and Z. Yuan, “Numerical study on determining formation porosity using a boron capture gamma ray technique and MCNP,” Appl. Radiat. Isot., vol. 94, pp. 266–271, 2014.
15. K. O. Aiyyzhy, E. V Barmina, V. V Voronov, G. A. Shafeev, G. G. Novikov, and O. V Uvarov, “Laser ablation and fragmentation of Boron in liquids,” Opt. Laser Technol., vol. 155, p. 108393, 2022.
16. P. M. Revabhai, R. K. Singhal, H. Basu, and S. K. Kailasa, “Progress on boron nitride nanostructure materials: properties, synthesis and applications in hydrogen storage and analytical chemistry,” J. Nanostructure Chem., vol. 13, no. 1, pp. 1–41, 2023.
17. G. Darabdhara, P. Borthakur, P. K. Boruah, S. Sen, D. B. Pemmaraju, and M. R. Das, “Advancements in Two-Dimensional Boron Nitride Nanostructures: Properties, Preparation Methods, and their Biomedical Applications,” J. Mater. Chem. B, 2025.
18. I. N. Zavestovskaya et al., “Laser-synthesized elemental boron nanoparticles for efficient boron neutron capture therapy,” Int. J. Mol. Sci., vol. 24, no. 23, p. 17088, 2023.
19. M. Carlin et al., “Skin biocompatibility of hexagonal boron nitride: An in vitro study on HaCaT keratinocytes and 3D reconstructed human epidermis,” J. Hazard. Mater., vol. 494, p. 138449, 2025, doi: https://doi.org/10.1016/j.jhazmat.2025.138449.
20. S. Feng et al., “RBC membrane camouflaged boron nitride nanospheres for enhanced biocompatible performance,” Colloids Surfaces B Biointerfaces, vol. 190, p. 110964, 2020, doi: https://doi.org/10.1016/j.colsurfb.2020.110964.
21. G. K. Güven et al., “Boron-doped carbon quantum dots: A biocompatible nanoplatform for targeted cancer theranostics,” Int. J. Pharm., vol. 679, p. 125745, 2025, doi: https://doi.org/10.1016/j.ijpharm.2025.125745.
22. C. Wang et al., “Hexagonal boron nitride nanomaterials for biomedical applications,” BMEMat, vol. 2, no. 2, p. e12068, 2024.
23. D. Çetin Altındal, “Therapeutic potential of boron-based nanoparticles for enhanced glioblastoma treatment,” J. Drug Deliv. Sci. Technol., vol. 99, p. 105936, 2024, doi: https://doi.org/10.1016/j.jddst.2024.105936.
24. M. D’Amora, A. Camisasca, R. Arenal, and S. Giordani, “In vitro and in vivo biocompatibility of boron/nitrogen co-doped carbon nano-onions,” Nanomaterials, vol. 11, no. 11, p. 3017, 2021.
25. D. V Shtansky, A. T. Matveev, E. S. Permyakova, D. V Leybo, A. S. Konopatsky, and P. B. Sorokin, “Recent Progress in Fabrication and Application of BN Nanostructures and BN-Based Nanohybrids.,” Nanomater. (Basel, Switzerland), vol. 12, no. 16, Aug. 2022, doi: 10.3390/nano12162810.
26. V. S. Aigbodion, A. A. Alayyaf, and C. J. Ozoude, “Understanding the anti-corrosion characteristics of surface modification of h-BN and carbon nanotubes/magnesium composites in simulated seawater,” RSC Adv., vol. 14, no. 33, pp. 24152–24164, 2024.
27. S. Xu, Y. Yu, B. Zhang, K. Zhu, Y. Cheng, and T. Zhang, “Boron carbide nanoparticles for boron neutron capture therapy,” RSC Adv., vol. 15, no. 14, pp. 10717–10730, 2025.
28. K.-W. Lan et al., “In vivo investigation of boron-rich nanodrugs for treating triple-negative breast cancers via boron neutron capture therapy,” Biomater. Adv., vol. 155, p. 213699, 2023, doi: https://doi.org/10.1016/j.bioadv.2023.213699.
29. H. Li et al., “Biomimetic Boron Nitride Nanoparticles for Targeted Drug Delivery and Enhanced Antitumor Activity.,” Pharmaceutics, vol. 15, no. 4, Apr. 2023, doi: 10.3390/pharmaceutics15041269.
30. F. Abolhasani Zadeh et al., “Boron carbide nanotube as targeted drug delivery system for melphalan anticancer drug,” J. Mol. Liq., vol. 354, p. 118796, 2022, doi: https://doi.org/10.1016/j.molliq.2022.118796. [31] T. E. Gber et al., “Functionalized boron doped graphene (BGP) as smart nanocarrier for delivery of hydroxyurea (HU) drug,” Chem. Phys. Impact, vol. 7, p. 100291, 2023, doi: https://doi.org/10.1016/j.chphi.2023.100291.
31. A. Herrada Céspedes, M. Reyes, and J. O. Morales, “Advanced drug delivery systems for oral squamous cell carcinoma: A comprehensive review of nanotechnology-based and other innovative approaches,” Front. Drug Deliv., vol. 5, p. 1596964, 2025.
32. S. Feng, H. Zhang, C. Zhi, X.-D. Gao, and H. Nakanishi, “pH-responsive charge-reversal polymer-functionalized boron nitride nanospheres for intracellular doxorubicin delivery.,” Int. J. Nanomedicine, vol. 13, pp. 641–652, 2018, doi: 10.2147/IJN.S153476.
33. B. C. Das, P. Chokkalingam, P. Masilamani, S. Shukla, and S. Das, “Stimuli-responsive boron-based materials in drug delivery,” Int. J. Mol. Sci., vol. 24, no. 3, p. 2757, 2023.
34. X. Li, N. Hanagata, and D. Golberg, “Boron nitride nanomaterials for cancer therapy: Tailor-made strategies,” J. Mater. Res., pp. 1–17, 2025.
35. S. Feng, H. Zhang, S. Xu, C. Zhi, H. Nakanishi, and X.-D. Gao, “Folate-conjugated, mesoporous silica functionalized boron nitride nanospheres for targeted delivery of doxorubicin,” Mater. Sci. Eng. C, vol. 96, pp. 552–560, 2019, doi: https://doi.org/10.1016/j.msec.2018.11.063.
36. J. Ren, L. Stagi, and P. Innocenzi, “Hydroxylated boron nitride materials: from structures to functional applications,” J. Mater. Sci., vol. 56, no. 6, pp. 4053–4079, 2021.
37. W. Chai et al., “Recent progress in functional metal–organic frameworks for bio-medical application,” Regen. Biomater., vol. 11, p. rbad115, 2024.
38. M. Ahmadi, C. A. Ritter, T. von Woedtke, S. Bekeschus, and K. Wende, “Package delivered: folate receptor-mediated transporters in cancer therapy and diagnosis,” Chem. Sci., vol. 15, no. 6, pp. 1966–2006, 2024.
39. C. Li, L. Zhou, and X. Yin, “Pathophysiological aspects of transferrin-A potential nano-based drug delivery signaling molecule in therapeutic target for varied diseases,” Front. Pharmacol., vol. 15, p. 1342181, 2024.
40. F. Reeßing, S. E. M. Huijsse, R. A. J. O. Dierckx, B. L. Feringa, R. J. H. Borra, and W. Szymański, “A photocleavable contrast agent for light-responsive MRI,” Pharmaceuticals, vol. 13, no. 10, p. 296, 2020.
41. W. Zhang, H. Zhou, M. Ou, D. Sun, and C. Yang, “Luminescence and magnetic properties of bifunctional nanoparticles composited by nitrogen-doped graphene quantum dots and gadolinium,” J. Rare Earths, vol. 42, no. 4, pp. 716–723, 2024, doi: https://doi.org/10.1016/j.jre.2023.05.005.
42. M. A. Kouri et al., “Consolidation of gold and gadolinium nanoparticles: an extra step towards improving cancer imaging and therapy,” J. Nanotheranostics, vol. 4, no. 2, pp. 127–149, 2023.
43. W. Zhao, X. Yu, S. Peng, Y. Luo, J. Li, and L. Lu, “Construction of nanomaterials as contrast agents or probes for glioma imaging,” J. Nanobiotechnology, vol. 19, no. 1, p. 125, 2021.
44. F. Abi-Ghaida, S. Clément, A. Safa, D. Naoufal, and A. Mehdi, “Multifunctional Silica Nanoparticles Modified via Silylated‐Decaborate Precursors,” J. Nanomater., vol. 2015, no. 1, p. 608432, 2015.
45. T. D. Marforio, A. Carboni, and M. Calvaresi, “In Vivo Application of Carboranes for Boron Neutron Capture Therapy (BNCT): Structure, Formulation and Analytical Methods for Detection.,” Cancers (Basel)., vol. 15, no. 20, Oct. 2023, doi: 10.3390/cancers15204944.
46. X. Li, P. He, Y. Wei, C. Qu, F. Tang, and Y. Li, “Application and perspectives of nanomaterials in boron neutron capture therapy of tumors,” Cancer Nanotechnol., vol. 16, no. 1, p. 25, 2025.
47. J. Matović et al., “Towards New Delivery Agents for Boron Neutron Capture Therapy: Synthesis and In Vitro Evaluation of a Set of Fluorinated Carbohydrate Derivatives,” Molecules, vol. 29, no. 17, p. 4263, 2024.
48. G. Ailuno et al., “Boron vehiculating nanosystems for neutron capture therapy in cancer treatment,” Cells, vol. 11, no. 24, p. 4029, 2022.
49. E. Kar, Z. Övenler, C. Hacıoğlu, and F. Kar, “Boric Acid Induces Oxidative Damage and Apoptosis Through SEMA3A/PLXNA1/NRP1 Signalling Pathway in U251 Glioblastoma Cell,” J. Cell. Mol. Med., vol. 29, no. 9, p. e70578, 2025.
50. S. Kulkarni, D. Bhandary, Y. Singh, V. Monga, and S. Thareja, “Boron in cancer therapeutics: An overview,” Pharmacol. Ther., vol. 251, p. 108548, 2023, doi: https://doi.org/10.1016/j.pharmthera.2023.108548.
51. G. Paties Montagner, S. Dominici, S. Piaggi, A. Pompella, and A. Corti, “Redox Mechanisms Underlying the Cytostatic Effects of Boric Acid on Cancer Cells-An Issue Still Open.,” Antioxidants (Basel, Switzerland), vol. 12, no. 6, Jun. 2023, doi: 10.3390/antiox12061302.
52. X. Zhang, Y. Lin, N. S. Hosmane, and Y. Zhu, “Nanostructured boron agents for boron neutron capture therapy: a review of recent patents.,” Med. Rev., vol. 3, no. 5, pp. 425–443, Oct. 2023, doi: 10.1515/mr-2023-0013.
53. G. Cheng, H. Karoui, M. Hardy, and B. Kalyanaraman, “Polyphenolic Boronates Inhibit Tumor Cell Proliferation: Potential Mitigators of Oxidants in the Tumor Microenvironment,” Cancers (Basel)., vol. 15, no. 4, p. 1089, 2023.
54. T. Luo et al., “The dawn of a new era: tumor-targeting boron agents for neutron capture therapy,” Mol. Pharm., vol. 20, no. 10, pp. 4942–4970, 2023.
55. A. Monti Hughes and N. Hu, “Optimizing boron neutron capture therapy (BNCT) to treat cancer: an updated review on the latest developments on boron compounds and strategies,” Cancers (Basel)., vol. 15, no. 16, p. 4091, 2023.
56. A. Peat, “Novel Dyes for use as Boron Carriers in Boron Neutron Capture Therapy of Glioblastoma Multiforme,” 2023.
57. L. D. Punshon, M. R. Fabbrizi, B. Phoenix, S. Green, and J. L. Parsons, “Current insights into the radiobiology of boron neutron capture therapy and the potential for further improving biological effectiveness,” Cells, vol. 13, no. 24, p. 2065, 2024.
58. D. S. Seneviratne, O. Saifi, Y. Mackeyev, T. Malouff, and S. Krishnan, “Next-generation boron drugs and rational translational studies driving the revival of BNCT,” Cells, vol. 12, no. 10, p. 1398, 2023.
59. M. Martínez-Carmona, D. Lozano, M. Colilla, and M. Vallet-Regí, “Lectin-conjugated pH-responsive mesoporous silica nanoparticles for targeted bone cancer treatment,” Acta Biomater., vol. 65, pp. 393–404, 2018.
60. R. F. Barth, N. Gupta, and S. Kawabata, “Evaluation of sodium borocaptate (BSH) and boronophenylalanine (BPA) as boron delivery agents for neutron capture therapy (NCT) of cancer: an update and a guide for the future clinical evaluation of new boron delivery agents for NCT.,” Cancer Commun. (London, England), vol. 44, no. 8, pp. 893–909, Aug. 2024, doi: 10.1002/cac2.12582.
61. H. He et al., “The basis and advances in clinical application of boron neutron capture therapy,” Radiat. Oncol., vol. 16, no. 1, p. 216, 2021.
62. Q. Dai, Q. Yang, X. Bao, J. Chen, M. Han, and Q. Wei, “The development of boron analysis and imaging in boron neutron capture therapy (BNCT),” Mol. Pharm., vol. 19, no. 2, pp. 363–377, 2022.
63. A. G. Beck-Sickinger et al., “New Boron Delivery Agents.,” Cancer Biother. Radiopharm., vol. 38, no. 3, pp. 160–172, Apr. 2023, doi: 10.1089/cbr.2022.0060.
64. F. Ali, N. S Hosmane, and Y. Zhu, “Boron chemistry for medical applications,” Molecules, vol. 25, no. 4, p. 828, 2020.
65. S. M. Sharker, “Hexagonal boron nitrides (white graphene): a promising method for cancer drug delivery,” Int. J. Nanomedicine, pp. 9983–9993, 2019.
66. N. A. A. Ebrahim, S. M. A. Soliman, M. O. Othman, R. A. Salama, and N. S. Tahoun, “Nanotechnology in Neuro-Oncology: evaluating the potential of graphene and boron nitride nanostructures,” Biomed. Mater. Devices, pp. 1–11, 2025.
67. A. B. Fithroni et al., “Novel Drug Delivery Particles Can Provide Dual Effects on Cancer ‘Theranostics’ in Boron Neutron Capture Therapy,” Cells, vol. 14, no. 1, p. 60, 2025.
68. H. Xiong et al., “Doxorubicin-loaded carborane-conjugated polymeric nanoparticles as delivery system for combination cancer therapy,” Biomacromolecules, vol. 16, no. 12, pp. 3980–3988, 2015.
69. R. B. Mokhtari et al., “Combination therapy in combating cancer,” Oncotarget, vol. 8, no. 23, p. 38022, 2017.
70. B. Shrestha, L. Tang, and G. Romero, “Nanoparticles‐mediated combination therapies for cancer treatment,” Adv. Ther., vol. 2, no. 11, p. 1900076, 2019.
71. S. M. S. Mousavi-Kiasary et al., “Synergistic cancer therapies enhanced by nanoparticles: advancing Nanomedicine through multimodal strategies,” Pharmaceutics, vol. 17, no. 6, p. 682, 2025.
72. Y.-T. Zhou et al., “Recent progress of nano-drugs in neutron capture therapy,” Theranostics, vol. 14, no. 8, p. 3193, 2024.
73. J. Sforzi et al., “A novel pH sensitive theranostic PLGA nanoparticle for boron neutron capture therapy in mesothelioma treatment,” Sci. Rep., vol. 13, no. 1, p. 620, 2023.
74. W. A. G. Sauerwein et al., “Theranostics in boron neutron capture therapy,” Life, vol. 11, no. 4, p. 330, 2021.
75. Ö. I. Dikkatli and Ö. D. İseri, “Boron and beyond: Where do we stand in cancer treatment?,” J. Boron, vol. 8, no. 4, pp. 158–188, 2023.
76. S. Wang, Z. Zhang, L. Miao, and Y. Li, “Boron neutron capture therapy: current status and challenges,” Front. Oncol., vol. 12, p. 788770, 2022.
77. S. Shen et al., “A clinician’s perspective on boron neutron capture therapy: promising advances, ongoing trials, and future outlook,” Int. J. Radiat. Biol., vol. 100, no. 8, pp. 1126–1142, 2024.
78. L. Zhao, W. Yang, and Q. Lan, “Boron neutron capture therapy of cancer: Recent progress,” Med. Plus, vol. 1, no. 3, p. 100041, 2024, doi: https://doi.org/10.1016/j.medp.2024.100041.
79. X. Cheng, F. Li, and L. Liang, “Boron neutron capture therapy: clinical application and research progress,” Curr. Oncol., vol. 29, no. 10, pp. 7868–7886, 2022.
80. T. Zhou et al., “The current status and novel advances of boron neutron capture therapy clinical trials,” Am. J. Cancer Res., vol. 14, no. 2, p. 429, 2024. [82] T. D. Malouff et al., “Boron neutron capture therapy: a review of clinical applications,” Front. Oncol., vol. 11, p. 601820, 2021. [83] M. Shirakawa et al., “A novel boron lipid to modify liposomal surfaces for boron neutron capture therapy,” Cells, vol. 10, no. 12, p. 3421, 2021. [84] A. Balboni et al., “Human glioblastoma-derived cell membrane nanovesicles: A novel, cell-specific strategy for boron neutron capture therapy of brain tumors,” Sci. Rep., vol. 14, no. 1, p. 19225, 2024. [85] M. Shao et al., “Exosome membrane-coated nanosystems: Exploring biomedical applications in cancer diagnosis and therapy,” Matter, vol. 6, no. 3, pp. 761–799, 2023.