Bor içeren anti-kanser ilaç taşıyıcı nanoplatformlardaki güncel gelişmeler

Abstract

Bor içeren bileşikler, elektron eksikliği, geri dönüşümlü kovalent etkileşimler ve yapısal çeşitlilik gibi kendilerine özgü kimyasal özellikleri sayesinde gelişmiş antikanser ilaç taşıma sistemlerinin tasarımında çok yönlü yapı taşları olarak öne çıkmıştır. Son yıllarda, tümör hedeflemeyi artırmak, ilaç yükleme verimliliğini iyileştirmek ve sistemik toksisiteyi en aza indirirken kontrollü salım sağlamak amacıyla bor fonksiyonelleştirilmiş nanotaşıyıcıların mühendisliğinde önemli ilerlemeler kaydedilmiştir. Bu derleme, bor nitrür nanoparçacıkları, boronik asit fonksiyonelleştirilmiş polimerler, BODIPY tabanlı nanotaşıyıcılar ve bor içeren süpramoleküler nanoplatformlar dâhil olmak üzere bor içeren antikanser ilaç taşıma nanoplatformlarındaki son gelişmeleri özetlemektedir. Özellikle, tümör mikroçevresinde pH, ligand veya reaktif oksijen türleri ile tetiklenen ilaç salımı için boronik asitler ile cis-diol grupları arasındaki dinamik kovalent etkileşimlerden yararlanan uyarana duyarlı sistemlere odaklanılmaktadır. Hücresel alımı artırma, hücre içi stabiliteyi güçlendirme ve seçici sitotoksisite sağlama stratejileri de ele alınmaktadır. Ayrıca, görüntüleme yetenekleri veya kombinasyonel tedavi yaklaşımları içeren çok işlevli nanotaşıyıcılar incelenmektedir. Umut verici preklinik sonuçlara rağmen, büyük ölçekli üretim, uzun vadeli biyogüvenlik değerlendirmesi, farmakokinetik optimizasyon ve klinik uygulamaya geçiş konularında zorluklar devam etmektedir. Genel olarak, bor içeren nanotaşıyıcılar, hedefe yönelik ve uyarana duyarlı antikanser ilaç taşımayı ilerletme potansiyeli yüksek, hızla gelişen bir platformu temsil etmektedir.

Keywords

• Bor
• ilaç salımı
• nanoparçacık
• nanotaşıyıcı
• Antikanser
• Kanser terapisi

Recent advances in boron containing anticancer drug delivery nanocarrier platforms

Abstract

Boron-containing compounds have emerged as versatile building blocks in the design of advanced anticancer drug delivery systems due to their unique chemical features, including electron deficiency, reversible covalent interactions, and structural diversity. In recent years, significant progress has been made in engineering boron-functionalized nanocarriers to enhance tumor targeting, improve drug loading efficiency, and achieve controlled release while minimizing systemic toxicity. This review highlights recent advances in boron-containing anticancer drug delivery nanoplatforms, including boron-nitride nanoparticles, boronic acid-functionalized polymers, BODIPY-based nanocarriers and boron incorporated supramolecular nanoplatforms. Particular attention is given to stimulus-responsive systems exploiting the dynamic covalent interactions between boronic acids and cis-diols for pH-, ligand-, or reactive oxygen species-triggered drug release in the tumor microenvironment. Strategies to improve cellular uptake, enhance intracellular stability, and achieve selective cytotoxicity are also discussed. Furthermore, multifunctional nanocarriers incorporating imaging capabilities or combinatorial therapeutic modalities are examined. Despite promising preclinical results, challenges remain in large-scale production, long-term biosafety evaluation, pharmacokinetic optimization, and clinical translation. Overall, boron- containing nanocarriers represent a rapidly evolving platform with strong potential to advance targeted and responsive anticancer drug delivery.

Keywords

• Boron
• anticancer
• cancer therapy
• drug delivery
• nanocarrier
• nanoparticle.

References

1. Fink, H., Langselius, O., Vignat, J., Rumgay, H., Rehm, J., Martinez, R. X., … & Soerjomataram, I. (2026). Global and regional cancer burden attributable to modifiable risk factors to inform prevention. Nature Medicine, 32(4), 1306-1315. https://doi.org/10.1038/s41591-026-04219-7
2. Jung, Y., Longo, C., & Tompa, E. (2022). Longitudinal assessment of labor market earnings among patients diagnosed with cancer in Canada. JAMA Network Open, 5(12), e2245717-e2245717. https://doi.org/10.1001/JAMANETWORKOPEN.2022.45717
3. McKeague, B., & Maguire, R. (2021). “The effects of cancer on a family are way beyond the person who’s had it”: The experience and effect of a familial cancer diagnosis on the health behaviours of family members. European Journal of Oncology Nursing, 51, 101905. https://doi.org/10.1016/J.EJON.2021.101905
4. Zafar, A., Khatoon, S., Khan, M. J., Abu, J., & Naeem, A. (2025). Advancements and limitations in traditional anti-cancer therapies: A comprehensive review of surgery, chemotherapy, radiation therapy, and hormonal therapy. Discover Oncology, 16(1), 607. https://doi.org/10.1007/S12672-025-02198-8
5. Ezike, T. C., Okpala, U. S., Onoja, U. L., Nwike, C. P., Ezeako, E. C., Okpara, O. J., … & Nwanguma, B. C. (2023). Advances in drug delivery systems, challenges and future directions. Heliyon, 9(6), e17488. https://doi.org/10.1016/J.HELIYON.2023.E17488
6. Imtiaz, S., Ferdous, U. T., Nizela, A., Hasan, A., Shakoor, A., Zia, A. W., & Uddin, S. (2025). Mechanistic study of cancer drug delivery: Current techniques, limitations, and future prospects. European Journal of Medicinal Chemistry, 290, 117535. https://doi.org/10.1016/J.EJMECH.2025.117535
7. Zhang, X., Liu, W., Chu, H., & Zong, W. (2026). Liposomes: A breakthrough in advanced drug delivery systems. Advances in Colloid and Interface Science, 353, 103887. https://doi.org/10.1016/J.CIS.2026.103887
8. Papavasileiou, E. Z., Rekkas, D. M., Dallas, P. P., Pispas, S., & Pippa, N. (2026). Unlocking the potential of micelles: DoE and QbD strategies for formulation development and optimization. Journal of Drug Delivery Science and Technology, 115, 107795. https://doi.org/10.1016/J.JDDST.2025.107795

9. Hussein, H. A., Khaphi, F. L., Sivaramakrishnan, R., Poornima, S., & Abdullah, M. A. (2025). Recent developments in sustained-release and targeted drug delivery applications of solid lipid nanoparticles. Journal of Microencapsulation, 42(5), 472-502. https://doi.org/10.1080/02652048.2025.2495290
10. Arif, Y., Sameeya, Hasan, N., Gowda, B. H. J., Gupta, G., Alsayari, A., … & Kesharwani, P. (2024). Advancements in dendrimer-based drug delivery for combinatorial cancer therapy. Journal of Drug Delivery Science and Technology, 97, 105755. https://doi.org/10.1016/J.JDDST.2024.105755
11. Waghmare, P., Shafi, S., Swami, S., Gadhave, A., Damane, M., & Syed, S. M. (2026). Sponging innovations: A new era of porous nanocarriers in drug delivery and biomedical applications. Current Pharmaceutical Analysis, 22(2), 181-195. https://doi.org/10.1016/J.CPAN.2025.12.011
12. Jiang, F., Li, J., Yang, S., Zou, P., Liu, W., Liu, J., … & Pan, Y. (2025). Perspectives and challenges on metal-organic framework-based porous materials in therapies targeting of gastrointestinal tract. Chemical Engineering Journal, 519, 164946. https://doi.org/10.1016/J.CEJ.2025.164946
13. Iannazzo, D., Celesti, C., Cardo, L., Prato, M., & Bitto, A. (2026). Carbon dots for drug delivery: Insights into their potential in nanopharmacology. Pharmacological Reviews, 78(2), 100107. https://doi.org/10.1016/J.PHARMR.2025.100107
14. Alsuraifi, A., Mouzan, M. M., Algzaare, A., Aqeel, Z., Al- Essa, U. I., Noor, N. A., & Ayad, A. (2025). Quantum dots: Catalysts for a new era of precision medicine and biomedical innovation. Journal of Fluorescence, 36(1), 257-320. https://doi.org/10.1007/S10895-025-04452-2
15. Li, C., Ma, Z., Sun, X., Li, J., Liang, J., Wang, F., … & Cui, W. (2026). Activation of bone tumor-eating macrophages via assembling and co-delivering 3D printed scaffold. Biomaterials, 324(22), 123495. https://doi.org/10.1016/j.biomaterials.2025.123495
16. Güven, G. K., Okur, M. E., Ayla, Ş., Çalışkan, G., Al, M. N., Gülüm, L., … & Değim, İ. T. (2025). Boron-doped carbon quantum dots: A biocompatible nanoplatform for targeted cancer theranostics. International Journal of Pharmaceutics, 679(10), 125745. https://doi.org/10.1016/j.ijpharm.2025.125745
17. Raj, P., Gadewar, M. M., Krishna, P. G., Paramanick, D., Rao, S., Shankaraiah, L. H., & Bhagya, N. P. (2026). Enhanced targeted delivery of cisplatin via folate and boron-modified magnetic nanoparticles: A promising approach for cervical cancer treatment. Next Nanotechnology, 9(11), 100352. https://doi.org/10.1016/j.nxnano.2025.100352
18. Cicek, N., Cobandede, Z., Adiguzel, S., Yilmaz, H., & Culha, M. (2025). Synergistic anti-cancer effects of piezoelectric hexagonal boron nitride nanocarriers for controlled doxorubicin release. Nanomedicine, 20(5), 455-466. https://doi.org/10.1080/17435889.2025.2459 055
19. Radan, M., Carev, I., Miloš, M., & Bakić, M. T. (2025). Phenylboronic acid in targeted cancer therapy and diagnosis. Theranostics, 15(9), 3733-3748. https://doi.org/10.7150/THNO.104558
20. Darabdhara, G., Borthakur, P., Boruah, P. K., Sen, S., Pemmaraju, D. B., & Das, M. R. (2025). Advancements in two-dimensional boron nitride nanostructures: Properties, preparation methods, and their biomedical applications. Journal of Materials Chemistry B, 13(37), 11540-11581. https://doi.org/10.1039/D5TB00469A
21. Zheng, D., Han, G., Lemus, O. D. M., Podgorsak, A., Webster, M., Li, F., … & Yoon, J. (2026). Boron neutron capture therapy: A technology-driven renaissance. Cancers, 18(3), 498. https://doi.org/10.3390/CANCERS18030498
22. Yang, R., Shi, M., Zhang, Y., Ma, H., Chen, X., & Xu, X. (2026). Achievements, challenges, and perspectives in the design of boron delivery agents for neutron capture therapy. Coordination Chemistry Reviews, 553, 217555. https://doi.org/10.1016/J.CCR.2025.217555
23. Duo, Y., Xie, Z., Wang, L., Mahmood Abbasi, N., Yang, T., Li, Z., … & Zhang, H. (2021). Borophene-based biomedical applications: Status and future challenges. Coordination Chemistry Reviews, 427, 213549. https://doi.org/10.1016/J.CCR.2020.213549
24. Sohrabi, H., Arbabzadeh, O., Falaki, M., Vatanpour, V., Majidi, M. R., Kudaibergenov, N., … & Khataee, A. (2023). Advances in fabrication, physio-chemical properties, and sensing applications of non-metal boron nitride and boron carbon nitride-based nanomaterials. Surfaces and Interfaces, 41, 103152. https://doi.org/10.1016/j.surfin.2023.103152
25. Das, B. C., Chokkalingam, P., Masilamani, P., Shukla, S., & Das, S. (2023). Stimuli-responsive boron-based materials in drug delivery. International Journal of Molecular Sciences, 24(3), 2757. https://doi.org/10.3390/ijms24032757
26. Hayat, A., Sohail, M., Hamdy, M. S., Taha, T. A., AlSalem, H. S., Alenad, A. M., … & Mane, S. K. B. (2022). Fabrication, characteristics, and applications of boron nitride and their composite nanomaterials. Surfaces and Interfaces, 29, 101725. https://doi.org/10.1016/J.SURFIN.2022.101725
27. Tay, R. Y., Li, H., Wang, H., Lin, J., Ng, Z. K., Shivakumar, R., … & Teo, E. H. T. (2023). Advanced nano boron nitride architectures: Synthesis, properties and emerging applications. Nano Today, 53, 102011. https://doi.org/10.1016/J.NANTOD.2023.102011
28. Yang, D., Dai, P., Jiang, X., Alshehri, S. M., Ahamad, T., Bando, Y., & Wang, X. (2024). Methods for preparation of hexagonal boron nitride nanomaterials. Chemistry of Materials, 36(20), 10008-10053. https://doi.org/10.1021/ACS.CHEMMATER.4C00582
29. Arivazhagan, P., Usharani, N. J., Raju, M. J. S., & Bhattacharya, S. S. (2023). Studies on drug carrier potential of spherical boron nitride nanoparticles in cancer therapy. Journal of Materials Science, 58(19), 8076-8091. https://doi.org/10.1007/s10853-023-08543-y
30. Grams, R. J., Santos, W. L., Scorei, I. R., Abad-García, A., Rosenblum, C. A., Bita, A., … & Soriano-Ursúa, M. A. (2024). The Rise of boron-containing compounds: Advancements in synthesis, medicinal chemistry, and emerging pharmacology. Chemical Reviews, 124(5), 2441-2511. https://doi.org/10.1021/ACS.CHEMREV.3C00663
31. Sun, W., Zhao, X., Fan, J., Du, J., & Peng, X. (2019). Boron dipyrromethene nano-photosensitizers for anticancer phototherapies. Small, 15(32), https://doi.org/10.1002/smll.201804927
32. Wang, J., Gong, Q., Jiao, L., & Hao, E. (2023). Research advances in BODIPY-assembled supramolecular photosensitizers for photodynamic therapy. Coordination Chemistry Reviews, 496, 215367. https://doi.org/10.1016/J.CCR.2023.215367
33. Mao, Z., Kim, J. H., Lee, J., Xiong, H., Zhang, F., & Kim, J. S. (2023). Engineering of BODIPY-based theranostics for cancer therapy. Coordination Chemistry Reviews, 476, 214908. https://doi.org/10.1016/J.CCR.2022.214908
34. Noel, K. J., Umashankar, M. S., & Narayanasamy, D. (2024). Exploring research on the drug loading capacity of quantum dots. Cureus, 16(8), e67869. https://doi.org/10.7759/CUREUS.67869
35. Badıllı, U., Mollarasouli, F., Bakirhan, N. K., Ozkan, Y., & Ozkan, S. A. (2020). Role of quantum dots in pharmaceutical and biomedical analysis, and its application in drug delivery. TrAC Trends in Analytical Chemistry, 131, 116013. https://doi.org/10.1016/J.TRAC.2020.116013
36. Carrera Espinoza, M. J., Lin, K.-S., Weng, M.-T., Kunene, S. C., Lin, Y.-S., & Liu, S.-Y. (2023). Magnetic boron nitride nanosheets-based on pH-responsive smart nanocarriers for the delivery of doxorubicin for liver cancer treatment. Colloids and Surfaces B: Biointerfaces, 222, 113129. https://doi.org/10.1016/j.colsurfb.2023.113129
37. Emanet, M., Şen, Ö., & Çulha, M. (2017). Evaluation of boron nitride nanotubes and hexagonal boron nitrides as nanocarriers for cancer drugs. Nanomedicine, 12(7), 797-810. https://doi.org/10.2217/NNM-2016-0322
38. Zhou, S., Dai, L., Pan, L., Shen, G., & Qian, Z. (2025). Phenylboronic acid-modified nanoparticles for cancer treatment. Chemical Communications, 61(24), 4595- 4605. https://doi.org/10.1039/D4CC06730D
39. Nair, R. R., Råberg, L., Mårtensson, H., Jia, F., Gu, Y., Yakubu, H., … & Stubelius, A. (2026). Advances in phenylboronic acid and phenylboronic ester-based responsive systems for precision medicine. Biomaterials Science, 14(3), 661-683. https://doi.org/10.1039/D5BM01624J
40. Hassan, E. M., McWhirter, S., Walker, G. C., Martinez- Rubi, Y., & Zou, S. (2023). Elimination of cancer cells in co-culture: role of different nanocarriers in regulation of CD47 and calreticulin-induced phagocytosis. ACS Applied Materials & Interfaces, 15(3), 3791-3803. https://doi.org/10.1021/acsami.2c19311
41. Martinez-Rubi, Y., Jakubek, Z. J., Jakubinek, M. B., Kim, K. S., Cheng, F., Couillard, M., … & Simard, B. (2015). Self-assembly and visualization of poly(3- hexyl-thiophene) chain alignment along boron nitride nanotubes. The Journal of Physical Chemistry C, 119(47), 26605-26610. https://doi.org/10.1021/acs.jpcc.5b09049
42. Augustine, J., Cheung, T., Gies, V., Boughton, J., Chen, M., Jakubek, Z. J., … & Zou, S. (2019). Assessing size-dependent cytotoxicity of boron nitride nanotubes using a novel cardiomyocyte AFM assay. Nanoscale Advances, 1(5), 1914-1923. https://doi.org/10.1039/C9NA00104B
43. Del Turco, S., Ciofani, G., Cappello, V., Gemmi, M., Cervelli, T., Saponaro, C., … & Mattoli, V. (2013). Cytocompatibility evaluation of glycol-chitosan coated boron nitride nanotubes in human endothelial cells. Colloids and Surfaces B: Biointerfaces, 111, 142-149. https://doi.org/10.1016/J.COLSURFB.2013.05.031
44. Raffa, V., Ciofani, G., & Cuschieri, A. (2009). Enhanced low voltage cell electropermeabilization by boron nitride nanotubes. Nanotechnology, 20(7), 075104. https://doi.org/10.1088/0957-4484/20/7/075104
45. Asif, K., Rahman, Md. M., Sfriso, A. A., Parisi, S., Canzonieri, V., Caligiuri, I., … & Adeel, M. (2024). Biodegradation of hydroxylated boron nitride nanoplatelets, their toxic effect and drug delivery application. RSC Advances, 14(36), 26568-26579. https://doi.org/10.1039/D4RA04433A
46. Lv, J., Yang, Z., Wang, C., Duan, J., Ren, L., Rong, G., … & Cheng, Y. (2023). Efficient intracellular and in vivo delivery of toxin proteins by a ROS-responsive polymer for cancer therapy. Journal of Controlled Release, 355(4), 160-170. https://doi.org/10.1016/j.jconrel.2023.01.064
47. Otremba, T., & Ravoo, B. J. (2017). Dynamic multivalent interaction of phenylboronic acid functionalized dendrimers with vesicles. Tetrahedron, 73(33), 4972- 4978. https://doi.org/10.1016/J.TET.2017.04.043
48. Wang, X.-S., Zheng, Z.-S., Zheng, M.-F., Wang, D., Zhang, H.-L., Zhang, Z.-Q., … & Han, X.-M. (2023). IL- 2-loaded polypeptide nanoparticles for enhanced anti-cancer immunotherapy. Chinese Journal of Polymer Science, 41(7), 1059-1068. https://doi.org/10.1007/s10118-023-2898-2
49. Wang, Z., Cheng, H., Sheng, Y., Chen, Z., Zhu, X., Ren, J., … & Ding, Y. (2022). Biofunctionalized graphene oxide nanosheet for amplifying antitumor therapy: Multimodal high drug encapsulation, prolonged hyperthermal window, and deep-site burst drug release. Biomaterials, 287(11), 121629. https://doi. org/10.1016/j.biomaterials.2022.121629
50. Yang, Q., Wang, R., Lingling, H., Bian, Q., & Wei, Q. (2026). Nanobiomaterial-enabled boron delivery systems and innovative strategies for revolutionizing BNCT. Theranostics, 16(9), 4702-4725. https://doi.org/10.7150/THNO.126209
51. Xu, Y., Chen, X., Zhang, L., Li, P., He, J., Zhu, M., … & Jin, X. (2025). Boron phenylalanine-modified polydopamine nanoparticles for targeted delivery of danusertib in non-small cell lung cancer. International Journal of Nanomedicine, 20, 8415-8432. https://doi.org/10.2147/IJN.S519608
52. Yan, Y., Zhou, L., Sun, Z., Song, D., & Cheng, Y. (2022). Targeted and intracellular delivery of protein therapeutics by a boronated polymer for the treatment of bone tumors. Bioactive Materials, 7(4), 333-340. https://doi.org/10.1016/j.bioactmat.2021.05.041
53. Jasim, S. A., Al-Lami, M. S., Ameer, A. J., Shather, A. H., Aldhalmi, A. K., Taki, A. G., … & Saraswat, S. K. (2024). Nanostructures of boron nitride: A promising nanocarrier for anti-cancer drug delivery. Micro and Nanostructures, 185(8), 207708. https://doi.org/10.1016/j.micrna.2023.207708
54. Hassan, E. M., Walker, G. C., Wang, C., & Zou, S. (2020). Anti-leukemia effect associated with down-regulated CD47 and up-regulated calreticulin by stimulated macrophages in co-culture. Cancer Immunology, Immunotherapy, 70(3), 787-801. https:// doi.org/10.1007/s00262-020-02728-z
55. Tabanelli, R., Brogi, S., & Calderone, V. (2021). Improving curcumin bioavailability: Current strategies and future perspectives. Pharmaceutics, 13(10). https://doi.org/10.3390/pharmaceutics13101715
56. Şen, Ö., Emanet, M., Mazzuferi, M., Bartolucci, M., Catalano, F., Prato, M., … & Ciofani, G. (2023). Microglia polarization and antiglioma effects fostered by dual cell membrane-coated doxorubicin-loaded hexagonal boron nitride nanoflakes. ACS Applied Materials & Interfaces, 15(50), 58260-58273. https://doi.org/10.1021/acsami.3c17097
57. Feng, Z., Qi, Y., Liu, Q., Wang, X., Wang, Y., Wang, J., & Chen, X. (2026). Synergetic photoimmunotherapy with dual-inhibition of EZH2/Akt. New Journal of Chemistry. https://doi.org/10.1039/D5NJ04814A
58. Fu, Q., Sun, S., Lu, K., Li, N., & Dong, Z. (2024). Boron-doped carbon dots: Doping strategies, performance effects, and applications. Chinese Chemical Letters, 35(7), 109136. https://doi.org/10.1016/J.CCLET.2023.109136
59. Zhang, X., Wu, M., Hou, A., Xie, K., Li, F., & Gao, A. (2024). Boron-doped carbon quantum dot/carbon nanorod/graphitic carbon nitride composites for photocatalytic degradation of organic pollutants. ACS Applied Nano Materials, 7(11), 13501-13511. https://doi.org/10.1021/acsanm.4c01800
60. Das, R. K., & Mohapatra, S. (2017). Highly luminescent, heteroatom-doped carbon quantum dots for ultrasensitive sensing of glucosamine and targeted imaging of liver cancer cells. Journal of Materials Chemistry B, 5(11), 2190-2197. https://doi.org/10.1039/C6TB03141B
61. Alibolandi, Z., Seyed Hosseini, E., Mirsafi, A., Pourhanifeh, M. H., Jafari, S. M., Yasamian, A., … & Masoum, S. (2025). Molecular insights into paclitaxel and curcumin-loaded carbon dots: Computational and experimental evidence of NRF2 and autophagy modulation in ovarian cancer. ACS Applied Bio Materials, 8(10), 8673-8686. https://doi.org/10.1021/acsabm.5c00701
62. Turksoy, A., Yildiz, D., & Akkaya, E. U. (2019). Photosensitization and controlled photosensitization with BODIPY dyes. Coordination Chemistry Reviews, 379(3), 47-64. https://doi.org/10.1016/j.ccr.2017.09.029
63. Schad, C., Ray, C., Díaz-Norambuena, C., Serrano- Buitrago, S., Moreno, F., Maroto, B. L., … & Moya, S. de la. (2025). Water-soluble BODIPY dyes: A novel approach for their sustainable chemistry and applied photonics. Chemical Science, 16(18), 8030-8039. https://doi.org/10.1039/d5sc01295c
64. Wang, H., Zhang, Y., & Zhou, M. (2026). Molecularly engineered BODIPY photosensitizers for combined cancer phototherapy and immunotherapy. Frontiers in Pharmacology, 17, 1849977. https://doi.org/10.3389/fphar.2026.1849977
65. Zhang, J., Jiang, M., Li, Y., Yu, J., Qiu, H., Gu, M., … & Yin, S. (2022). Self-assembled boron dipyrromethene-based nanocarriers with encapsulated doxorubicin for chemo-photodynamic therapy. Dyes and Pigments, 206(1), 110679. https://doi.org/10.1016/j.dyepig.2022.110679
66. Li, H., Fan, Y., Shen, Y., Xu, H., Zhang, H., Chen, F., & Feng, S. (2024). Acid-activated TAT peptide-modified biomimetic boron nitride nanoparticles for enhanced targeted codelivery of doxorubicin and indocyanine green: A synergistic cancer photothermal and chemotherapeutic approach. ACS Applied Materials & Interfaces, 16(19), 25101-25112. https://doi.org/10.1021/acsami.4c01622
67. García-Fernández, J., & Fuente Freire, M. de la. (2023). Exosome-like systems: Nanotechnology to overcome challenges for targeted cancer therapies. Cancer Letters, 561(3), 216151. https://doi.org/10.1016/j.canlet.2023.216151
68. Palakurthi, S. S., Shah, B., Kapre, S., Charbe, N., Immanuel, S., Pasham, S., … & Palakurthi, S. (2024). A comprehensive review of challenges and advances in exosome-based drug delivery systems. Nanoscale Advances, 6(23), 5803-5826. https://doi.org/10.1039/d4na00501e
69. Zhang, Y.-X., Wang, M., Xu, L.-L., Chen, Y.-J., Zhong, S.-T., Feng, Y., … & Huang, W.-H. (2025). An integrated microfluidic chip for synchronous drug loading, separation and detection of plasma exosomes. Lab on a Chip, 25(13), 3185-3196. https://doi.org/10.1039/D5LC00279F
70. Sun, C., Ma, F., Cai, L., Wang, A., Wu, Y., Zhao, M., … & Hao, X. (2017). Metal-free ternary bcn nanosheets with synergetic effect of band gap engineering and magnetic properties. Scientific Reports, 7(1), 6617. https://doi.org/10.1038/s41598-017-07143-6
71. Yang, H., Li, J., Gu, S., Wu, Z., Luo, L., & Chen, Y. (2022). Fabrication of hexagonal boron carbonitride nanoplates using for in vitro photodynamic therapy and chemo therapy. Colloids and Surfaces B: Biointerfaces, 212(13), 112377. https://doi.org/10.1016/j.colsurfb.2022.112377
72. Wang, H., Wang, C., Deng, Y., Han, Y., Xiang, S., Xiao, H., & Weng, Q. (2023). Flower-like porous BCN assembled by nanosheets for paclitaxel delivery. Chemical Communications, 59(80), 11995-11998. https://doi.org/10.1039/D3CC03320A
73. Yadav, S., Sadique, Mohd. A., Kaushik, A., Ranjan, P., Khan, R., & Srivastava, A. K. (2022). Borophene as an emerging 2D flatland for biomedical applications: Current challenges and future prospects. Journal of Materials Chemistry B, 10(8), 1146-1175. https://doi.org/10.1039/D1TB02277F
74. Fu, Z., Williams, G. R., Niu, S., Wu, J., Gao, F., Zhang, X., … & Zhu, L.-M. (2020). Functionalized boron nanosheets as an intelligent nanoplatform for synergistic low-temperature photothermal therapy and chemotherapy. Nanoscale, 12(27), 14739-14750. https://doi.org/10.1039/D0NR02291H
75. Zhao, Y., Liu, N., Liu, P., Fan, T., Ma, R., Hong, H., … & Chen, T. (2022). Robust boron nanoplatform provokes potent tumoricidal activities via inhibiting heat shock protein. Asian Journal of Pharmaceutical Sciences, 17(5), 728-740. https://doi.org/10.1016/j.ajps.2022.06.003
76. Ji, X., Kong, N., Wang, J., Li, W., Xiao, Y., Gan, S. T., … & Shi, J. (2018). A Novel Top-own Synthesis of Ultrathin 2D Boron Nanosheets for Multimodal Imaging-Guided Cancer Therapy. Advanced Materials, 30(36), 1803031. https://doi.org/10.1002/adma.201803031
77. Elbeltagi, S., Mansour, S., Alanazi, M. A., El-Reash, Y. G. A., El-Yazeed, W. S. A., Al-Theyab, N. S., & Eldin, Z. E. (2026). Development and evaluation of exosome-encapsulated lenvatinib/h-BN nanocomposites for targeted chemo-photothermal therapy of hepatocellular carcinoma with enhanced pharmacokinetics. Journal of Molecular Structure, 1354(10), 144867. https://doi.org/10.1016/j.molstruc.2025.144867
78. Xu, H.-Z., Li, T.-F., Ma, Y., Li, K., Zhang, Q., Xu, Y.-H., … & Chen, X. (2022). Targeted photodynamic therapy of glioblastoma mediated by platelets with photo-controlled release property. Biomaterials, 290, 121833. https://doi. org/10.1016/j.biomaterials.2022.121833
79. Xie, X., Zhang, S., Liu, M., Ye, Y., Huang, Y., Li, Z., … & Tu, Z. (2025). Boosting anti-tumor immunity with boron-based nanosheets via photodynamic-elicited pyroptosis and adjuvant delivery. Journal of Materials Chemistry B, 13(28), 8380-8394. https://doi.org/10.1039/D5TB00801H
80. Long, K., Lv, W., Wang, Z., Zhang, Y., Chen, K., Fan, N., … & Wang, W. (2023). Near-infrared light-triggered prodrug photolysis by one-step energy transfer. Nature Communications, 14(1), 8112. https://doi.org/10.1038/s41467-023-43805-y
81. Zeng, L., Jiang, L., Li, J., Huang, L., Chen, Y., Yu, N., … & Han, G. (2023). Metal-free far-red light-driven photolysis via triplet fusion to enhance checkpoint blockade immunotherapy. Angewandte Chemie International Edition, 62(11), e202218341. https://doi.org/10.1002/anie.202218341
82. Wu, D., Zhang, Z., Li, X., Zhou, J., Cao, Y., Qi, S., … & Yu, G. (2023). Dynamically assembled nanomedicine based on host-guest molecular recognition for NIR laser-excited chemotherapy and phototheranostics. Acta Biomaterialia, 168(8), 565-579. https://doi.org/10.1016/j.actbio.2023.07.022
83. Long, K., Wang, Y., Lv, W., Yang, Y., Xu, S., Zhan, C., & Wang, W. (2022). Photoresponsive prodrug-dye nanoassembly for in-situ monitorable cancer therapy. Bioengineering & Translational Medicine, 7(3), e10311. https://doi.org/10.1002/btm2.10311
84. Liberti, M. V., & Locasale, J. W. (2016). The Warburg effect: How does it benefit cancer cells? Trends in Biochemical Sciences, 41(3), 211. https://doi. org/10.1016/j.tibs.2015.12.001
85. Su, J., Yan, T., Zhang, X., Yan, T., & Wang, Z. (2025). Tumor microenvironment-responsive diagnosis and treatment of integrated drug-loaded CdTe quantum dots for treatment tumors. Nanotechnology, 36(23), 235101. https://doi.org/10.1088/1361-6528/add6ad
86. Mohan, H., Salaroglio, I. C., Bartkowski, M., Courtney, K., Andreana, I., Limongi, T., … & Giordani, S. (2025). B/N-doped carbon nano-onions as nanocarriers for targeted breast cancer therapy. Nanoscale, 17(19), 12108-12123. https://doi.org/10.1039/D4NR04990J
87. Li, H., Qiao, W., Shen, Y., Xu, H., Fan, Y., Liu, Y., … & Feng, S. (2023). Biomimetic boron nitride nanoparticles for targeted drug delivery and enhanced antitumor activity. Pharmaceutics, 15(4), 1269. https://doi.org/10.3390/pharmaceutics15041269
88. Zhu, J., Guo, T., Wang, Z., & Zhao, Y. (2022). Triggered azobenzene-based prodrugs and drug delivery systems. Journal of Controlled Release, 345(15), 475- 493. https://doi.org/10.1016/j.jconrel.2022.03.041
89. Li, X., Sun, X., Wang, Y., Chen, H., & Gao, Y. (2025). A nanotheranostics with hypoxia-switchable fluorescence and photothermal effect for hypoxia imaging-guided immunosuppressive tumor microenvironment modulation. Journal of Colloid and Interface Science, 678(2), 897-912. https://doi.org/10.1016/j.jcis.2024.09.133
90. Yang, D.-C., Yang, X.-Z., Luo, C.-M., Wen, L.-F., Liu, J.- Y., & Lin, Z. (2022). A promising strategy for synergistic cancer therapy by integrating a photosensitizer into a hypoxia-activated prodrug. European Journal of Medicinal Chemistry, 243(42), 114749. https://doi.org/10.1016/j.ejmech.2022.114749
91. Nakamura, H., & Takada, K. (2021). Reactive oxygen species in cancer: Current findings and future directions. Cancer Science, 112(10), 3945. https://doi.org/10.1111/CAS.15068
92. Zhou, J., Li, K., Zang, X., Xie, Y., Song, J., & Chen, X. (2023). ROS-responsive galactosylated-nanoparticles with doxorubicin entrapment for triple negative breast cancer therapy. International Journal of Nanomedicine, 18, 1381-1397. https://doi.org/10.2147/IJN.S396087
93. Lyu, Z., Liu, W., & Chen, C. (2025). Harnessing piezoelectric materials for tumor therapy: Current advances and outlook. Acta Biomaterialia, 202, 66-84. https://doi.org/10.1016/J.ACTBIO.2025.06.058
94. Huang, X., Qu, F., Ma, Y., & Lin, H. (2025). Homologous boron nitride heterostructure: Piezoelectricity, catalysis, and nitric oxide release to reprogram the tumor microenvironment for anticancer. ACS Applied Materials & Interfaces, 17(21), 30700-30715. https://doi.org/10.1021/ACSAMI.5C04807
95. Ding, Y., Dai, Y., Wu, M., & Li, L. (2021). Glutathione-mediated nanomedicines for cancer diagnosis and therapy. Chemical Engineering Journal, 426, 128880. https://doi.org/10.1016/J.CEJ.2021.128880
96. Behera, P., Karunakaran, S., Sahoo, J., Bhatt, P., Rana, S., & De, M. (2023). Ligand exchange on MoS2 nanosheets: Applications in array-based sensing and drug delivery. ACS Nano, 17(2), 1000-1011. https://doi.org/10.1021/acsnano.2c06994
97. Tang, J., Shi, J., & Liu, J. (2023). Editorial: Advances in 3D cell culture for drug screening and toxicology evaluation. Frontiers in Bioengineering and Biotechnology, 11, 1266506. https://doi.org/10.3389/FBIOE.2023.1266506
98. Venugopal Menon, N., Lee, J., Tang, T., & Lim, C. T. (2025). Microfluidics for morpholomics and spatial omics applications. Lab on a Chip, 25(5), 752-763. https://doi.org/10.1039/D4LC00869C
99. Emanet Ciofani, M., Şen, Ö., & Çulha, M. (2020). Hexagonal boron nitride nanoparticles for prostate cancer treatment. ACS Applied Nano Materials, 3(3), 2364-2372. https://doi.org/10.1021/ACSANM.9B02486
100. Maharjan, S., Gautam, M., Poudel, K., Yong, C. S., Ku, S. K., Kim, J. O., & Byeon, J. H. (2022). Streamlined plug-in aerosol prototype for reconfigurable manufacture of nano-drug delivery systems. Biomaterials, 284(10), 121511. https://doi. org/10.1016/j.biomaterials.2022.121511
101. Center for Drug Evaluation and Research (2022). Drug products, including biological products, that contain nanomaterials - Guidance for industry (FDA- 2017-D-0759). Food and Drug Administration. https://www.fda.gov/media/157812/download
102. Committee for Medicinal Products for Human Use. (2013). Reflection paper on surface coatings: General issues for consideration regarding parenteral administration of coated nanomedicine products (EMA/325027/2013). European Medicines Agency. https://www.ema.europa.eu/en/documents/scientific-guideline/reflection-paper-surface-coatings-general-issues-consideration-regarding-parenteral-administration-coated-nanomedicine-products_en.pdf
103. European Medicines Agency. (2013). ICH S9 Non-clinical evaluation for anticancer pharmaceuticals - Scientific guideline (EMA/CHMP/ICH/646107/2008). European Medicines Agency. https://www.ema.europa.eu/en/documents/scientific-guideline/ich-guideline-s9-non-clinical-evaluation-anticancer-pharmaceuticals-step-5_en.pdf
104. Jia, J., Wu, G., Zhang, H., Wang, F., Gu, X., Dorma, D., … & Xie, H. (2025). Magnetic-driven hydrogel robots loaded with mitomycin for active therapy of bladder cancer. ACS Applied Materials & Interfaces, 17(25), 36366-36376. https://doi.org/10.1021/acsami.5c03787
105. Yang, D.-C., Wen, L.-F., Du, L., Luo, C.-M., Lu, Z.-Y., Liu, J.-Y., & Lin, Z. (2022). A hypoxia-activated prodrug conjugated with a BODIPY-based photothermal agent for imaging-guided chemo-photothermal combination therapy. ACS Applied Materials & Interfaces, 14(36), 40546-40558. https://doi.org/10.1021/acsami.2c09071