Engineering Smart Nanoparticles to Simultaneously Trigger Apoptosis, Ferroptosis, and Pyroptosis in Resistant Tumors
Keywords:
Smart nanoparticles, Apoptosis, Ferroptosis, Pyroptosis, Therapy-resistant tumors, Multimodal programmed cell death, Reactive oxygen species, Immunogenic cell death.Abstract
Despite advancements in targeted medicines and immunotherapies, cancer resistance continues to be a major problem in oncology, resulting in poor clinical results. Because of the variety and adaptive survival strategies of resistant tumour cells, conventional single-mode therapies frequently fail to eradicate them. Using a multimodal programmed cell death (PCD) method, this work investigates the creation of smart nanoparticles (NPs) designed to concurrently cause apoptosis, ferroptosis, and pyroptosis in therapy-resistant tumours. Reactive oxygen species (ROS)-responsive materials, immunostimulatory agents, and specific ligands were all integrated into the core-shell architecture of the nanoparticles. Ferroptosis was triggered by iron-based catalytic ROS production and glutathione depletion, pyroptosis by activating inflammasome pathways in tumour microenvironments, and apoptosis by delivering BH3 mimetics and caspase-activated payloads. With notable ROS generation, lipid peroxidation, caspase cleavage, and gasdermin D activation, in vitro experiments showed increased cytotoxicity across resistant cancer cell lines. Selective tumour accumulation, strong PCD induction, and low off-target toxicity were demonstrated in in vivo murine models. Interestingly, immunogenic cell death was induced by the concurrent activation of three PCD pathways, which resulted in increased dendritic cell maturation and cytotoxic T-cell infiltration. Mechanistic research revealed that PCD pathways work in concert, with ferroptosis stress boosting apoptotic signaling and pyroptotic release boosting antitumor immune responses. Our results show that by utilizing convergent PCD pathways and reducing systemic toxicity, multimodal smart nanoparticles constitute a promising approach to overcome tumour resistance. Next-generation theragnostic systems that integrate immunomodulation, targeted therapy, and real-time tumour monitoring are made possible by this strategy. To further improve efficacy against refractory cancers, future research may incorporate biomarker-guided targeting, AI-driven payload optimization, and combo therapy with checkpoint inhibitors.
References
1. Piña-Sánchez, P., Chávez-González, A., Ruiz-Tachiquín, M., Vadillo, E., Monroy-García, A., Montesinos, J. J., Grajales, R., De La Barrera, M. G., & Mayani, H. (2021). Cancer Biology, Epidemiology, and Treatment in the 21st Century: Current status and future challenges from a biomedical perspective. Cancer Control, 28, 10732748211038735. https://doi.org/10.1177/10732748211038735
2. Luo, Q., & Smith, D. P. (2025). Global cancer burden: progress, projections, and challenges. The Lancet, 406(10512), 1536–1537. https://doi.org/10.1016/s0140-6736(25)01570-3
3. Sikkander, A. M., Bassyouni, F., Yasmeen, K., Mishra, S. R., & Lakshmi, V. V. (2023). Synthesis of zinc oxide and lead nitrate nanoparticles and their applications: Comparative studies of bacterial and fungal (E. coli, A. niger). Journal of Applied Organometallic Chemistry, 3 (4), 255–267. https://doi.org/10.48309/JAOC.2023.41588
4. Sikkander, A. R. M., Vedhi, C., & Manisankar, P. (2012). Electrochemical determination of calcium channel blocker drugs using multiwall carbon nanotube-modified glassy carbon electrode. International Journal of Industrial Chemistry, 3, 29. https://doi.org/10.1186/2228-5547-3-29
5. Sikkander, A. R. M., Meena, M., Yadav, H., Wahi, N., & Lakshmi, V. V. (2024). Appraisal of the impact of applying organometallic compounds in cancer therapy. Journal of Applied Organometallic Chemistry, 4(2), 145–166. https://doi.org/10.48309/JAOC.2024.433120.1154
6. Sikkander, A. R. M., Yadav, H., Meena, M., Wahi, N., & Kumar, K. (2024). A review of diagnostic nano stents: Part I. Journal of Chemical Reviews, 6(2), 138–180. https://doi.org/10.48309/JCR.2024.432947.1287
7. Mohamed Sikkander, A. R., Yadav, H., Meena, M., Wahi, N., & Kumar, K. (2024). A review of diagnostic nano stents: Part I. Journal of Chemical Reviews, 6(2), 138–180. https://doi.org/10.48309/jcr.2024.432947.1287
8. Mohamed Sikkander, A. R., Yadav, H., Meena, M., & Lakshmi, V. V. (2024). A review of advances in the development of bioresorbable nano stents: Part II. Journal of Chemical Reviews, 6(3),304–330. https://doi.org/10.48309/jcr.2024.432944.1286
9. Sikkander, A. M. (2022). Intrathecal chemotherapy for blood cancer treatment. Zenodo. https://doi.org/10.5281/zenodo.7008901
10. Utilization of sodium montmorillonite clay for enhanced electrochemical sensing of amlodipine. (n.d.). Indian Journal of Chemistry. https://doi.org/10.56042/ijca.v55i5.11669
11. Wang, S., Guo, S., Guo, J., Du, Q., Wu, C., Wu, Y., & Zhang, Y. (2024). Cell death pathways: molecular mechanisms and therapeutic targets for cancer. MedComm, 5(9), e693. https://doi.org/10.1002/mco2.693
12. Griffioen, A.W., Nowak-Sliwinska, P. A cellular danse macabre: the choreography of programmed cell death. Apoptosis 30, 507–511 (2025). https://doi.org/10.1007/s10495-025-02076-2
13. Yuan, J., Ofengeim, D. A guide to cell death pathways. Nat Rev Mol Cell Biol 25, 379–395 (2024). https://doi.org/10.1038/s41580-023-00689-6
14. Yuan, J., Lipinski, M., & Degterev, A. (2003). Diversity in the mechanisms of neuronal cell death. Neuron, 40(2), 401-413.
15. Sikkander, A. M. (2022). Assess of hydrazine sulphate (N₂H₆SO₄) in opposition for the majority of cancer cells. Acta Biology Forum, 1(1), 10–13. http://dx.doi.org/10.5281/zenodo.7008883
16. Sikkander, A. R. M. (2024). Ruthenium organometallic compounds in cancer treatment. Biomedical Engineering: Applications, Basis and Communications, 37(1). https://doi.org/10.4015/s1016237224300037
17. Sikkander, A. R. M., Tripathi, S. L., & Theivanathan, G. (2025). Extensive sequence analysis: Revealing genomic knowledge throughout various domains. In Elsevier eBooks (pp. 17–30). https://doi.org/10.1016/b978-0-443-30080-6.00007-9
18. Sikkander, A. (2022). Duct cancer evaluation in situ – Review. Zenodo. https://doi.org/10.5281/zenodo.7008689
19. Sikkander, M., & Nasri, N. S. (2014). Review on inorganic nanocrystals: Unique benchmark of nanotechnology. Moroccan Journal of Chemistry, 1(2). https://doi.org/10.48317/imist.prsm/morjchem-v1i2.1892
20. Rodrigues, J. J., Sikkander, A. R. M., Tripathi, S. L., Kumar, K., Mishra, S. R., & Theivanathan, G. (2025). Healthcare applications of computational genomics. In Elsevier eBooks (pp. 259–278). https://doi.org/10.1016/b978-0-443-30080-6.00012-2
21. Islam, S., Ahmed, M. M. S., Islam, M. A., Hossain, N., & Chowdhury, M. A. (2025). Advances in nanoparticles in targeted drug delivery–A review. Results in Surfaces and Interfaces, 19, 100529. https://doi.org/10.1016/j.rsurfi.2025.100529
22. Sun, L., Liu, H., Ye, Y. et al. Smart nanoparticles for cancer therapy. Sig Transduct Target Ther 8, 418 (2023). https://doi.org/10.1038/s41392-023-01642-x
23. Rani, E.E., Sanjana, D.S., Karthikeyan, E. et al. Smart Nanomaterials: Current State and Future Prospects in Drug Delivery and Tissue Engineering. Biomedical Materials & Devices 4, 1455–1482 (2026). https://doi.org/10.1007/s44174-025-00350-0
24. Boppana, S. H., Kutikuppala, L. V. S., Sharma, S., C, M., Rangari, G., Misra, A. K., Kandi, V., Mishra, S., Singh, P. K., Rabaan, A. A., Mohapatra, R. K., & Kudrat‐E‐Zahan, M. (2024). Current approaches in smart nano‐inspired drug delivery: A narrative review. Health Science Reports, 7(4), e2065. https://doi.org/10.1002/hsr2.2065
25. Kumarasamy, R. V., Natarajan, P. M., Umapathy, V. R., Roy, J. R., Mironescu, M., & Palanisamy, C. P. (2024). Clinical applications and therapeutic potentials of advanced nanoparticles: a comprehensive review on completed human clinical trials. Frontiers in Nanotechnology, 6. https://doi.org/10.3389/fnano.2024.1479993
26. Yadav, C. H., Revanuri, N., & Sikkander, A. R. M. (2025). Tungsten-based compounds: A new frontier in cancer diagnosis and therapy. Journal of Applied Organometallic Chemistry, 5(2), 149–167. https://doi.org/10.48309/JAOC.2025.479952.1270
27. Rodrigues, J. J., Sikkander, A. R. M., Tripathi, S. L., Kumar, K., Mishra, S. R., & Theivanathan, G. (2025). Artificial intelligence’s applicability in cardiac imaging. In Elsevier eBooks (pp. 181–195). https://doi.org/10.1016/b978-0-443-30080-6.00006-7
28. Yadav, C. H., Revanuri, N., & Sikkander, A. R. M. (2025). Organometallic compound phototoxicity against cancer cells. Biomedical Engineering: Applications, Basis and Communications, 38(1). https://doi.org/10.4015/s1016237225500206
29. Mohamed Sikkander, A. R., Yadav, H., & Meena, M. (2024). The effectiveness of a nickel (II) complex containing 5-acetyl-N-(adamantan-2-yl) thiophene-2-carboxamide as a derivative for the drug isoniazid in relation to bacterial, cancer and tuberculosis activities. Advanced Journal of Chemistry, Section A, 7(5), 501–521. https://doi.org/10.48309/ajca.2024.443156.1490
30. Sikkander, A. M. (2022). Advancement of agricultural biotechnology in USA. International Journal of AgroChemistry. https://chemical.journalspub.info/index.php?journal=IJCPD&page=article&op=view&path%5B%5D=1299
31. Ramachandran, K., & Sikkander, A. M. (2021). Biomedical signal processing: Understanding its importance and several fundamental steps. Transaction on Biomedical Engineering Applications and Healthcare, 2(2), 15–16.
32. Chegini, S., Sikkander, A. R. M., Masoudi, M., Ekhtari, H., Mojaver, E., & Jafari, H. (2026). A circular bioeconomy framework for biodegradable waste: Strategies and opportunities. Bioresources and Bioproducts, 2(1), 2. https://doi.org/10.3390/bioresourbioprod2010002
33. Sikkander, A. M., Rodrigues, J. J. P. C., Meena, M., & Abuelmakarem, H. S. (2025). Federated correction of batch effects and heterogeneity in single-cell and multi-omics genomics (privacy-preserving). World Journal of Applied Medical Sciences, 2(12), 24–30. https://doi.org/10.65336/wjams.2025.21204
34. Hiremath, G., Mohamed Sikkander, A. R., Upadhyay, R., Acharya, D., Singh, K. P., & Wahi, N. (2025). Safety and efficacy of drug-eluting stents improved dramatically with application of nanotechnology. Advanced Journal of Chemistry, Section A, 8(2), 378–391. https://doi.org/10.48309/ajca.2025.467077.1591
35. Theivanathan, G., Mohamed Sikkander, A., Hemavathy, N., Murukesh, & Mishra, S. R. (2022). Tactile system for visually impaired people using embedded technology. International Journal of Scientific Research and Innovative Studies, 1(1), 14–19.
36. Sikkander, A. M., RamaNachiar, R., & Yasmeen, K. (2022). Spiking neural network (SNN) using to detect breast cancer. International Journal of Scientific Research and Innovative Studies, 1(1), 20–22.
37. Afzal, O., Altamimi, A. S. A., Nadeem, M. S., Alzarea, S. I., Almalki, W. H., Tariq, A., Mubeen, B., Murtaza, B. N., Iftikhar, S., Riaz, N., & Kazmi, I. (2022). Nanoparticles in drug delivery: From history to therapeutic applications. Nanomaterials, 12(24), 4494. https://doi.org/10.3390/nano12244494
38. Abed, A., Mirzaei, S.A., Hosseini, S.A. et al. Metal nanoparticles and sensitivity/resistance to therapy in cancer: two sides of the coin?. J Nanopart Res 27, 44 (2025). https://doi.org/10.1007/s11051-025-06228-y
39. Chen, Z., Wang, W., Abdul Razak, S.R. et al. Ferroptosis as a potential target for cancer therapy. Cell Death Dis 14, 460 (2023). https://doi.org/10.1038/s41419-023-05930-w
40. Degirmenci, N.S., Yildirim, Z., Padar, G. et al. Combination of sodium pentaborate pentahydrate, curcumin and piperine treatment induces ferroptosis in hepatocellular carcinoma cells by regulating iron homeostasis and ROS activity in vitro. Med Oncol 43, 129 (2026). https://doi.org/10.1007/s12032-025-03223-0
41. Degirmenci, N.S., Yildirim, Z., Padar, G. et al. Combination of sodium pentaborate pentahydrate, curcumin and piperine treatment induces ferroptosis in hepatocellular carcinoma cells by regulating iron homeostasis and ROS activity in vitro. Med Oncol 43, 129 (2026). https://doi.org/10.1007/s12032-025-03223-0
42. Madappan, D., Krishnegowda, M.B., Naik, P. et al. Ferroptosis-centered strategies: redefining therapeutic resistance & adaptation in modern oncology. Apoptosis 31, 62 (2026). https://doi.org/10.1007/s10495-026-02279-1
43. Sikkander, A. M., RamaNachiar, R., & Yasmeen, K. (2022). Artificial neural networks (ANNs) in lung cancer detection. International Journal of Scientific Research and Innovative Studies, 1(1), 155–158.
44. Sikk, A. M., & Abbas, H. S. (n.d.). A novel biosensor for pathogens diagnosis. https://www.alliedacademies.org/articles/a-novel-biosensor-for-pathogens-diagnosis-17372.
45. Sikkander, A. M., & Yasmeen, K. (2021). Review on nanotechnology: Curative applications in the medicinal field and its adverse effects.Journal of Science and Technology, 6(2), 1–8. https://doi.org/10.46243/jst.2021.v6.i2.pp01-08
46. Sikkander, M., Vedhi, C., & Manisankar, P. (2014). Enhanced electrochemical sensing of nimodipine with sodium montmorillonite clay. Moroccan Journal of Chemistry. https://doi.org/10.48317/imist.prsm/morjchem-v2i4.2135
47. Sikkander, A. M., Rodrigues, J. J. P. C., Meena, M., & Abuelmakarem, H. S. (2025). AI-powered generative frameworks for the rational design of synthetic genomes and next-generation cellular architectures. World Journal of Multidisciplinary Studies, 2(12), 46–53. https://doi.org/10.65336/wjms.2025.21204
48. Sikkander, A. M., Rodrigues, J. J. P. C., Meena, M., & Abuelmakarem, H. S. (2025). Leveraging artificial intelligence to integrate genomics, transcriptomics, and proteomics data for enhanced disease prediction. World Journal of Applied Medical Sciences, 2(12), 31–39. https://doi.org/10.65336/wjams.2025.21205
49. Sikkander, A. M., Rodrigues, J. J. P. C., Meena, M., & Abuelmakarem, H. S. (2025). Trustworthy and transparent AI for genomic discovery.World Journal of Multidisciplinary Studies, 2(12), 39–45. https://doi.org/10.65336/wjms.2025.21203
50. Sikkander, A. M., Rodrigues, J. J. P. C., Meena, M., & Abuelmakarem, H. S. (2025). Intelligent visualization frameworks driven by AI for multi-dimensional genomic data exploration and interpretation. World Journal of Multidisciplinary Studies, 2(12), 31–38. https://doi.org/10.65336/wjms.2025.21202
51. Sikkander, A. M., Rodrigues, J. J. P. C., Meena, M., & Abuelmakarem, H. S. (2025). AI-driven genomic biomarker discovery for precision diagnosis and personalized treatment. World Journal of Applied Medical Sciences, 2(12), 14–23. https://doi.org/10.65336/wjams.2025.21203
52. Sikkander, A. M., Rodrigues, J. J. P. C., Abuelmakarem, H. S., & Meena, M. (2025, November 28). Nanotechnology beneath: Innovations fuelling advances in acute care medicine, cardiology, oncology, and hypertension. https://wasrpublication.com/index.php/wjams/article/view/181
53. de la Lastra, J.M.P., Andrés, C.M.C., Munguira, E.B. et al. Pathophysiology of reactive oxygen species (ROS). Arch Toxicol 100, 475–513 (2026). https://doi.org/10.1007/s00204-025-04276-w
54. Pan, X., Chen, K., Gao, W. et al. Circular RNA circBNC2 inhibits tumorigenesis by modulating ferroptosis and acts as a nanotherapeutic target in prostate cancer. Mol Cancer 24, 29 (2025). https://doi.org/10.1186/s12943-025-02234-9
55. Sikkander, A. M., Rodrigues, J. J. P. C., Abuelmakarem, H. S., & Meena, M. (2025, November 26). Biomedical engineering innovations driving breakthroughs in cardiology, oncology, hypertension, and acute care medicine. https://wasrpublication.com/index.php/wjams/article/view/180
56. Sikkander, A. M., Rodrigues, J. J. P. C., Abuelmakarem, H. S., & Meena, M. (2025, November 24). AI beneath: Innovations driving breakthroughs in cardiology, oncology, hypertension, and acute care medicine. https://wasrpublication.com/index.php/wjams/article/view/179
57. Sikkander, A. M., Yadav, C. H., & Revanuri, N. (2025, November 21). Current developments in cyclophosphamide for lymphoma: Immunomodulation, metronomic approaches, and toxicity control. https://wasrpublication.com/index.php/wjams/article/view/177
58. Sikkander, A. M., Yadav, C. H., & Revanuri, N. (2025). A meta-analysis in non–small-cell lung cancer (NSCLC) indicates glucocorticoid administration is significantly associated with worse progression-free survival and overall survival for patients on ICIs. https://wasrpublication.com/index.php/wjams/article/view/176
59. Sikkander, A. R. M., Mishra, S. R., Shankaranarayanan, S., & Chegini, S. (2025). The iPSC-based models for hereditary arrhythmias: From genotype–phenotype studies to precision therapy. SPC Journal of Medical and Healthcare, 1(3), 184–191. https://doi.org/10.48309/sjmh.2025.537906.107
60. Mohamed Sikkander, A. R., Chegini, S., Mishra, S. R., & Subramanian, S. (2025). Integration of 6G networks and deep learning for advanced biomedical engineering applications: Real-time analytics, remote surgery, and intelligent healthcare systems. SPC Journal of Medical and Healthcare, 1(3), 167–175. https://doi.org/10.48309/sjmh.2025.537895.1073
61. Sikkander, A. R. M., Lakshmi, V. V., Theivanathan, G., & Radhakrishnan, K. (2024). Multiresolution evaluation of contourlet transform for the diagnosis of skin cancer. SSR Preprints. https://doi.org/10.21203/rs.3.rs-4778827/v1
62. Sikkander, A. M., Yasmeen, K., & Haseeb, M. (2024). Biological synthesis, characterization, and therapeutic utility of Fusarium oxysporum silver nanoparticles. SSR Preprints. https://doi.org/10.21203/rs.3.rs-4649729/v1
63. Sikkander, A. M. (2022, October 3). Nanosilicones in sub-glandular and sub-muscular implant breast transplantation. International Journal of Analytical and Applied Chemistry. https://chemical.journalspub.info/index.php?journal=JAAC&page=article&op=view&path%5B%5D=1309
64. Sikkander, A. M. (2022, September 19). Assessment of basal cell carcinoma. International Journal of Chemical and Molecular Engineering. https://chemical.journalspub.info/index.php?journal=JCME&page=article&op=view&path%5B%5D=1311
65. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71:209–49.
66. Anand, U., Dey, A., Chandel, A. K. S., Sanyal, R., Mishra, A., Pandey, D. K., De Falco, V., Upadhyay, A., Kandimalla, R., Chaudhary, A., Dhanjal, J. K., Dewanjee, S., Vallamkondu, J., & De La Lastra, J. M. P. (2022). Cancer chemotherapy and beyond: Current status, drug candidates, associated risks and progress in targeted therapeutics. Genes & Diseases, 10(4), 1367–1401. https://doi.org/10.1016/j.gendis.2022.02.007
67. Zafar, A., Khan, M.J., Abu, J. et al. Revolutionizing cancer care strategies: immunotherapy, gene therapy, and molecular targeted therapy. Mol Biol Rep 51, 219 (2024). https://doi.org/10.1007/s11033-023-09096-8
68. Miao, H., Fang, Y., Pan, C., Yang, H., Wang, Z., Qi, Y., Wu, Y., Zhang, Y., Liu, F., Huang, H., Tang, Y., Wu, D., & Li, N. (2025). Transforming the landscape of cancer treatment with seven promising novel therapies: evolution and future perspectives. Medicine Plus, 2(2), 100087. https://doi.org/10.1016/j.medp.2025.100087
69. Ghemrawi, R., Abuamer, L., Kremesh, S., Hussien, G., Ahmed, R., Mousa, W., Khoder, G., & Khair, M. (2024). Revolutionizing Cancer Treatment: Recent Advances in Immunotherapy. Biomedicines, 12(9), 2158. https://doi.org/10.3390/biomedicines12092158
70. Maqbool, H., Yasin, U., Shawal, L., Zulfiqar, F., Fatima, N., Hasan, W., Nasim, H., Ismail, M., & Rafiq, M. (2024). ADVANCEMENTS IN CANCER PHARMACOTHERAPY: TARGETED THERAPIES AND IMMUNOTHERAPY STRATEGIES, a REVIEW. Biological and Clinical Sciences Research Journal, 2024(1), 1025. https://doi.org/10.54112/bcsrj.v2024i1.1025
71. Sikkander, A. M. (2022, September 17). Nanoemulsion in ophthalmology.International Journal of Chem-Informatics Research. https://chemical.journalspub.info/index.php?journal=JAWCM&page=article&op=view&path%5B%5D=1310
72. Sikkander, M., & Abbas, H. S. (2021). Biosensors for pathogens diagnosis. Journal of Chemical Technology Applications, 2(2), 1–3. https://www.alliedacademies.org/articles/biosensors-for-pathogens-diagnosis.pdf
73. Sikk, M., Er, A., & Yasmeen, K. (n.d.). Evaluation of surgical risk in patients with liver cancer. https://doi.org/10.35841/aaccr-5.3.115
74. Sikkander, A. M., Yadav, C. H., & Revanuri, N. (2025). Recent trends in Oncovin (vincristine) use for acute lymphoblastic leukemia: Liposomal formulations, pharmacogenomics, and toxicity-mitigation strategies. ISAR Journal of Medical and Pharmaceutical Sciences, 3(11), 20–23.
75. Sikkander, A. R. M., & Rodrigues, J. J. P. C. (2026, January 28). Machine learning models to predict chemotherapy resistance in breast cancer using single-cell sequencing. https://wasrpublication.com/index.php/wjams/article/view/219
76. Sikkander, A. R. M., & Rodrigues, J. J. P. C. (2026, January 27). Deep-learning models for ultrasound, mammography, and MRI fusion for accurate tumor segmentation. https://wasrpublication.com/index.php/wjams/article/view/218
77. Sikkander, A. M., Yadav, C. H., & Revanuri, N. (2025). Current trends: Recent innovations and impacts of flap necrosis in breast reduction. ISAR Journal of Medical and Pharmaceutical Sciences, 3(11), 12–19.
78. Razak, M. S. A., Lakshmi, V. V., & Rodrigues, J. J. P. C. (2025). Multiresolution analysis of wavelets using artificial intelligence for skin cancer detection. SSRN Electronic Journal. https://doi.org/10.2139/ssrn.5142172
79. Razak, M. S. A., Lakshmi, V. V., Theivanathan, G., & Radhakrishnan, K. (2025). Artificial intelligence-driven multidirectional curvelet analysis for enhanced skin cancer detection. SSRN Electronic Journal. https://doi.org/10.2139/ssrn.5127060
80. Gupta, J. K., Sikkander, A. R. M., Nagrami, F. U. H., Kumar, K., & Wahi, N. (2023). Appraisal, recent advancement, and impacts of nanomedicine in cardiac asthma. Journal of Medical Pharmaceutical and Allied Sciences, 12(5), 6132–6138. https://doi.org/10.55522/jmpas.v12i5.5214
81. Carneiro, B.A., El-Deiry, W.S. Targeting apoptosis in cancer therapy. Nat Rev Clin Oncol 17, 395–417 (2020). https://doi.org/10.1038/s41571-020-0341-y
82. Indran, I. R., Tufo, G., Pervaiz, S., & Brenner, C. (2011). Recent advances in apoptosis, mitochondria and drug resistance in cancer cells. Biochimica Et Biophysica Acta (BBA) - Bioenergetics, 1807(6), 735–745. https://doi.org/10.1016/j.bbabio.2011.03.010
83. Hu, W., & Kavanagh, J. J. (2003). Anticancer therapy targeting the apoptotic pathway. The Lancet Oncology, 4(12), 721–729. https://doi.org/10.1016/s1470-2045(03)01277-4
84. Singh, V., Khurana, A., Navik, U., Allawadhi, P., Bharani, K. K., & Weiskirchen, R. (2022). Apoptosis and Pharmacological Therapies for Targeting Thereof for Cancer Therapeutics. Sci, 4(2), 15. https://doi.org/10.3390/sci4020015
85. Zhang, X., Xiang, Y., Wang, Q., Bai, X., Meng, D., Wu, J., Sun, K., Zhang, L., Qiang, R., Liu, W., Zhang, X., Qiang, J., Liu, X., & Yang, Y. (2025). Regulation of iron metabolism in ferroptosis: From mechanism research to clinical translation. Journal of Pharmaceutical Analysis, 15(10), 101304. https://doi.org/10.1016/j.jpha.2025.101304
86. Yadav, C. H., Revanuri, N., & Mohamed Sikkander, A. R. (2025). Organometallic compound phototoxicity against cancer cells. Biomedical Engineering: Applications, Basis and Communications. https://doi.org/10.4015/S1016237225500206
87. Sikkander, A. M., Ranjan, R., & Mishra, S. R. (2024). Artificial intelligence in cerebellum activation. International Journal of Cheminformatics, 1(1), 14–26. https://journals.stmjournals.com/ijci/article=2024/view=143947
88. Mohamed Sikkander, A. R., Ranjan, R., & Mishra, S. R. (2024). Nanoelectronics, nanoparticles, and nanotechnology in treatment of psychological disorders. International Journal of Environmental Chemistry. https://journals.stmjournals.com/ijec/article=2024/view=143513
89. Sikkander, A. M., Ranjan, R., & Sikkander, A. M. (2024). Organometallic osmium compounds in cancer therapy. International Journal of Advance in Molecular Engineering, 1(2), 1–25. https://journals.stmjournals.com/ijame/article=2024/view=144940
90. Mohamed Sikkander, A. R. (2024). Catalytic activity advancements in organometallic chemistry. https://engineeringjournals.stmjournals.in/index.php/JoCC/issue/view/1274
91. Shen, G., Liu, J., Wang, Y., Deng, Z., & Deng, F. (2025). Ferroptosis in Cancer and Inflammatory Diseases: Mechanisms and therapeutic implications. MedComm, 6(9), e70349. https://doi.org/10.1002/mco2.70349
92. Jin, X., Tang, J., Qiu, X. et al. Ferroptosis: Emerging mechanisms, biological function, and therapeutic potential in cancer and inflammation. Cell Death Discov. 10, 45 (2024). https://doi.org/10.1038/s41420-024-01825-7
93. Wang, J., Guo, D., Jiang, S. et al. Targeting ferroptosis in cancer: from mechanistic insights to therapeutic approaches. Mol Biomed 7, 20 (2026). https://doi.org/10.1186/s43556-026-00416-5
94. Asiedu, R.K.F., Souley Abdou, M., Wei, R. et al. Harnessing pyroptosis in breast cancer therapy: immunological mechanisms and emerging biomaterial strategies. Cell Death Discov. (2026). https://doi.org/10.1038/s41420-026-02996-1
95. Gupta, J. K., Sikkander, A. R. M., Nagrami, F. U. H., Kumar, K., & Wahi, N. (2023). Appraisal, recent advancement, and impacts of nanomedicine in cardiac asthma. Journal of Medical Pharmaceutical and Allied Sciences, 12(5), 6132–6138. https://doi.org/10.55522/jmpas.v12i5.5214
96. Sikkander, A. M. (2022). Nanosilicones in sub-glandular and sub-muscular implant breast transplantation. International Journal of Analytical and Applied Chemistry. https://chemical.journalspub.info/index.php?journal=JAAC&page=index
97. Sikkander, A. M. (2022). Assessment of basal cell carcinoma. International Journal of Chemical and Molecular Engineering, 8(2). https://chemical.journalspub.info/index.php?journal=JCME&page=issue&op=view&path%5B%5D=273
98. 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
99. Sikkander, A. M. (2022). Nanoemulsion in ophthalmology. International Journal of Chem-Informatics Research, 8(2). https://chemical.journalspub.info/index.php?journal=JAWCM&page=index
100. Sikkander, A. M. (2023). Advancement of agricultural biotechnology in USA. International Journal of AgroChemistry, 9(2). https://chemical.journalspub.info/index.php?journal=IJCPD&page=index
101. Ko, M. J., Min, S., Hong, H., Yoo, W., Joo, J., Zhang, Y. S., Kang, H., & Kim, D. (2023). Magnetic nanoparticles for ferroptosis cancer therapy with diagnostic imaging. Bioactive Materials, 32, 66–97. https://doi.org/10.1016/j.bioactmat.2023.09.015
102. Wei, Y., Han, B., Hu, X., Lin, Y., Wang, X., & Deng, X. (2012). Synthesis of Fe3O4 Nanoparticles and their Magnetic Properties. Procedia Engineering, 27, 632–637. https://doi.org/10.1016/j.proeng.2011.12.498
103. Van Acker, T., Theiner, S., Bolea-Fernandez, E. et al. Inductively coupled plasma mass spectrometry. Nat Rev Methods Primers 3, 52 (2023). https://doi.org/10.1038/s43586-023-00235-w
104. Huang, B., Wang, H., Liu, S. et al. Palmitoylation-dependent regulation of GPX4 suppresses ferroptosis. Nat Commun 16, 867 (2025). https://doi.org/10.1038/s41467-025-56344-5
105. Bai, JW., Qiu, SQ. & Zhang, GJ. Molecular and functional imaging in cancer-targeted therapy: current applications and future directions. Sig Transduct Target Ther 8, 89 (2023). https://doi.org/10.1038/s41392-023-01366-y
106. Malm, A.V., Corbett, J.C.W. Improved Dynamic Light Scattering using an adaptive and statistically driven time resolved treatment of correlation data. Sci Rep 9, 13519 (2019). https://doi.org/10.1038/s41598-019-50077-4
107. Monteleone, M., Stanley, A. C., Chen, K. W., Brown, D. L., Bezbradica, J. S., Von Pein, J. B., Holley, C. L., Boucher, D., Shakespear, M. R., Kapetanovic, R., Rolfes, V., Sweet, M. J., Stow, J. L., & Schroder, K. (2018). Interleukin-1β Maturation Triggers Its Relocation to the Plasma Membrane for Gasdermin-D-Dependent and -Independent Secretion. Cell Reports, 24(6), 1425–1433. https://doi.org/10.1016/j.celrep.2018.07.027
108. Archetti, C., Peirano, L., & Speranza, M. G. (2021c). Optimization in multimodal freight transportation problems: A Survey. European Journal of Operational Research, 299(1), 1–20. https://doi.org/10.1016/j.ejor.2021.07.031.
109. O’Melia, M. J., Rohner, N. A., Manspeaker, M. P., Francis, D. M., Kissick, H. T., & Thomas, S. N. (2020). Quality of CD8 + T cell immunity evoked in lymph nodes is compartmentalized by route of antigen transport and functional in tumor context. Science Advances, 6(50). https://doi.org/10.1126/sciadv.abd7134
110. Li, X., Peng, X., Zoulikha, M. et al. Multifunctional nanoparticle-mediated combining therapy for human diseases. Sig Transduct Target Ther 9, 1 (2024). https://doi.org/10.1038/s41392-023-01668-1
111. Adzavon, K. P., Zhao, W., He, X., & Sheng, W. (2024b). Ferroptosis resistance in cancer cells: nanoparticles for combination therapy as a solution. Frontiers in Pharmacology, 15, 1416382. https://doi.org/10.3389/fphar.2024.1416382
112. Passaro, A., Bakir, M. A., Hamilton, E. G., Diehn, M., André, F., Roy-Chowdhuri, S., Mountzios, G., Wistuba, I. I., Swanton, C., & Peters, S. (2024). Cancer biomarkers: Emerging trends and clinical implications for personalized treatment. Cell, 187(7), 1617–1635. https://doi.org/10.1016/j.cell.2024.02.041
113. Goswami, S., Pauken, K.E., Wang, L. et al. Next-generation combination approaches for immune checkpoint therapy. Nat Immunol 25, 2186–2199 (2024). https://doi.org/10.1038/s41590-024-02015-4
114. Bae, H., Ji, H., Konstantinov, K., Sluyter, R., Ariga, K., Kim, Y. H., & Kim, J. H. (2025). Artificial Intelligence‐Driven Nanoarchitectonics for smart targeted drug delivery. Advanced Materials, 37(42), e10239. https://doi.org/10.1002/adma.202510239
115. Hosseini, S., Mohammadnejad, J., Salamat, S., Zadeh, Z. B., Tanhaei, M., & Ramakrishna, S. (2023). Theranostic polymeric nanoparticles as a new approach in cancer therapy and diagnosis: a review. Materials Today Chemistry, 29, 101400. https://doi.org/10.1016/j.mtchem.2023.101400
116. Li, Y., Pan, X., Hai, P., Zheng, Y., Shan, Y., & Zhang, J. (2024). All-in-one nanotheranostic platform based on tumor microenvironment: new strategies in multimodal imaging and therapeutic protocol. Drug Discovery Today, 29(7), 104029. https://doi.org/10.1016/j.drudis.2024.104029
117. Pan, Y., Xue, X., & Liang, X. (2024). Nanotechnology‐Empowered Combination Cancer Immunotherapies: Mechanisms, synergies, and perspectives. Advanced NanoBiomed Research, 4(4). https://doi.org/10.1002/anbr.202300129
118. Lei, W., Zhou, K., Lei, Y. et al. Cancer vaccines: platforms and current progress. Mol Biomed 6, 3 (2025). https://doi.org/10.1186/s43556-024-00241-8
119. Lei, W., Zhou, K., Lei, Y. et al. Cancer vaccines: platforms and current progress. Mol Biomed 6, 3 (2025). https://doi.org/10.1186/s43556-024-00241-8
120. Gu, Y., Yang, R., Zhang, Y. et al. Molecular mechanisms and therapeutic strategies in overcoming chemotherapy resistance in cancer. Mol Biomed 6, 2 (2025). https://doi.org/10.1186/s43556-024-00239-2
121. Crucitta, S., Cucchiara, F., Mathijssen, R., Mateo, J., Jager, A., Joosse, A., Passaro, A., Attili, I., Petrini, I., Van Schaik, R., Danesi, R., & Del Re, M. (2022). Treatment-driven tumour heterogeneity and drug resistance: Lessons from solid tumours. Cancer Treatment Reviews, 104, 102340. https://doi.org/10.1016/j.ctrv.2022.102340
122. Youssef, E., Fletcher, B., & Palmer, D. (2025). Enhancing precision in cancer treatment: the role of gene therapy and immune modulation in oncology. Frontiers in Medicine, 11, 1527600. https://doi.org/10.3389/fmed.2024.1527600
123. Nussinov, R., Weichhart, T., Dlamini, Z., Gibbons, D. L., Van Seuningen, I., Konen, J., & Ju, H. (2024). Directions to overcome therapy resistance in cancer. Trends in Pharmacological Sciences, 45(6), 467–471. https://doi.org/10.1016/j.tips.2024.05.001
