Cancer medicine has stepped into the era of multidisciplinary treatments, calling for synergistic therapeutic regimens. Single therapeutic strategies, including chemotherapy, radiotherapy, surgical treatment, targeted therapy, and immunotherapy, are no longer sufficient to support cancer treatment. Various therapeutic systems based on antibody-drug-nanoparticle conjugates (ADNCs) have been developed as promising strategies for more effective cancer therapy. The rapid advances in nanotechnology, molecular biology, pharmacy and immunology have driven the innovative development of actively targeted nanoparticles for safer and more effective precision cancer therapy. With excellent targeting capability, ADNCs can act as efficient drug carriers and tumor microenvironment (TME) regulators. In this review, we focus on the classification, structure, and applications of monoclonal antibodies (mAbs), as well as the conjugation between antibodies and nanocarriers. Meanwhile, we systematically summarize the latest progress in nanoparticles (NPs) as mainstream drug delivery systems, such as liposomes, nanoemulsions, dendrimers, carbon-based NPs, polymeric NPs, and metallic NPs. Furthermore, we discuss the design and optimization of ADNCs. Despite the tremendous potential of ADNCs, we also admit their shortcomings and challenges associated with their implementation and the clinical applications. This review aims to propose a novel and synergistic perspective of ADNCs in precision and personalized cancer treatment, offering patient-specific therapeutic alternatives for clinical practice.
References
[1] Bray, F., Laversanne, M., Sung, H., Ferlay, J., Siegel, R. L., Soerjomataram, I., Jemal, A. (2024) Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 74(3), 229-263.
[2] Peña, Q., Wang, A., Zaremba, O., Shi, Y., Scheeren, H. W., Metselaar, J. M., Kiessling, F., Pallares, R. M., Wuttke, S., Lammers, T. (2022) Metallodrugs in cancer nanomedicine. Chemical Society Reviews, 51(7), 2544-2582.
[3] Sun, L., Liu, H., Ye, Y., Lei, Y., Islam, R., Tan, S., Tong, R., Miao, Y. B., Cai, L. (2023) Smart nanoparticles for cancer therapy. Signal Transduction and Targeted Therapy, 8(1), 418.
[4] Fan, D., Cao, Y., Cao, M., Wang, Y., Cao, Y., Gong, T. (2023) Nanomedicine in cancer therapy. Signal Transduction and Targeted Therapy, 8(1), 293.
[5] Matsumura, Y., Maeda, H. (1986) A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Research, 46(12), 6387-6392.
[6] Zinn, S., Vazquez-Lombardi, R., Zimmermann, C., Sapra, P., Jermutus, L., Christ, D. (2023) Advances in antibody-based therapy in oncology. Nature Cancer, 4(2), 165-180.
[7] Kelley, B. (2024) The history and potential future of monoclonal antibody therapeutics development and manufacturing in four eras. Mabs, 16(1), 2373330.
[8] Drago, J. Z., Modi, S., Chandarlapaty, S. (2021) Unlocking the potential of antibody-drug conjugates for cancer therapy. Nature Reviews Clinical Oncology, 18(6), 327-344.
[9] Köhler, G., Milstein, C. (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature, 256(5517), 495-497.
[10] Elias, D. J., Hirschowitz, L., Kline, L. E., Kroener, J. F., Dillman, R. O., Walker, L. E., Robb, J. A., Timms, R. M. (1990) Phase I clinical comparative study of monoclonal antibody KS1/4 and KS1/4-methotrexate immunconjugate in patients with non-small cell lung carcinoma. Cancer Research, 50(13), 4154-4159.
[11] Bross, P. F., Beitz, J., Chen, G., Chen, X. H., Duffy, E., Kieffer, L., Roy, S., Sridhara, R., Rahman, A., Williams, G., Pazdur, R. (2001) Approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia. Clinical Cancer Research, 7(6), 1490-1496.
[12] Dumontet, C., Reichert, J. M., Senter, P. D., Lambert, J. M., Beck, A. (2023) Antibody-drug conjugates come of age in oncology. Nature Reviews Drug Discovery, 22(8), 641-661.
[13] Sivaram, A. J., Wardiana, A., Howard, C. B., Mahler, S. M., Thurecht, K. J. (2018) Recent advances in the generation of antibody-nanomaterial conjugates. Advanced Healthcare Materials, 7(1), 1700607.
[14] Lin, X., Beringhs, A. O., Lu, X. (2021) Applications of nanoparticle-antibody conjugates in immunoassays and tumor imaging. The AAPS Journal, 23(2), 43.
[15] Adhikari, A., Chen, I. A. (2025) Antibody‐Nanoparticle conjugates in therapy: combining the best of two worlds. Small, 21(15), 2409635.
[16] Mantovani, A., Allavena, P., Marchesi, F., Garlanda, C. (2022) Macrophages as tools and targets in cancer therapy. Nature Reviews Drug Discovery, 21(11), 799-820.
[17] Yang, M., Li, J., Gu, P., Fan, X. (2021) The application of nanoparticles in cancer immunotherapy: targeting tumor microenvironment. Bioactive materials, 6(7), 1973-1987.
[18] Vincken, R., Armendáriz-Martínez, U., Ruiz-Sáenz, A. (2025) ADCC: the rock band led by therapeutic antibodies, tumor and immune cells. Frontiers in Immunology, 16, 1548292.
[19] Van Wagoner, C. M., Rivera‐Escalera, F., Jaimes‐Delgadillo, N. C., Chu, C. C., Zent, C. S., Elliott, M. R. (2023) Antibody‐mediated phagocytosis in cancer immunotherapy. Immunological Reviews, 319(1), 128-141.
[20] Rashid, M. H. (2022) Full-length recombinant antibodies from Escherichia coli: production, characterization, effector function (Fc) engineering, and clinical evaluation. Mabs, 14(1), 2111748.
[21] Shah, A., Rauth, S., Aithal, A., Kaur, S., Ganguly, K., Orzechowski, C., Varshney, G. C., Jain, M., Batra, S, K,. Batra, S. K. (2021) The current landscape of antibody-based therapies in solid malignancies. Theranostics, 11(3), 1493.
[22] Jin, Y., Schladetsch, M. A., Huang, X., Balunas, M. J., Wiemer, A. J. (2022) Stepping forward in antibody-drug conjugate development. Pharmacology & Therapeutics, 229, 107917.
[23] Kang, M. S., Kong, T. W. S., Khoo, J. Y. X., Loh, T. P. (2021) Recent developments in chemical conjugation strategies targeting native amino acids in proteins and their applications in antibody-drug conjugates. Chemical Science, 12(41), 13613-13647.
[24] Hassanin, I. A., Elzoghby, A. O. (2020) Self-assembled non-covalent protein-drug nanoparticles: an emerging delivery platform for anti-cancer drugs. Expert Opinion on Drug Delivery, 17(10), 1437-1458.
[25] Krall, N., Da Cruz, F. P., Boutureira, O., Bernardes, G. J. (2016) Site-selective protein-modification chemistry for basic biology and drug development. Nature Chemistry, 8(2), 103-113.
[26] Boide-Trujillo, V. J., Mittelheisser, V., Liu, F., Lefebvre, O., Andreiuk, B., Anton, N., Goetz, J. G., Klymchenko, A. S. (2025) Functionalization of lipid nanoemulsions with humanized antibodies using plug-and-play cholesterol anchor for targeting cancer cells. Nanoscale Advances, 7(22), 7226-7238.
[27] Botcha, A.K., Yemineni, Y. S. L V. (2025) Synthesis and characterization of thiol-stabilized gold nanoparticles appended to bis (pyrazole) pyridine for fabrication of rectangular nano/microstripes and their spin crossover and SERS studies. RSC Advances, 15(38), 31461-31470.
[28] Du, C., Jiang, J., Wan, C., Pan, G., Kong, F., Zhai, R., Hu, C., Ying, H. (2022) AntiPD-L1 antibody conjugated Au-SPIOs nanoplatform for enhancing radiosensitivity and triggering anti-tumor immune response. Scientific Reports, 12(1), 19542.
[29] Hashad, R. A., Singla, R., Bhangu, S. K., Jap, E., Zhu, H., Peleg, A. Y., Blakeway, L., Hagemyer, C. E., Cavalieri, F., Ashokkumar, M., Alt, K. (2022) Chemoenzymatic surface decoration of Nisin-shelled nanoemulsions: Novel targeted drug-nanocarriers for cancer applications. Ultrasonics Sonochemistry, 90, 106183.
[30] Cheng, Z., Li, M., Dey, R., Chen, Y. (2021) Nanomaterials for cancer therapy: current progress and perspectives. Journal of Hematology & Oncology, 14(1), 85.
[31] Xu, B., Li, S., Shi, R., Liu, H. (2023) Multifunctional mesoporous silica nanoparticles for biomedical applications. Signal Transduction and Targeted Therapy, 8(1), 435.
[32] Silli, E. K., Li, M., Shao, Y., Zhang, Y., Hou, G., Du, J., Liang, J., Wang, Y. (2023) Liposomal nanostructures for Gemcitabine and Paclitaxel delivery in pancreatic cancer. European Journal of Pharmaceutics and Biopharmaceutics, 192, 13-24.
[33] Ahmadi, A., Hosseini-Nami, S., Abed, Z., Beik, J., Aranda-Lara, L., Samadian, H., Morales-Avila, E., Jaymand, M., Shakeri-Zadeh, A. (2020) Recent advances in ultrasound-triggered drug delivery through lipid-based nanomaterials. Drug Discovery Today, 25(12), 2182-2200.
[34] Wang, S., Chen, Y., Guo, J., Huang, Q. (2023) Liposomes for tumor targeted therapy: a review. International Journal of Molecular Sciences, 24(3), 2643.
[35] Fan, Y., Marioli, M., Zhang, K. (2021) Analytical characterization of liposomes and other lipid nanoparticles for drug delivery. Journal of Pharmaceutical and Biomedical Analysis, 192, 113642.
[36] Park, W., Choi, J., Hwang, J., Kim, S., Kim, Y., Shim, M. K., Park, W., Yu, S., Jung, S., Yang, Y., Kweon, D. H. (2025) Apolipoprotein fusion enables spontaneous functionalization of mRNA lipid nanoparticles with antibody for targeted cancer therapy. ACS Nano, 19(6), 6412-6425.
[37] Guimarães, D., Cavaco-Paulo, A., Nogueira, E. (2021) Design of liposomes as drug delivery system for therapeutic applications. International Journal of Pharmaceutics, 601, 120571.
[38] Sánchez-López, E., Guerra, M., Dias-Ferreira, J., Lopez-Machado, A., Ettcheto, M., Cano, A., Espina, M., Camins, A., Garcia, M. L., Souto, E. B. (2019) Current applications of nanoemulsions in cancer therapeutics. Nanomaterials, 9(6), 821.
[39] Gorain, B., Choudhury, H., Nair, A. B., Dubey, S. K., Kesharwani, P. (2020) Theranostic application of nanoemulsions in chemotherapy. Drug Discovery Today, 25(7), 1174-1188.
[40] Meng, L., Xia, X., Yang, Y., Ye, J., Dong, W., Ma, P., Jin, Y., Liu, Y. (2016) Co-encapsulation of paclitaxel and baicalein in nanoemulsions to overcome multidrug resistance via oxidative stress augmentation and P-glycoprotein inhibition. International Journal of Pharmaceutics, 513(1-2), 8-16.
[41] Cruz, A., Barbosa, J., Antunes, P., Bonifácio, V. D., Pinto, S. N. (2023) A glimpse into dendrimers integration in cancer imaging and theranostics. International Journal of Molecular Sciences, 24(6), 5430.
[42] Crintea, A., Motofelea, A. C., Șovrea, A. S., Constantin, A. M., Crivii, C. B., Carpa, R., Duțu, A. G. (2023) Dendrimers: advancements and potential applications in cancer diagnosis and treatment – an overview. Pharmaceutics, 15(5), 1406.
[43] Aleanizy, F. S., Alqahtani, F. Y., Seto, S., Al Khalil, N., Aleshaiwi, L., Alghamdi, M., Alquadeib, B., Alkahtani, H., Aldarwesh, A., Alqahtani, Q. H., Abdelhady, H, G., Alsarra, I. (2020) Trastuzumab targeted neratinib loaded poly-amidoamine dendrimer nanocapsules for breast cancer therapy. International Journal of Nanomedicine, 5433-5443.
[44] Hersh, J., Yang, Y. P., Roberts, E., Bilbao, D., Tao, W., Pollack, A., Daunert, S., Deo, S. K. (2023) Targeted bioluminescent imaging of pancreatic ductal adenocarcinoma using nanocarrier-complexed EGFR-binding affibody – Gaussia luciferase fusion protein. Pharmaceutics, 15(7), 1976.
[45] Wang, Y., Li, J., Li, X., Shi, J., Jiang, Z., Zhang, C. Y. (2022) Graphene-based nanomaterials for cancer therapy and anti-infections. Bioactive Materials, 14, 335-349.
[46] Asadi, M., Ghorbani, S. H., Mahdavian, L., Aghamohammadi, M. (2024) Graphene-based hybrid composites for cancer diagnostic and therapy. Journal of Translational Medicine, 22(1), 611.
[47] Huang, L., Zhang, Y., Li, Y., Meng, F., Li, H., Zhang, H., Tu, J., Sun, C., Luo, L. (2021) Time-programmed delivery of sorafenib and anti-CD47 antibody via a double-layer-gel matrix for postsurgical treatment of breast cancer. Nano-Micro Letters, 13(1), 141.
[48] Bai, X., Dong, C., Shao, X., Rahman, F. U., Hao, H., Zhang, Y. (2024) Research progress of fullerenes and their derivatives in the field of PDT. European Journal of Medicinal Chemistry, 271, 116398.
[49] Alfei, S., Reggio, C., Zuccari, G. (2025) Carbon nanotubes as excellent adjuvants for anticancer therapeutics and cancer diagnosis: a plethora of laboratory studies versus few clinical trials. Cells, 14(14), 1052.
[50] Alhashmi Alamer, F., Almalki, G. A. (2022) Fabrication of conductive fabrics based on SWCNTs, MWCNTs and graphene and their applications: a review. Polymers, 14(24), 5376.
[51] Wang, X., Gong, Z., Wang, T., Law, J., Chen, X., Wanggou, S., Wang, J., Ying, B., Francisco, M., Dong, W., Xiong, Y., Fan, J. J., MacLeod, G., Angers, S., Li, X., Dirks, P. B., Liu, X., Huang, X., Sun, Y. (2023) Mechanical nanosurgery of chemoresistant glioblastoma using magnetically controlled carbon nanotubes. Science Advances, 9(13), eade5321.
[52] Dockery, L. T., Daniel, M. C. (2023) Targeted doxorubicin-loaded dendronized gold nanoparticles. Pharmaceutics, 15(8), 2103.
[53] Hong, L., Xu, K., Yang, M., Zhu, L., Chen, C., Xu, L., Zhu, W., Jin, L., Wang, L., Lin, J., Wang, J., Ren, W., Wu, A. (2024) VISTA antibody-loaded Fe3O4@TiO2 nanoparticles for sonodynamic therapy-synergistic immune checkpoint therapy of pancreatic cancer. Materials Today Bio, 26, 101106.
[54] Kinnear, C., Moore, T. L., Rodriguez-Lorenzo, L., Rothen-Rutishauser, B., Petri-Fink, A. (2017) Form follows function: nanoparticle shape and its implications for nanomedicine. Chemical Reviews, 117(17), 11476-11521.
[55] Wu, J. (2021) The enhanced permeability and retention (EPR) effect: the significance of the concept and methods to enhance its application. Journal of Personalized Medicine, 11(8), 771.
[56] Blanco, E., Shen, H., Ferrari, M. (2015) Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nature Biotechnology, 33(9), 941-951.
[57] Mitchell, M. J., Billingsley, M. M., Haley, R. M., Wechsler, M. E., Peppas, N. A., Langer, R. (2021) Engineering precision nanoparticles for drug delivery. Nature Reviews Drug Discovery, 20(2), 101-124.
[58] Brenner, J. S., Mitragotri, S., Muzykantov, V. R. (2021) Red blood cell hitchhiking: a novel approach for vascular delivery of nanocarriers. Annual Review of Biomedical Engineering, 23(1), 225-248.
[59] Baoukina, S., Rozmanov, D., Tieleman, D. P. (2017) Composition fluctuations in lipid bilayers. Biophysical Journal, 113(12), 2750-2761.
[60] Ren, B., Li, H. M., Zhang, J. Y., Wang, J., Yang, Y., Ye, L. T., Yu, J., Xu, J., Quan, G., Li, J., Choon, W. C. (2026) A GPC1-Targeting Multifunctional Nanoplatform Combining Paclitaxel-Mediated Chemotherapy and Chlorin e6-Assisted Sonodynamic Therapy for Pancreatic Ductal Adenocarcinoma (PDAC) Treatment. Cancer Treatment and Research Communications, 101139.
[61] Li, Y., Chen, W., Kang, Y., Zhen, X., Zhou, Z., Liu, C., Chen, S., Huang, X., Liu, H. J., Koo, S., Kong, N., Ji, X., Xie, T., Tao, W. (2023) Nanosensitizer-mediated augmentation of sonodynamic therapy efficacy and antitumor immunity. Nature Communications, 14(1), 6973.
[62] Ahmed, A., Sarwar, S., Hu, Y., Munir, M. U., Nisar, M. F., Ikram, F., Asif, A., Rahman, S. U., Chaudhry, A. A., Rehman, I. U. (2021) Surface-modified polymeric nanoparticles for drug delivery to cancer cells. Expert Opinion on Drug Delivery, 18(1), 1-24.
[63] Palanikumar, L., Al-Hosani, S., Kalmouni, M., Nguyen, V. P., Ali, L., Pasricha, R., Barrera, F. N., Magzoub, M. (2020) pH-responsive high stability polymeric nanoparticles for targeted delivery of anticancer therapeutics. Communications Biology, 3(1), 95.
[64] Tang, Y., Cao, Y. (2020) Modeling the dynamics of antibody-target binding in living tumors. Scientific Reports, 10(1), 16764.
[65] Zelepukin, I. V., Shevchenko, K. G., Deyev, S. M. (2024) Rediscovery of mononuclear phagocyte system blockade for nanoparticle drug delivery. Nature Communications, 15(1), 4366.
[66] Piscatelli, J. A., Ban, J., Lucas, A. T., Zamboni, W. C. (2021) Complex factors and challenges that affect the pharmacology, safety and efficacy of nanocarrier drug delivery systems. Pharmaceutics, 13(1), 114.
[67] Beach, M. A., Nayanathara, U., Gao, Y., Zhang, C., Xiong, Y., Wang, Y., Such, G. K. (2024) Polymeric nanoparticles for drug delivery. Chemical Reviews, 124(9), 5505-5616.
[68] Donahue, N. D., Acar, H., Wilhelm, S. (2019) Concepts of nanoparticle cellular uptake, intracellular trafficking, and kinetics in nanomedicine. Advanced Drug Delivery Reviews, 143, 68-96.
[69] Kalli, M., Poskus, M. D., Stylianopoulos, T., Zervantonakis, I. K. (2023) Beyond matrix stiffness: targeting force-induced cancer drug resistance. Trends in Cancer, 9(11), 937-954.
[70] Tao, J., Yang, G., Zhou, W., Qiu, J., Chen, G., Luo, W., Zhao, F., You, L., Zheng, L., Zhang, T., Zhao, Y. (2021) Targeting hypoxic tumor microenvironment in pancreatic cancer. Journal of Hematology & Oncology, 14(1), 14.
[71] Kennel, K. B., Bozlar, M., De Valk, A. F., Greten, F. R. (2023) Cancer-associated fibroblasts in inflammation and antitumor immunity. Clinical Cancer Research, 29(6), 1009-1016.
Share and Cite
Ren, B., Yang, Y., Gan, Y., Wu, J., Wong, C. (2026) Multifunctional Antibody-drug-nanoparticle Conjugates for precision Cancer Therapy. Journal of Disease and Public Health, 2(1), 22-34. https://doi.org/10.71052/jdph/LLLX6280