Nanotechnology-Based Targeted Drug Delivery in Cancer: Recent Advances, Challenges and Future Perspectives

Abstract

Cancer is one of the major causes of morbidity and mortality worldwide. Conventional cancer treatments such as chemotherapy, radiotherapy and surgery are associated with several limitations, including poor drug specificity, systemic toxicity, inadequate drug concentration at the tumor site and development of drug resistance. Nanotechnology-based drug delivery systems have emerged as promising approaches for improving the therapeutic efficacy and safety of anticancer agents. Nanocarriers can improve drug solubility, stability, circulation time and bioavailability while facilitating targeted and controlled drug delivery. Various nanocarriers, including liposomes, polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, polymeric micelles, dendrimers, nanoemulsions and inorganic nanoparticles, have been investigated for cancer treatment. Nanotechnology also enables active targeting through ligands such as antibodies, peptides and folic acid, as well as stimulus-responsive drug release in response to changes in pH, temperature, enzymes or redox conditions. Several nanomedicines have progressed from laboratory research to clinical applications. However, challenges related to toxicity, manufacturing, reproducibility, stability, tumor heterogeneity and regulatory approval remain. This review discusses the principles, types, mechanisms, applications, advantages, limitations and future perspectives of nanotechnology-based drug delivery systems for cancer therapy.

Introduction

Cancer remains a major global public health challenge due to its increasing incidence, population ageing, and lifestyle and environmental factors. Despite advances in diagnosis and treatment, conventional cancer therapies are often limited by toxicity to healthy cells, poor drug solubility, unfavorable pharmacokinetics, inadequate tumor accumulation, and multidrug resistance. These challenges highlight the need for safer and more effective therapeutic approaches.

Targeted drug delivery aims to deliver anticancer drugs preferentially to cancer cells or tumor tissues while minimizing exposure to healthy tissues. It offers potential benefits, including reduced systemic toxicity, improved therapeutic efficacy, enhanced drug bioavailability, protection against premature drug degradation, controlled drug release, and improved management of drug resistance. However, the effectiveness of these systems depends on the drug, formulation, and characteristics of the tumor.

Nanotechnology plays an important role in advancing targeted cancer therapy by using nanoparticles to improve drug delivery and therapeutic performance. Nanoparticles can achieve passive targeting through the enhanced permeability and retention (EPR) effect or active targeting through ligands such as antibodies, peptides, aptamers, and folic acid. They can also support sustained drug release, combination therapy, improved intracellular delivery, and theranostic applications that integrate diagnosis and treatment. Nevertheless, tumor accumulation and penetration vary according to nanoparticle properties, tumor biology, and patient characteristics.

Nanoparticles are colloidal drug-delivery systems commonly ranging from approximately 1 to 1000 nm. Their high surface-area-to-volume ratio, tunable surface properties, and ability to encapsulate or associate with therapeutic agents make them promising carriers for anticancer drugs. Their performance depends on several physicochemical properties, including particle size, size distribution, surface charge, shape, surface area, drug-loading capacity, encapsulation efficiency, hydrophobicity, stability, drug-release profile, biocompatibility, and biodegradability. Careful optimization of these properties is essential for achieving effective and safe drug delivery.

Liposomes are one of the important nanocarriers used in cancer therapy. They are spherical vesicles primarily composed of phospholipid bilayers and can carry both hydrophilic and lipophilic drugs. Their structure consists of a phospholipid bilayer, an aqueous core, and, in many formulations, cholesterol to improve membrane stability. Surface modifiers such as polyethylene glycol (PEG) may also be incorporated to prolong circulation time. Liposomes can modify drug distribution and pharmacokinetics and may reduce the toxicity of certain anticancer agents.

In conclusion, nanotechnology-based drug delivery systems offer promising strategies for addressing the limitations of conventional cancer therapy. By improving drug delivery, modifying pharmacokinetics, and potentially reducing toxicity and drug resistance, these systems may enhance cancer treatment outcomes. However, their clinical success depends on formulation optimization, tumor-specific delivery, safety, and demonstrated therapeutic effectiveness.

Conclusion

Nanotechnology-based drug delivery systems represent an important advancement in cancer therapy. Nanocarriers can improve the solubility, stability, pharmacokinetic properties, and controlled release of anticancer drugs while providing opportunities for targeted delivery (Mitchell et al., 2021; Wicki et al., 2015). Liposomes, polymeric nanoparticles, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), micelles, dendrimers, nanoemulsions, and inorganic nanoparticles have demonstrated significant potential in preclinical and clinical research (Shi et al., 2017; Anselmo & Mitragotri, 2019). Nevertheless, biological variability, toxicity, manufacturing complexity, and regulatory challenges continue to limit their widespread application (Agrahari & Agrahari, 2018; Hua & de Matos, 2024). Continued research combining nanotechnology with targeted therapy, immunotherapy, gene therapy, and personalized medicine may contribute to safer and more effective cancer treatment (Shi et al., 2017; Wicki et al., 2015)..

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. https://doi.org/10.3322/caac.21834 [2] Shi, J., Kantoff, P. W., Wooster, R., & Farokhzad, O. C. (2017). Cancer nanomedicine: Progress, challenges and opportunities. Nature Reviews Cancer, 17(1), 20–37. https://doi.org/10.1038/nrc.2016.108 [3] Holohan, C., Van Schaeybroeck, S., Longley, D. B., & Johnston, P. G. (2013). Cancer drug resistance: An evolving paradigm. Nature Reviews Cancer, 13(10), 714–726. https://doi.org/10.1038/nrc3599 [4] Bhatia, S. N., Chen, X., Dobrovolskaia, M. A., & Lammers, T. (2022). Cancer nanomedicine. Nature Reviews Cancer, 22, 550–556. https://doi.org/10.1038/s41568-022-00496-9 [5] Peer, D., Karp, J. M., Hong, S., Farokhzad, O. C., Margalit, R., & Langer, R. (2007). Nanocarriers as an emerging platform for cancer therapy. Nature Nanotechnology, 2, 751–760. https://doi.org/10.1038/nnano.2007. [6] 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. https://doi.org/10.1038/s41573-020-0090-8 [7] Wicki, A., Witzigmann, D., Balasubramanian, V., & Huwyler, J. (2015). Nanomedicine in cancer therapy: Challenges, opportunities, and clinical applications. Journal of Controlled Release, 200, 138–157. https://doi.org/10.1016/j.jconrel.2014.12.030 [8] Blanco, E., Shen, H., & Ferrari, M. (2015). Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nature Biotechnology, 33(9), 941–951. https://doi.org/10.1038/nbt.3330 [9] Wilhelm, S., Tavares, A. J., Dai, Q., Ohta, S., Audet, J., Dvorak, H. F., & Chan, W. C. W. (2016). Analysis of nanoparticle delivery to tumours. Nature Reviews Materials, 1, Article 16014. https://doi.org/10.1038/natrevmats.2016.14 [10] Prasad, P., Gordijo, C. R., Abbasi, A. Z., Maeda, A., Ip, A., Rauth, A. M., DaCosta, R. S., & Wu, X. Y. (2014). Multifunctional albumin–MnO? nanoparticles modulate solid tumor microenvironment by attenuating hypoxia, acidosis, and interstitial fluid pressure for enhanced chemotherapy. ACS Nano, 8(4), 3202–3212. https://doi.org/10.1021/nn405773r [11] Mi, P. (2020). Stimuli-responsive nanocarriers for drug delivery, tumor imaging, therapy and theranostics. Theranostics, 10(10), 4557–4588. https://doi.org/10.7150/thno.38069 [12] Monopoli, M. P., Åberg, C., Salvati, A., & Dawson, K. A. (2012). Biomolecular coronas provide the biological identity of nanosized materials. Nature Nanotechnology, 7, 779–786. https://doi.org/10.1038/nnano.2012.207 [13] Nel, A. E., Mädler, L., Velegol, D., Xia, T., Hoek, E. M. V., Somasundaran, P., Klaessig, F., Castranova, V., & Thompson, M. (2009). Understanding biophysicochemical interactions at the nano–bio interface. Nature Materials, 8, 543–557. https://doi.org/10.1038/nmat2442 [14] Anselmo, A. C., & Mitragotri, S. (2019). Nanoparticles in the clinic: An update. Bioengineering & Translational Medicine, 4(3), Article e10143. https://doi.org/10.1002/btm2.10143 [15] Danaei, M., Dehghankhold, M., Ataei, S., Hasanzadeh Davarani, F., Javanmard, R., Dokhani, A., Khorasani, S., & Mozafari, M. R. (2018). Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics, 10(2), Article 57. https://doi.org/10.3390/pharmaceutics10020057 [16] Allen, T. M., & Cullis, P. R. (2013). Liposomal drug delivery systems: From concept to clinical applications. Advanced Drug Delivery Reviews, 65(1), 36–48. https://doi.org/10.1016/j.addr.2012.09.037?? [17] Bulbake, U., Doppalapudi, S., Kommineni, N., & Khan, W. (2017). Liposomal formulations in clinical use: An updated review. Pharmaceutics, 9(2), Article 12. https://doi.org/10.3390/pharmaceutics9020012?? [18] Bozzuto, G., & Molinari, A. (2015). Liposomes as nanomedical devices. International Journal of Nanomedicine, 10, 975–999. https://doi.org/10.2147/IJN.S68861?? [19] Pattni, B. S., & Torchilin, V. P. (2015). Endocytosis of nanomedicines. Journal of Controlled Release, 216, 23–34. https://doi.org/10.1016/j.jconrel.2015.07.006?? [20] Danhier, F., Ansorena, E., Silva, J. M., Coco, R., Le Breton, A., & Préat, V. (2012). PLGA-based nanoparticles: An overview of biomedical applications. Journal of Controlled Release, 161(2), 505–522. .https://doi.org/10.1016/j.jconrel.2012.01.043?? [21] Kamaly, N., Yameen, B., Wu, J., & Farokhzad, O. C. (2016). Degradable controlled-relSercombe, Lease polymers and polymeric nanoparticles: Mechanisms of controlling drug release. Chemical Reviews, 116(4), 2602–2663. https://doi.org/10.1021/acs.chemrev.5b00346?? [22] Duncan, R. (2003). The dawning era of polymer therapeutics. Nature Reviews Drug Discovery, 2(5), 347–360. https://doi.org/10.1038/nrd1088?? [23] Kumari, A., Yadav, S. K., & Yadav, S. C. (2010). Biodegradable polymeric nanoparticles based drug delivery systems. Colloids and Surfaces B: Biointerfaces, 75(1), 1–18. https://doi.org/10.1016/j.colsurfb.2009.09.001?? [24] Svenson, S., & Tomalia, D. A. (2005). Dendrimers in biomedical applications—Reflections on the field. Advanced Drug Delivery Reviews, 57(15), 2106–2129.https://doi.org/10.1016/j.addr.2005.09.018?? [25] 25.Esfand, R., & Tomalia, D. A. (2001). Poly(amidoamine) (PAMAM) dendrimers: From biomimicry to drug delivery and biomedical applications. Drug Discovery Today, 6(8), 427–436. [26] https://doi.org/10.1016/S1359-6446(01)01757-3?? [27] 26.Mintzer, M. A., & Grinstaff, M. W. (2011). Biomedical applications of dendrimers: A tutorial. Chemical Society Reviews, 40(1), 173–190. https://doi.org/10.1039/B901839P?? [28] Caminade, A.-M., Turrin, C.-O., Laurent, R., Ouali, A., & Delavaux-Nicot, B. (Eds.). (2011). Dendrimers: Towards catalytic, material and biomedical uses. Wiley. https://doi.org/10.1002/9780470977350?? [29] Mignani, S., El Kazzouli, S., Bousmina, M., & Majoral, J.-P. (2013). Expand classical drug administration ways by emerging routes using dendrimer drug delivery systems: A concise overview. Advanced Drug Delivery Reviews, 65(10), 1316–1330. https://doi.org/10.1016/j.addr.2013.01.001 [30] Beloqui, A., Solinís, M. Á., Rodríguez-Gascón, A., Almeida, A. J., & Préat, V. (2016). Nanostructured lipid carriers: Promising drug delivery systems for future clinics. Nanomedicine: Nanotechnology, Biology and Medicine, 12(1), 143–161. https://doi.org/10.1016/j.nano.2015.09.004?? [31] Wong, H. L., Bendayan, R., Rauth, A. M., Li, Y., & Wu, X. Y. (2007). Chemotherapy with anticancer drugs encapsulated in solid lipid nanoparticles. Advanced Drug Delivery Reviews, 59(6), 491–504. https://doi.org/10.1016/j.addr.2007.04.008?? [32] Dykman, L. A., & Khlebtsov, N. G. (2012). Gold nanoparticles in biology and medicine: Recent advances and prospects. Acta Naturae, 4(2), 24–33. https://doi.org/10.32607/20758251-2012-4-2-24-33?? [33] Colombo, M., Carregal-Romero, S., Casula, M. F., Gutiérrez, L., Morales, M. P., Böhm, I. B., Heverhagen, J. T., Prosperi, D., & Parak, W. J. (2012). Biological applications of magnetic nanoparticles. Chemical Society Reviews, 41(11), 4306–4334. https://doi.org/10.1039/C2CS15337H?? [34] Mamaeva, V., Sahlgren, C., & Lindén, M. (2013). Mesoporous silica nanoparticles in medicine—Recent advances. Advanced Drug Delivery Reviews, 65(5), 689–702. https://doi.org/10.1016/j.addr.2012.07.018?? [35] Gupta, A., Eral, H. B., Hatton, T. A., & Doyle, P. S. (2016). Nanoemulsions: Formation, properties and applications. Soft Matter, 12, 2826–2841. https://doi.org/10.1039/C5SM02958A?? [36] Solans, C., Izquierdo, P., Nolla, J., Azemar, N., & Garcia-Celma, M. J. (2005). Nano-emulsions. Current Opinion in Colloid & Interface Science, 10(3–4), 102–110. https://doi.org/10.1016/j.cocis.2005.06.004?? [37] Barenholz, Y. (2012). Doxil®—The first FDA-approved nano-drug: Lessons learned. Journal of Controlled Release, 160(2), 117–134. https://doi.org/10.1016/j.jconrel.2012.03.020?? [38] Paranjpe, M., & Müller-Goymann, C. C. (2014). Nanoparticle-mediated pulmonary drug delivery: A review. International Journal of Molecular Sciences, 15(4), 5852–5873. https://doi.org/10.3390/ijms15045852?? [39] Saraiva, C., Praça, C., Ferreira, R., Santos, T., Ferreira, L., & Bernardino, L. (2016). Nanoparticle-mediated brain drug delivery: Overcoming blood–brain barrier to treat neurodegenerative diseases. Journal of Controlled Release, 235, 34–47. https://doi.org/10.1016/j.jconrel.2016.05.044?? [40] Pridgen, E. M., Alexis, F., Kuo, T. T., Levy-Nissenbaum, E., Karnik, R., Blumberg, R. S., Langer, R., & Farokhzad, O. C. (2013). Transepithelial transport of Fc-targeted nanoparticles by the neonatal Fc receptor for oral delivery. Science Translational Medicine, 5(213), Article 213ra167. https://doi.org/10.1126/scitranslmed.3007049??

Copyright

Copyright © 2026 Pratiksha A. Kodalkar , Megha B. Borkar , Mrs. S. V. Kodalkar , Dr. Nagaraju Potnuri . This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.