Nanoparticle-Based Drug Delivery Systems in Cancer Therapy: A Comprehensive Review

Abstract

Cancer continues to be a major global health issue with high mortality rates due to limitations of conventional chemotherapy, such as non specific drug distribution and systemic toxicity. Nanoparticle based drug delivery systems offer promise for improved cancer therapy by enabling targeted delivery, controlled drug release, and enhanced bioavailability. This review critically examines various nanocarrier platforms, including liposomes, polymeric nanoparticles, solid lipid nanoparticles, and metallic nanoparticles. Mechanisms of both passive and active targeting, advantages, clinical applications, limitations, and regulatory challenges are discussed. Recent developments from 2020–2025, such as biomimetic and stimuli responsive nanocarriers, are also evaluated. Prospects for future research and clinical translation are highlighted.

Keywords

Introduction

Cancer is defined by uncontrolled cell proliferation and the potential to invade adjacent tissues and metastasize to distant organs. Conventional chemotherapy remains a frontline treatment strategy; however, its effectiveness is often compromised by systemic toxicity, poor selectivity, and the development of multidrug resistance. These limitations underscore the need for more effective and safer drug delivery methods.

Nanotechnology has revolutionized the field of drug delivery by enabling nanoscale carriers that improve drug solubility, prolong circulation time, and facilitate targeted delivery to tumor tissues. Nanoparticles, typically 1–100 nm in diameter, exhibit unique physicochemical properties, including high surface?to?volume ratio and modifiable surface chemistry, which improve tumor targeting via enhanced permeability and retention (EPR) and functional ligand attachment.

2. Types of Nanoparticles

2.1 Liposomes

Liposomes are phospholipid vesicles capable of carrying both hydrophilic and hydrophobic drugs. Liposomal formulations such as Doxil® have significantly reduced cardiotoxicity compared to free drugs.

2.2 Polymeric Nanoparticles

These nanoparticles are fabricated from biodegradable polymers such as PLGA, providing controlled drug release and protecting encapsulated agents from degradation.

2.3 Solid Lipid Nanoparticles (SLNs)

SLNs combine the stability of polymeric nanoparticles with high drug loading capacity, offering controlled drug release and improved stability over traditional systems.

2.4 Metallic Nanoparticles

Gold and silver nanoparticles possess unique optical and electronic properties used in imaging, diagnostics, and photothermal therapies.

3. Mechanisms of Drug Targeting

3.1 Passive Targeting (EPR Effect)

Passive targeting leverages the Enhanced Permeability and Retention effect, where nanoparticles accumulate preferentially in tumor tissue due to leaky vasculature and deficient lymphatic drainage.

3.2 Active Targeting

Active targeting involves functionalizing nanoparticle surfaces with ligands such as antibodies, peptides, or aptamers, which bind selectively to receptors overexpressed on cancer cells.

4. Advantages of Nanoparticle?Based Systems

Nanoparticle?mediated delivery offers several benefits over conventional chemotherapy, including:
? Enhanced tumor targeting
? Reduced systemic toxicity
? Improved bioavailability
? Controlled and sustained drug release
? Enhanced pharmacokinetics

5. Applications in Cancer Therapy

Nanoparticle systems have shown promise in both clinical and experimental settings. Examples include:
? Liposomal Doxorubicin (Doxil®): Reduced cardiac toxicity and improved targeting
? Albumin?bound Paclitaxel (Abraxane®): Enhanced solubility and tumor uptake
? Lipid nanoparticles (LNPs): Widely used in gene delivery and immunotherapy

Recent studies (2023–2025) focus on:
? Stimuli?responsive nanoparticles
? Biomimetic nanocarriers (cell membrane?coated)
? Exosome?based delivery systems

Lipid?based systems dominate due to favorable safety and delivery efficiency.

6. Limitations and Challenges

6.1 Toxicity Concerns

Accumulation of nanoparticles in organs such as liver and spleen can cause long?term toxicity and unpredictable biological interactions.

6.2 Biological Barriers

Tumor heterogeneity and the presence of physiological barriers restrict effective nanoparticle penetration.

6.3 Manufacturing Challenges

High production costs, difficulties in scale?up, and batch variability hinder commercialization.

6.4 Regulatory Challenges

Regulatory authorities (FDA, EMA) require comprehensive evaluation of pharmacokinetics, toxicity, and reproducibility. The lack of standardized regulatory criteria for nanomedicines remains a significant obstacle.

7. Future Perspectives

Future research is steering toward:
? Smart and stimuli?responsive nanoparticles
? Personalized nanomedicine
? Multifunctional combination therapies
? AI?assisted nanocarrier design

CONCLUSION

Nanoparticle?based drug delivery systems hold transformative potential in cancer therapy by enabling targeted treatment, improved efficacy, and reduced toxicity. Continued advancements in nanocarrier design and regulatory frameworks are essential to realize widespread clinical adoption.

Declarations

Funding: None

Conflict of interest: None declared

Ethics approval: Not applicable (review article)

Consent to participate: Not applicable

Consent to publish: All authors consent to publication

REFERENCES

1. Allen TM, Cullis PR. Drug delivery systems: entering the mainstream. Science. 2004;303(5665):1818–1822.
2. Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, Langer R. Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol. 2007;2(12):751–760.
3. Torchilin VP. Multifunctional, stimuli?sensitive nanoparticulate systems for drug delivery. Nat Rev Drug Discov. 2014;13(11):813–827.
4.  Brannon?Peppas L, Blanchette JO. Nanoparticle and targeted systems for cancer therapy. Adv Drug Deliv Rev. 2012;64:206–212.
5. Duncan R. Polymer conjugates as anticancer nanomedicines. Nat Rev Cancer. 2006;6:688–701.
6. Farokhzad OC, Langer R. Impact of nanotechnology on drug delivery. ACS Nano. 2009;3(1):16–20.
7. Jain RK. Delivery of molecular and cellular medicine to solid tumors. Science. 1996;271(5257):1079–1080.
8. Maeda H, Wu J, Sawa T, Matsumura Y, Hori K. Tumor vascular permeability and the EPR effect in macromolecular therapeutics. J Control Release. 2000;65(1–2):271–284.
9. Wang B, Wang Y, Guan H, Zhang W. Next?generation lipid nanoparticles for targeted cancer therapy. Signal Transduct Target Ther. 2024;9:27.
10. Liu Y, Chen X, Zhang A. Recent advances in polymeric nanoparticles for cancer drug delivery. Int J Pharm. 2024;612:122339.
11. Desai N, Trieu V, Damascelli B, Mortimer J. Increased efficacy and reduced toxicity: nanoparticle albumin?bound paclitaxel in cancer therapy. Nanomedicine. 2025;30:102345.
12. Zhang L, Gu FX, Chan JM, Wang AZ, Langer RS, Farokhzad OC. Nanoparticles in medicine: therapeutic applications and developments. Clin Pharmacol Ther. 2008;83(5):761–769.
13. Blanco E, Shen H, Ferrari M. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat Biotechnol. 2015;33:941–951.
14. Wilhelm S, Tavares AJ, Dai Q, et al. Analysis of nanoparticle delivery to tumors. Nat Rev Mater. 2016;1:16014.
15. Blanco E, Bey EA, Khemtong C, Yang SG, Kessinger CW, Sumer BD, Gao J. Nanomedicine in cancer therapy: targeted drug delivery and imaging. Pharm Res. 2011;28(2):187–199.
16. Petros RA, DeSimone JM. Strategies in the design of nanoparticles for therapeutic applications. Nat Rev Drug Discov. 2010;9(8):615–627.
17. Shi J, Kantoff PW, Wooster R, Farokhzad OC. Cancer nanomedicine: progress, challenges and opportunities. Nat Rev Cancer. 2017;17(1):20–37.
18. Sanna V, Pala N, Sechi M. Targeted therapy using nanotechnology: focus on cancer. Int J Nanomedicine. 2014;9:467–483.
19. Verma A, Stellacci F. Effect of surface properties on nanoparticle–cell interactions. Small. 2010;6(1):12–21.
20. Alexis F, Pridgen E, Molnar LK, Farokhzad OC. Factors affecting the clearance and biodistribution of polymeric nanoparticles. Mol Pharm. 2008;5(4):505–515.
21. Zhang Q, Liu H, Wu F, et al. Enhanced delivery of chemotherapeutic agents using nanoparticle carriers in cancer therapy. J Biomed Nanotechnol. 2023;19:159–176.