journal article·2026-02

PEGylated dendrimers for precision cancer therapy: Advances in tumor targeting, drug delivery, and clinical translation

Prashant Kesharwani, Vivek Puri, Taha Alqahtani, Humood Al Shmrany, Garima Gupta, Khang Wen Goh, Amirhossein Sahebkar

Publisher page

Abstract

PEGylated dendrimers have emerged as highly adaptable nanocarriers for targeted cancer therapy, offering exceptional control over size, surface functionality, and drug loading. The covalent attachment of polyethylene glycol (PEG) chains to dendrimer surfaces improves biocompatibility, enhances circulation time, and minimizes immune clearance, facilitating passive tumor targeting through the enhanced permeability and retention (EPR) effect. These engineered nanosystems allow for precise encapsulation or conjugation of chemotherapeutic agents, nucleic acids, and imaging probes, with tunable release profiles. Functionalization with tumor-specific ligands further enables active targeting, improving cellular uptake and minimizing systemic toxicity. Preclinical studies have demonstrated the efficacy of PEGylated dendrimers in delivering anticancer payloads across various malignancies including breast, brain, liver, and lung cancers while reducing off-target effects. Their combinatorial use with gene therapy, immunotherapy, or photothermal agents further enhances therapeutic outcomes. This review discusses the structural design, functional modifications, and translational progress of PEGylated dendrimers, highlighting their potential as next-generation platforms for personalized and clinically relevant cancer nanomedicine.
Source: europepmc · Quality: candidate unverified · Source record ↗

Research context

OpenAlex topics: Dendrimers and Hyperbranched Polymers · RNA Interference and Gene Delivery · Advanced biosensing and bioanalysis techniques

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

References (100+)

Show source-provided references
1. Carbon Nanotubes (CNTs)
2. An overview of cancer biology, pathophysiological development and it’s treatment modalities: current challenges of cancer anti-angiogenic therapy10.1080/07357907.2024.2361295 ↗
3. Rnai-combined nano-chemotherapeutics to tackle resistant tumors10.1016/j.drudis.2016.06.029 ↗
4. A review on dendrimer-based nanoconjugates and their intracellular trafficking in cancer photodynamic therapy10.1080/21691401.2024.2368033 ↗
5. Dendrimer as nanocarrier for drug delivery and drug targeting therapeutics: A fundamental to advanced systematic review10.1080/00914037.2022.2158334 ↗
6. Capsaicin-loaded alginate nanoparticles embedded polycaprolactone-chitosan nanofibers as a controlled drug delivery nanoplatform for anticancer activity10.1016/j.jcis.2023.01.139 ↗
7. Recent advances and prospects in gemcitabine drug delivery systems
8. The emerging role of immune checkpoint inhibitors in the treatment of triple-negative breast cancer10.1016/j.drudis.2021.03.011 ↗
9. Rnai-combined nano-chemotherapeutics to tackle resistant tumors10.1016/j.drudis.2016.06.029 ↗
10. Intranasal delivery of naloxone-loaded solid lipid nanoparticles as a promising simple and non-invasive approach for the management of opioid overdose10.1016/j.ijpharm.2021.120428 ↗
11. Carbon nanotubes as an emerging nanocarrier for the delivery of doxorubicin for improved chemotherapy10.1016/j.colsurfb.2021.112044 ↗
12. Nanotechnology-based siRNA delivery strategies for treatment of triple negative breast cancer10.1016/j.ijpharm.2021.120835 ↗
13. Update on therapeutic potential of emerging nanoformulations of phytocompounds in Alzheimer’s and Parkinson’s disease
14. Formulation and development of transferrin targeted solid lipid nanoparticles for breast Cancer therapy10.3389/fphar.2020.614290 ↗
15. Solubility enhancement and targeted delivery of a potent anticancer flavonoid analogue to cancer cells using ligand decorated dendrimer nano-architectures10.1016/j.jcis.2016.08.061 ↗
16. Fabrication and characterization of nifedipine loaded β-cyclodextrin nanosponges: an in vitro and in vivo evaluation10.1016/j.jddst.2017.08.005 ↗
17. Validating the anticancer potential of carbon nanotube-based therapeutics through cell line testing10.1016/j.drudis.2015.05.004 ↗
18. Synthesis and characterization of folate decorated albumin bio-conjugate nanoparticles loaded with a synthetic curcumin difluorinated analogue10.1016/j.jcis.2017.01.092 ↗
19. Evaluation of dendrimer safety and efficacy through cell line studies
20. Exploring dendrimer-based drug delivery systems and their potential applications in cancer immunotherapy10.1016/j.eurpolymj.2022.111471 ↗
21. Understanding the journey of biopolymeric nanoformulations for oral drug delivery: conventional to advanced treatment approaches10.1016/j.eurpolymj.2024.113338 ↗
22. Nanomaterials in the Wound Healing Process: New Insights and Advancements
23. A porous calcium-zirconia scaffolds composed of magnetic nanoparticles for bone cancer treatment: fabrication, characterization and FEM analysis10.1016/j.ceramint.2021.09.216 ↗
24. Review of the efficacy of nanoparticle-based drug delivery systems for cancer treatment10.1016/j.bmt.2023.09.001 ↗
25. Carrier Systems for Advanced Drug Delivery: Improving Drug Solubility/Bioavailability and Administration Routes
26. Dendrimer as nanocarrier for drug delivery10.1016/j.progpolymsci.2013.07.005 ↗
27. Cancer targeting potential of some ligand-anchored poly(propylene imine) dendrimers: a comparison10.1016/j.nano.2010.10.010 ↗
28. Recent advances in dendrimer-based nanovectors for tumor-targeted drug and gene delivery
29. PAMAM dendrimers as promising nanocarriers for RNAi therapeutics10.1016/j.mattod.2015.06.003 ↗
30. Generation dependent cancer targeting potential of poly(propyleneimine) dendrimer10.1016/j.biomaterials.2014.03.064 ↗
31. Dendrimer-entrapped gold nanoparticles as promising nanocarriers for anticancer therapeutics and imaging10.1016/j.pmatsci.2019.03.003 ↗
32. Surface-modified nintedanib-loaded solid lipid nanoparticles for effective targeting of non-small cell lung cancer10.1016/j.colsurfb.2025.114622 ↗
33. Gold nanoparticle-enabled doxorubicin delivery: advancing targeted chemotherapy in cancer therapy10.1016/j.inoche.2025.114467 ↗
34. Biomimetic nanoparticles: A revolutionary approach to breast cancer therapy using cell membrane coatings
35. Green biogenic silver nanoparticles, therapeutic uses, recent advances, risk assessment, challenges, and future perspectives
36. Dendrimer nanohybrid carrier systems: an expanding horizon for targeted drug and gene delivery10.1016/j.drudis.2017.06.009 ↗
37. Generation dependent safety and efficacy of folic acid conjugated dendrimer based anticancer drug formulations10.1007/s11095-014-1549-2 ↗
38. PAMAM dendrimer as a talented multifunctional biomimetic nanocarrier for cancer diagnosis and therapy10.1016/j.colsurfb.2021.111837 ↗
39. Dendrimer technologies for brain tumor10.1016/j.drudis.2016.02.006 ↗
40. Poly (propylene imine) dendrimer as an emerging polymeric nanocarrier for anticancer drug and gene delivery10.1016/j.eurpolymj.2021.110683 ↗
41. The effect of polyethylene glycol spacer chain length on the tumor-targeting potential of folate-modified PPI dendrimers10.1007/s11051-013-1625-2 ↗
42. Formulation development and in vitro-in vivo assessment of the fourth-generation PPI dendrimer as a cancer-targeting vector10.2217/nnm.13.210 ↗
43. Ligand anchored poly(propyleneimine) dendrimers for brain targeting: comparative in vitro and in vivo assessment10.1016/j.jcis.2016.07.047 ↗
44. Development of binary dispersions and nanocomposites of irbesartan with enhanced antihypertensive activity10.34172/bi.2020.34 ↗
45. Polymer–drug and polymer–protein conjugated nanocarriers: design, drug delivery, imaging, therapy, and clinical applications10.1002/wnan.1988 ↗
46. RGD engineered dendrimer nanotherapeutic as an emerging targeted approach in cancer therapy10.1016/j.jconrel.2021.10.028 ↗
47. Lyophilized mucoadhesive-dendrimer enclosed matrix tablet for extended oral delivery of albendazole10.1016/j.ejpb.2015.10.015 ↗
48. In vivo antitumor activity of folate-conjugated cholic acid-polyethylenimine micelles for the codelivery of doxorubicin and siRNA to colorectal adenocarcinomas10.1021/acs.molpharmaceut.5b00827 ↗
49. Nanoparticles in cancer theragnostic and drug delivery: A comprehensive review10.1016/j.lfs.2024.122899 ↗
50. Advances in dendritic systems and dendronized nanoparticles: paradigm shifts in cancer targeted therapy and diagnostics
51. Formulation and development of ACUPA-targeting PEGylated nanoliposomes for treatment of prostate cancer10.1016/j.tice.2025.102830 ↗
52. Advanced polymeric dendrimers in the management of Alzheimer’s disease10.1002/pat.6348 ↗
53. Research progress of disulfide bond based tumor microenvironment targeted drug delivery system10.2147/IJN.S471734 ↗
54. Nanodelivery in gene therapy
55. The global characterisation of a drug-dendrimer conjugate - PEGylated poly-lysine dendrimer10.1016/j.xphs.2022.11.005 ↗
56. Polyethylene glycol-mediated functionalization of nanodelivery systems for improving their pharmacokinetic profile and anticancer efficacy
57. Recent developments in synthetic approaches for macromolecular prodrugs10.1016/j.progpolymsci.2024.101855 ↗
58. Polyethylene glycol-mediated functionalization of nanodelivery systems for improving their pharmacokinetic profile and anticancer efficacy
59. The immune-stealth polymeric coating on drug delivery nanocarriers: in vitro engineering and in vivo fate10.1177/08853282231185352 ↗
60. Enhancing drug penetration in solid tumors via nanomedicine: evaluation models, strategies and perspectives
61. Aptamer grafted nanoparticle as targeted therapeutic tool for the treatment of breast cancer10.1016/j.biopha.2021.112530 ↗
62. Dendrimer generational nomenclature: the need to harmonize10.1016/j.drudis.2014.12.015 ↗
63. An insight into aptamer engineered dendrimer for cancer therapy10.1016/j.eurpolymj.2021.110746 ↗
64. Galactose engineered nanocarriers: hopes and hypes in cancer therapy10.1016/j.eurpolymj.2022.111759 ↗
65. Recent update of toxicity aspects of nanoparticulate systems for drug delivery10.1016/j.ejpb.2021.02.010 ↗
66. Dendrimer entrapped microsponge gel of dithranol for effective topical treatment10.1016/j.heliyon.2019.e01343 ↗
67. Lipid based nanocarriers system for topical delivery of photosensitizers10.1016/j.drudis.2017.04.010 ↗
68. Perspectives for improving the tumor targeting of nanomedicine via the EPR effect in clinical tumors10.3390/ijms241210082 ↗
69. Dendrimer-mediated targeting of angiogenic biomarkers: therapeutic intervention against cancer10.1080/17425247.2024.2394631 ↗
70. Targeted Therapeutic Strategies for the Treatment of Cancer10.3390/cancers16020461 ↗
71. Efficient PEGylated dendrimer nanoplatform for codelivery of hyaluronidase and methotrexate: a new frontier in chemotherapeutic efficacy and tumor penetration
72. PEGylated PAMAM dendrimers: enhancing efficacy and mitigating toxicity for effective anticancer drug and gene delivery10.1016/j.actbio.2016.07.015 ↗
73. Synthesize and characterization of a novel cadmium selenide nanoparticle with Iron precursor applicable in hyperthermia of Cancer cells
74. Advances in drug delivery-based therapeutic strategies for renal fibrosis treatment10.1039/D4TB00737A ↗
75. Advancements in dendrimer-based drug delivery for combinatorial cancer therapy
76. A comprehensive review on doxorubicin: mechanisms, toxicity, clinical trials, combination therapies and nanoformulations in breast cancer
77. Dendrimers as prospective nanocarrier for targeted delivery against lung cancer10.1016/j.eurpolymj.2022.111635 ↗
78. Recent advances in preclinical research using PAMAM dendrimers for cancer gene therapy10.3390/ijms22062912 ↗
79. Micro-Nanocarriers based drug delivery Technology for Blood-Brain Barrier Crossing and Brain Tumor Targeting Therapy
80. Targeted Nanocarrier-Based Drug Delivery Strategies for Improving the Therapeutic Efficacy of PARP Inhibitors against Ovarian Cancer10.3390/ijms25158304 ↗
81. Recent advances in targeted drug delivery strategy for enhancing oncotherapy10.3390/pharmaceutics15092233 ↗
82. Dendrimer: an update on recent developments and future opportunities for the brain tumors diagnosis and treatment10.3389/fphar.2023.1159131 ↗
83. Promising strategies for improving oral bioavailability of poor water-soluble drugs10.1080/17460441.2023.2211801 ↗
84. Impact of pegylation on biopharmaceutical properties of dendrimers10.1016/j.polymer.2014.12.051 ↗
85. Clinical diagonal translation of nanoparticles: case studies in dendrimer nanomedicine10.1016/j.jconrel.2021.07.036 ↗
86. Current update on nanoplatforms as therapeutic and diagnostic tools: a review for the materials used as nanotheranostics and imaging modalities
87. Dendrimers: advancements and potential applications in cancer diagnosis and treatment—an overview10.3390/pharmaceutics15051406 ↗
88. Dendrimers for cancer immunotherapy: avidity-based drug delivery vehicles for effective anti-tumor immune response10.1002/wnan.1752 ↗
89. Preclinical development of drug delivery systems for paclitaxel-based cancer chemotherapy10.1016/j.jconrel.2017.09.026 ↗
90. Engineered smart materials for RNA based molecular therapy to treat glioblastoma
91. Nanoparticle-assisted targeting of the tumour microenvironment10.1016/j.onano.2022.100097 ↗
92. Sustained and efficient porphyrin generation in vivo using dendrimer conjugates of 5-ALA for photodynamic therapy10.1016/j.jconrel.2009.01.002 ↗
93. Recent nanotheranostic approaches in cancer research10.1007/s10238-023-01262-3 ↗
94. Nanoparticle-mediated combination therapy: two-in-one approach for cancer10.3390/ijms19103264 ↗
95. Nanomedicine of synergistic drug combinations for cancer therapy – strategies and perspectives10.1016/j.jconrel.2016.06.012 ↗
96. Nanoparticle-based drug delivery systems targeting cancer cell surfaces10.1039/D3RA02969G ↗
97. Receptor-targeted nanocarriers for therapeutic delivery to cancer10.3109/09687688.2010.521200 ↗
98. Smart AS1411-aptamer conjugated pegylated PAMAM dendrimer for the superior delivery of camptothecin to colon adenocarcinoma in vitro and in vivo10.1016/j.ijpharm.2017.01.044 ↗
99. Synthesis and in vivo antitumor efficacy of PEGylated poly(l-lysine) dendrimer-camptothecin conjugates10.1021/mp9001206 ↗
100. PEGylated G4 dendrimers as a promising nanocarrier for piperlongumine delivery: synthesis, characterization, and anticancer activity10.1016/j.eurpolymj.2022.111547 ↗