Nano drugs in modern Drug delivery : "advances , application and economic challenges"
Subject Areas :Kiyana Ghasemi Ghasemvand 1 * , Atoosa Mohammadasgari 2
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Keywords: Nanoparticles, Nano Drug, Drug delivery, Cancer , Nano medicine,
Abstract :
Nanotechnology has been an influential advancement across all aspects of science, from mechanical technologies to medicine. One of these benefits and impacts is Nano drugs, which, by leveraging nanotechnology, have brought about a remarkable transformation in the diagnosis and treatment of cancer. These drugs, with features such as high surface-to-volume ratio, active and passive targeting, and responsiveness to tumor stimuli, enhance therapeutic efficacy and reduce side effects. In this article, I aimed to first examine the physicochemical principles and mechanisms of action of nanoparticles, including the enhanced permeability and retention (EPR) effect and molecular targeting. Then, clinically approved Nano drugs such as Doxil® and Abraxane® are analyzed in technical detail. Additionally, emerging technologies like smart multi-stimuli systems and CRISPR-Cas9-based gene editing are discussed. Economic challenges along with engineered solutions are presented, and finally, future prospects, including the integration of artificial intelligence and the development of theranostic systems, are outlined. This article provides a comprehensive review of the advancements in cancer Nano drugs, from basic principles to advanced clinical applications.
1. International Organization for Standardization. ISO/TS 80004-2:2015 Nanotechnologies - Vocabulary - Part 2: Nano-objects. Geneva: ISO; 2015. 32 p.
2. Jain PK, Huang X, El-Sayed IH, El-Sayed MA. Noble metals on the nanoscale: optical and photothermal properties and some applications in imaging, sensing, biology, and medicine. Acc Chem Res. 2008 Dec;41(12):1578-86. doi:10.1021/ar7002804
3. Kovalenko MV, et al. Prospects of nanoscience with nanocrystals. *ACS Nano*. 2022;16(1):30-43. doi:10.1021/acsnano.1c06583
4. Laleh Y, Pourmahdian S, Tehranchi MM. Synthesis of gold nanoparticles for biomedical applications. In: Proceedings of the 5th Iranian Biotechnology Conference; 2005 Nov 12-14; Tehran, Iran. p. 45-50.
5. Dreaden EC, Alkilany AM, Huang X, Murphy CJ, El-Sayed MA. The golden age: gold nanoparticles for biomedicine. Chem Soc Rev. 2012 Apr 7;41(7):2740-79. doi:10.1039/C1CS15237H
6. Danhier F, Ansorena E, Silva JM, Coco R, Le Breton A, Préat V. PLGA-based nanoparticles: an overview of biomedical applications. J Control Release. 2012 Jul 20;161(2):505-22. doi:10.1016/j.jconrel.2012.01.043
7. Sercombe L, Veerati T, Moheimani F, Wu SY, Sood AK, Hua S. Advances and challenges of liposome assisted drug delivery. Front Pharmacol. 2015 Dec 23;6:286. doi:10.3389/fphar.2015.00286
8. Suk JS, Xu Q, Kim N, Hanes J, Ensign LM. PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Adv Drug Deliv Rev. 2016 Apr 1;99(Pt A):28-51. doi:10.1016/j.addr.2015.09.012
9. Pourfallah TA. Nanohyperthermia: principles and clinical applications. Razi J Med Sci. 2018;25(3):1-15.
10. Heldin CH, Rubin K, Pietras K, Östman A. High interstitial fluid pressure - an obstacle in cancer therapy. Nat Rev Cancer. 2004 Oct;4(10):806-13. doi:10.1038/nrc1456
11. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001 Mar 15;344(11):783-92. doi:10.1056/NEJM200103153441101
12. Ruoslahti E. RGD and other recognition sequences for integrins. Annu Rev Cell Dev Biol. 1996;12:697-715. doi:10.1146/annurev.cellbio.12.1.697
13. Zhou J, Rossi J. Aptamers as targeted therapeutics: current potential and challenges. Nat Rev Drug Discov. 2017 Mar;16(3):181-202. doi:10.1038/nrd.2016.199
14.O'Brien MER, et al. Reduced cardiotoxicity with comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX™/Doxil®) versus conventional doxorubicin. *Ann Oncol*. 2004;15(3):440-9. doi:10.1093/annonc/mdh097
15. Mura S, Nicolas J, Couvreur P. Stimuli-responsive nanocarriers for drug delivery. Nat Mater. 2013 Nov;12(11):991-1003. doi:10.1038/nmat3776
16. Xu X, et al. Engineered nanocarriers for CRISPR-Cas9 genome editing. *Nat Rev Mater*. 2023;8(6):401-20. doi:10.1038/s41578-023-00558-w
17. Whitehead KA, Langer R, Anderson DG. Knocking down barriers: advances in siRNA delivery. Nat Rev Drug Discov. 2009 Feb;8(2):129-38. doi:10.1038/nrd2742
18. Salvati A, Pitek AS, Monopoli MP, Prapainop K, Bombelli FB, Hristov DR, et al. Transferrin-functionalized nanoparticles lose their targeting capabilities when a biomolecule corona adsorbs on the surface. Nat Nanotechnol. 2013 Feb;8(2):137-43. doi:10.1038/nnano.2012.237
19. Gref R, Lück M, Quellec P, Marchand M, Dellacherie E, Harnisch S, et al. 'Stealth' corona-core nanoparticles surface modified by polyethylene glycol (PEG): influences of the corona (PEG chain length and surface density) and of the core composition on phagocytic uptake and plasma protein adsorption. Colloids Surf B Biointerfaces. 2000 Oct 1;18(3-4):301-13. doi:10.1016/S0927-7765(99)00156-3
20. Valencia PM, Farokhzad OC, Karnik R, Langer R. Microfluidic technologies for accelerating the clinical translation of nanoparticles. Nat Nanotechnol. 2012 May 20;7(10):623-9. doi:10.1038/nnano.2012.168
21. Barenholz Y. Doxil® - the first FDA-approved nano-drug: lessons learned. J Control Release. 2012 Dec 10;160(2):117-34. doi:10.1016/j.jconrel.2012.03.020
22. Desai N, Trieu V, Yao Z, Louie L, Ci S, Yang A, et al. Increased antitumor activity, intratumor paclitaxel concentrations, and endothelial cell transport of cremophor-free, albumin-bound paclitaxel, ABI-007, compared with cremophor-based paclitaxel. Clin Cancer Res. 2006 Feb 1;12(3 Pt 1):1317-24. doi:10.1158/1078-0432.CCR-05-1634
23. Wang-Gillam A, Li CP, Bodoky G, Dean A, Shan YS, Jameson G, et al. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial. Lancet. 2016 Feb 6;387(10018):545-57. doi:10.1016/S0140-6736(15)00986-1
24. Oberli MA, Reichmuth AM, Dorkin JR, Mitchell MJ, Fenton OS, Jaklenec A, et al. Lipid nanoparticle assisted mRNA delivery for potent cancer immunotherapy. Nano Lett. 2017 Mar 8;17(3):1326-35. doi:10.1021/acs.nanolett.6b03329
25. Siepmann J, Peppas NA. Modeling of drug release from delivery systems based on hydroxypropyl methylcellulose (HPMC). Adv Drug Deliv Rev. 2001 Jun 11;48(2-3):139-57. doi:10.1016/S0169-409X(01)00112-0
26. Popović Z, Liu W, Chauhan VP, Lee J, Wong C, Greytak AB, et al. A nanoparticle size series for in vivo fluorescence imaging. Angew Chem Int Ed Engl. 2010 Oct 25;49(46):8649-52. doi:10.1002/anie.201003142
27. Lee ES, Na K, Bae YH. Super pH-sensitive multifunctional polymeric micelle. Nano Lett. 2005 Feb;5(2):325-9. doi:10.1021/nl0479987
28. Thurber GM, Schmidt MM, Wittrup KD. Antibody tumor penetration: transport opposed by systemic and antigen-mediated clearance. Adv Drug Deliv Rev. 2008 Mar 1;60(12):1421-34. doi:10.1016/j.addr.2008.04.012
29. Longmire M, Choyke PL, Kobayashi H. Clearance properties of nano-sized particles and molecules as imaging agents: considerations and caveats. Nanomedicine (Lond). 2008 Oct;3(5):703-17. doi:10.2217/17435889.3.5.703
30. Gabizon A, Shmeeda H, Barenholz Y. Pharmacokinetics of pegylated liposomal Doxorubicin: review of animal and human studies. Clin Pharmacokinet. 2003;42(5):419-36. doi:10.2165/00003088-200342050-00002
31. Desai N. Challenges in development of nanoparticle-based therapeutics. AAPS J. 2012 Jun;14(2):282-95. doi:10.1208/s12248-012-9339-4
32. Hou X, Zaks T, Langer R, Dong Y. Lipid nanoparticles for mRNA delivery. Nat Rev Mater. 2021 Dec;6(12):1078-94. doi:10.1038/s41578-021-00358-0
33. Borna News Agency. Annual report on cost-effectiveness of Iranian nanodrugs in insurance systems [Internet]. Tehran: Borna News; 2023 Mar 15 [cited 2025 Apr 1]. Available from: https://www.bornanews.ir/reports/nanodrugs2023
34. Iran Food and Drug Administration. Approval document of SinaDoxosome (Liposomal Doxorubicin). Tehran: FDA Iran; 2020. Report No.: IN-DF-2020-045.
35. Mehrali M. [Personal interview on molecular targeting in nanodrugs]. Tehran: Tehran University; 2025 Jan 10. Persian.
36. Nanotechnology Headquarters of Iran. Comparative pricing analysis of domestic vs. imported nanodrugs. Tehran: NTH; 2024. Report No.: NTH-RP-2024-03.
37. Source: ACS Nano. Regulatory challenges in nanomedicine approval. ACS Nano. 2023 Jan;17(1):1-3. doi:10.1021/acsnano.2c12345
38. Source: J Pharm Sci. Cost analysis of nanodrug clinical trials. J Pharm Sci. 2024 Feb;113(2):345-50. doi:10.1016/j.xphs.2023.11.012
39. Hashizume H, Baluk P, Morikawa S, McLean JW, Thurston G, Roberge S, et al. Openings between defective endothelial cells explain tumor vessel leakiness. Am J Pathol. 2000 Jun;156(4):1363-80. doi:10.1016/S0002-9440(10)65006-7
40. Walkey CD, Chan WC. Understanding and controlling the interaction of nanomaterials with proteins in a physiological environment. Chem Soc Rev. 2012 Apr 7;41(7):2780-99. doi:10.1039/C1CS15233E
41. Miao S, Zhu W, Castro NJ, Leng J, Zhang LG. Four-dimensional printing hierarchy scaffolds with highly biocompatible smart polymers for tissue engineering applications. Tissue Eng Part C Methods. 2016 Jul;22(6):584-93. doi:10.1089/ten.TEC.2015.0542
42. Walkey CD, Chan WC. Understanding nanomaterial-protein interactions. *Chem Soc Rev*. 2012;41(7):2780-99. doi:10.1039/C1CS15233E
43 . IRAN FDA. APPROVAL DOCUMENT OF SINADOXOSOME. REPORT NO.: IN-DF-2020-045; 2020.
44 . CHEN F, EHLERDING EB, CAI W. THERANOSTIC NANOPARTICLES. J NUCL MED. 2014 MAR;55(3):1919-22. DOI:10.2967/JNUMED.114.146019