Application of Functionalized Nanoparticles in Regulating Macrophage Polarization in Osteoarthritis

Ningyu Fan

doi:10.54097/har45x04

Authors

Ningyu Fan

DOI:

https://doi.org/10.54097/har45x04

Keywords:

Functionalized Nanoparticles, Macrophage Polarization, Osteoarthritis, Inflammation Regulation, Tissue Repair, Precision Medicine

Abstract

Osteoarthritis is a disease characterized primarily by chronic inflammation and joint degeneration, with a complex pathogenesis. Currently, there is no effective curative treatment. Macrophages play a key role in the inflammatory response and tissue repair in osteoarthritis, and the imbalance in their polarization is an important driving factor for the progression of the disease. Functionalized nanoparticles, with their high targeting ability and multifunctional properties, have shown great potential in regulating macrophage polarization, improving the inflammatory microenvironment, and promoting tissue repair. This paper reviews the role of functionalized nanoparticles in targeted delivery, signaling pathway regulation, and cytokine secretion, highlighting their mechanisms in modulating macrophage polarization. The paper systematically discusses the relationship between macrophage polarization and osteoarthritis, with a focus on preclinical experimental results. Functionalized nanoparticles have demonstrated significant therapeutic effects in alleviating inflammation, protecting cartilage, and promoting bone regeneration. Although there are still many challenges in terms of safety, targeting, and clinical translation, with the continuous development of nanotechnology, functionalized nanoparticles are expected to become an important breakthrough in the field of osteoarthritis treatment.

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References

[1] Qiu S, Shi Y, Zang H, et al. Multifunctional injectable microspheres for osteoarthritis therapy via spatiotemporally modulating macrophage polarization and inflammation[J]. NPJ Regenerative Medicine, 2024, 9(1): 3.DOI:10.1038/s41536-024-00368-w.

[2] Yuan Z, Jiang D, Yang M, Tao J, Hu X, Yang X, Zeng Y. Emerging Roles of Macrophage Polarization in Osteoarthritis: Mechanisms and Therapeutic Strategies. Orthop Surg. 2024 Mar;16(3):532-550. doi: 10.1111/os.13993. Epub 2024 Jan 31. PMID: 38296798; PMCID: PMC10925521.

[3] Yao Z, Qi W, Zhang H, Zhang Z, Liu L, Shao Y, Zeng H, Yin J, Pan H, Guo X, Liu A, Cai D, Bai X, Zhang H. Down-regulated GAS6 impairs synovial macrophage efferocytosis and promotes obesity-associated osteoarthritis. Elife. 2023 May 5;12: e83069. doi: 10.7554/eLife.83069. PMID: 37144868; PMCID: PMC10191622.

[4] Pang L, Jin H, Lu Z, Xie F, Shen H, Li X, Zhang X, Jiang X, Wu L, Zhang M, Zhang T, Zhai Y, Zhang Y, Guan H, Su J, Li M, Gao J. Treatment with Mesenchymal Stem Cell-Derived Nanovesicle-Containing Gelatin Methacryloyl Hydrogels Alleviates Osteoarthritis by Modulating Chondrogenesis and Macrophage Polarization. Adv Healthc Mater. 2023 Jul;12(17):e2300315. doi: 10.1002/adhm.202300315. Epub 2023 Mar 9. PMID: 36848378.

[5] Nedunchezhiyan U, Varughese I, Sun AR, Wu X, Crawford R, Prasadam I. Obesity, Inflammation, and Immune System in Osteoarthritis. Front Immunol. 2022 Jul 4;13:907750. doi: 10.3389/ fimmu. 2022. 907750. PMID: 35860250; PMCID: PMC9289681.

[6] Zou X, Xu H, Qian W. Macrophage Polarization in the Osteoarthritis Pathogenesis and Treatment. Orthop Surg. 2025 Jan;17(1):22-35. doi: 10.1111/os.14302. Epub 2024 Dec 5. PMID: 39638774; PMCID: PMC11735378.

[7] Fang C, Zhong R, Lu S, Yu G, Liu Z, Yan C, Gao J, Tang Y, Wang Y, Zhao Q, Feng X. TREM2 promotes macrophage polarization from M1 to M2 and suppresses osteoarthritis through the NF-κB/CXCL3 axis. Int J Biol Sci. 2024 Mar 11;20(6):1992-2007. doi: 10.7150/ijbs.91519. PMID: 38617547; PMCID: PMC11008261.

[8] Ko CY, Lin YY, Achudhan D, Chang JW, Liu SC, Lai CY, Huang YL, Tsai CH, Fong YC, Chen HT, Lee KT, Huang CC, Chang TK, Tang CH. Omentin-1 ameliorates the progress of osteoarthritis by promoting IL-4-dependent anti-inflammatory responses and M2 macrophage polarization. Int J Biol Sci. 2023 Oct 16;19(16):5275-5289. doi: 10.7150/ijbs.86701. PMID: 37928270; PMCID: PMC10620827.

[9] Liu B, Xian Y, Chen X, Shi Y, Dong J, Yang L, An X, Shen T, Wu W, Ma Y, He Y, Gong W, Peng R, Lin J, Liu N, Guo B, Jiang Q. Inflammatory Fibroblast-Like Synoviocyte-Derived Exosomes Aggravate Osteoarthritis via Enhancing Macrophage Glycolysis. Adv Sci (Weinh). 2024 Apr;11(14): e2307338. doi: 10.1002/advs.202307338. Epub 2024 Feb 11. PMID: 38342630; PMCID: PMC11005727.

[10] Wu CL, Harasymowicz NS, Klimak MA, Collins KH, Guilak F. The role of macrophages in osteoarthritis and cartilage repair. Osteoarthritis Cartilage. 2020 May;28(5):544-554. doi: 10.1016/j.joca.2019.12.007. Epub 2020 Jan 8. PMID: 31926267; PMCID: PMC7214213.

[11] Wang L, He C. Nrf2-mediated anti-inflammatory polarization of macrophages as therapeutic targets for osteoarthritis. Front Immunol. 2022 Aug 12; 13:967193. doi: 10.3389/fimmu.2022.967193. PMID: 360 32081; PMCID: PMC9411667.

[12] Sun H, Sun Z, Xu X, Lv Z, Li J, Wu R, Fei Y, Tan G, Liu Z, Liu Y, Shi D. Blocking TRPV4 Ameliorates Osteoarthritis by Inhibiting M1 Macrophage Polarization via the ROS/NLRP3 Signaling Pathway. Antioxidants (Basel). 2022 Nov 23;11(12):2315. doi: 10.3390/antiox11122315. PMID: 36552524; PMCID: PMC9774183.

[13] He XX, Huang YJ, Hu CL, Xu QQ, Wei QJ. Songorine modulates macrophage polarization and metabolic reprogramming to alleviate inflammation in osteoarthritis. Front Immunol. 2024 Feb 13; 15:1344949. doi: 10.3389/fimmu.2024.1344949. PMID: 38415250; PMCID: PMC10896988.

[14] Liu X, Ren X, Zhou L, Liu K, Deng L, Qing Q, Li J, Zhi F, Li M. Tollip Orchestrates Macrophage Polarization to Alleviate Intestinal Mucosal Inflammation. J Crohns Colitis. 2022 Aug 4;16(7):1151-1167. doi: 10.1093/ecco-jcc/jjac019. PMID: 35134154.

[15] Yang J, Li S, Li Z, Yao L, Liu M, Tong KL, Xu Q, Yu B, Peng R, Gui T, Tang W, Xu Y, Chen J, He J, Zhao K, Wang X, Wang X, Zha Z, Zhang HT. Targeting YAP1-regulated Glycolysis in Fibroblast-Like Synoviocytes Impairs Macrophage Infiltration to Ameliorate Diabetic Osteoarthritis Progression. Adv Sci (Weinh). 2024 Feb;11(5): e2304617. doi: 10.1002/advs.202304617. Epub 2023 Dec 3. PMID: 38044289; PMCID: PMC10837355.

[16] Wu B, Pan W, Luo S, Luo X, Zhao Y, Xiu Q, Zhong M, Wang Z, Liao T, Li N, Liu C, Nie C, Yi G, Lin S, Zou M, Li B, Zheng L. Turmeric-Derived Nanoparticles Functionalized Aerogel Regulates Multicellular Networks to Promote Diabetic Wound Healing. Adv Sci (Weinh). 2024 May;11 (18): e230 7630. doi: 10.1002/advs.202307630. Epub 2024 Mar 5. PMID: 38441389; PMCID: PMC11095230.

[17] Lu Q, Kou D, Lou S, Ashrafizadeh M, Aref AR, Canadas I, Tian Y, Niu X, Wang Y, Torabian P, Wang L, Sethi G, Tergaonkar V, Tay F, Yuan Z, Han P. Nanoparticles in tumor microenvironment remodeling and cancer immunotherapy. J Hematol Oncol. 2024 Apr 2;17(1):16. doi: 10.1186/s13045-024-01535-8. PMID: 38566199; PMCID: PMC10986145.

[18] Zhou J, Liu W, Zhao X, Xian Y, Wu W, Zhang X, Zhao N, Xu FJ, Wang C. Natural Melanin/Alginate Hydrogels Achieve Cardiac Repair through ROS Scavenging and Macrophage Polarization. Adv Sci (Weinh). 2021 Oct;8(20): e2100505. doi: 10.1002/advs.202100505. Epub 2021 Aug 19. PMID: 34414693; PMCID: PMC8529445.

[19] Li JM, Li X, Chan LWC, Hu R, Zheng T, Li H, Yang S. Lipotoxicity-polarised macrophage-derived exosomes regulate mitochondrial fitness through Miro1-mediated mitophagy inhibition and contribute to type 2 diabetes development in mice. Diabetologia. 2023 Dec;66(12):2368-2386. doi: 10.1007/s00125-023-05992-7. Epub 2023 Aug 24. PMID: 37615690.

[20] Bian F, Lan YW, Zhao S, Deng Z, Shukla S, Acharya A, Donovan J, Le T, Milewski D, Bacchetta M, Hozain AE, Tipograf Y, Chen YW, Xu Y, Shi D, Kalinichenko VV, Kalin TV. Lung endothelial cells regulate pulmonary fibrosis through FOXF1/R-Ras signaling. Nat Commun. 2023 May 4;14(1):2560. doi: 10.1038/s41467-023-38177-2. PMID: 37137915; PMCID: PMC10156846.

[21] Ding H, Zhang Y, Mao Y, Li Y, Shen Y, Sheng J, Gu N. Modulation of macrophage polarization by iron-based nanoparticles. Med Rev (2021). 2023 Apr 18;3(2):105-122. doi: 10.1515/mr-2023-0002. PMID: 37724082; PMCID: PMC10471121.

[22] Liu X, Fei H, Yang C, Wang J, Zhu X, Yang A, Shi Z, Jin X, Yang F, Wu D, Jiang L, Zhang S. Trophoblast-Derived Extracellular Vesicles Promote Preeclampsia by Regulating Macrophage Polarization. Hypertension. 2022 Oct;79(10):2274-2287. doi: 10.1161/ HYPERTENSIONAHA. 122. 19244. Epub 2022 Aug 22. PMID: 35993233.

[23] Liu X, Guo C, Yang W, Wang W, Diao N, Cao M, Cao Y, Wang X, Wang X, Pei H, Jiang Y, Kong M, Chen D. Composite microneedles loaded with Astragalus membranaceus polysaccharide nanoparticles promote wound healing by curbing the ROS/NF-κB pathway to regulate macrophage polarization. Carbohydr Polym. 2024 Dec 1; 345:122574. doi: 10.1016/j.carbpol.2024.122574. Epub 2024 Aug 6. PMID: 39227108.

[24] Zhao G, Xue L, Geisler HC, Xu J, Li X, Mitchell MJ, Vaughan AE. Precision treatment of viral pneumonia through macrophage-targeted lipid nanoparticle delivery. Proc Natl Acad Sci U S A. 2024 Feb 13; 121 (7): e2314747121. doi: 10.1073/pnas.2314747121. Epub 2024 Feb 5. PMID: 38315853; PMCID: PMC 10873611.

[25] Li H, Yuan Y, Zhang L, Xu C, Xu H, Chen Z. Reprogramming Macrophage Polarization, Depleting ROS by Astaxanthin and Thioketal-Containing Polymers Delivering Rapamycin for Osteoarthritis Treatment. Adv Sci (Weinh). 2024 Mar;11(9):e2305363. doi: 10.1002/advs.202305363. Epub 2023 Dec 14. PMID: 38093659; PMCID: PMC10916582.

[26] Xu L, Xing Z, Yuan J, Han Y, Jiang Z, Han M, Hou X, Xing W, Li Z. Ultrasmall Nanoparticles Regulate Immune Microenvironment by Activating IL-33/ST2 to Alleviate Renal Ischemia-Reperfusion Injury. Adv Healthc Mater. 2024 May;13(13):e2303276. doi: 10.1002/adhm.202303276. Epub 2024 Feb 21. PMID: 38335143.

[27] Zhang P, Miska J, Heimberger AB. GLUT3 regulates alternative macrophage signaling through a glucose transport-independent role. J Clin Invest. 2023 Nov 1;133(21):e174540. doi: 10.1172/JCI174540. PMID: 37909335; PMCID: PMC10617759.

[28] Deng, Q. S., Gao, Y., Rui, B. Y., Li, X. R., Liu, P. L., Han, Z. Y., Wei, Z. Y., Zhang, C. R., Wang, F., Dawes, H., Zhu, T. H., Tao, S. C., & Guo, S. C. (2023). Double-network hydrogel enhanced by SS31-loaded mesoporous polydopamine nanoparticles: Symphonic collaboration of near-infrared photothermal antibacterial effect and mitochondrial maintenance for full-thickness wound healing in diabetes mellitus. Bioactive materials, 27, 409–428. https://doi.org/10.1016/j.bioactmat.2023.04.004

[29] Ni C, Zhou J, Kong N, Bian T, Zhang Y, Huang X, Xiao Y, Yang W, Yan F. Gold nanoparticles modulate the crosstalk between macrophages and periodontal ligament cells for periodontitis treatment. Biomaterials. 2019 Jun;206:115-132. doi: 10.1016/j.biomaterials.2019.03.039. Epub 2019 Mar 25. PMID: 30933774.

[30] Han, X., Luo, R., Qi, S., Wang, Y., Dai, L., Nie, W., Lin, M., He, H., Ye, N., Fu, C., You, Y., Fu, S., & Gao, F. (2023). "Dual sensitive supramolecular curcumin nanoparticles" in "advanced yeast particles" mediate macrophage reprogramming, ROS scavenging and inflammation resolution for ulcerative colitis treatment. Journal of nanobiotechnology, 21(1), 321. https://doi.org/10.1186/s12951-023-01976-2

[31] He TR, Tang XY, Yan Q, Wu XY, Shi B, Lin Y. All-trans Retinoic Acid-incorporated Glycol Chitosan Nanoparticles Regulate Macrophage Polarization in Pg-LPS-Induced Inflammation. Curr Med Sci. 2022 Oct;42(5):974-980. doi: 10.1007/s11596-022-2602-8. Epub 2022 Oct 17. PMID: 36245026.

[32] Liu X, Ou X, Zhang T, Li X, Qiao Q, Jia L, Xu Z, Zhang F, Tian T, Lan H, Yang C, Kong L, Zhang Z. In situ neutrophil apoptosis and macrophage efferocytosis mediated by Glycyrrhiza protein nanoparticles for acute inflammation therapy. J Control Release. 2024 May; 369:215-230. doi: 10.1016/j. jconrel. 2024.03.029. Epub 2024 Mar 28. PMID: 38508529.

[33] Zhang M, Hu W, Cai C, Wu Y, Li J, Dong S. Advanced application of stimuli-responsive drug delivery system for inflammatory arthritis treatment. Mater Today Bio. 2022 Feb 21;14:100223. doi: 10.1016/ j. mtbio. 2022.100223. PMID: 35243298; PMCID: PMC8881671.

[34] Luo J, Zhang Y, Zhu S, Tong Y, Ji L, Zhang W, Zhang Q, Bi Q. The application prospect of metal/metal oxide nanoparticles in the treatment of osteoarthritis. Naunyn Schmiedebergs Arch Pharmacol. 2021 Oct;394(10):1991-2002. doi: 10.1007/s00210-021-02131-0. Epub 2021 Aug 20. PMID: 34415355; PMCID: PMC8486704.

[35] Ma JC, Luo T, Feng B, Huang Z, Zhang Y, Huang H, Yang X, Wen J, Bai X, Cui ZK. Exploring the translational potential of PLGA nanoparticles for intra-articular rapamycin delivery in osteoarthritis therapy. J Nanobiotechnology. 2023 Oct 4;21(1):361. doi: 10.1186/s12951-023-02118-4. PMID: 3779 4470; PMCID: PMC10548624.

[36] Liang H, Yan Y, Sun W, Ma X, Su Z, Liu Z, Chen Y, Yu B. Preparation of Melatonin-Loaded Nanoparticles with Targeting and Sustained Release Function and Their Application in Osteoarthritis. Int J Mol Sci. 2023 May 14;24(10):8740. doi: 10.3390/ijms24108740. PMID: 37240086; PMCID: PMC 10217911.

[37] Liu S, Zhang C, Zhou Y, Zhang F, Duan X, Liu Y, Zhao X, Liu J, Shuai X, Wang J, Cao Z. MRI-visible mesoporous polydopamine nanoparticles with enhanced antioxidant capacity for osteoarthritis therapy. Biomaterials. 2023 Apr; 295: 122030. doi: 10.1016/j.biomaterials.2023.122030. Epub 2023 Jan 31. PMID: 36758340.

[38] Zheng L, Zhao S, Li Y, Xu J, Yan W, Guo B, Xu J, Jiang L, Zhang Y, Wei H, Jiang Q. Engineered MgO nanoparticles for cartilage-bone synergistic therapy. Sci Adv. 2024 Mar 8;10(10):eadk6084. doi: 10.1126/sciadv. adk6084. Epub 2024 Mar 8. Erratum in: Sci Adv. 2024 Jul 19;10(29):eadr4798. doi: 10.1126/sciadv. adr4798. PMID: 38457498; PMCID: PMC10923500.

[39] Ma X, Luan Z, Li J. Inorganic Nanoparticles-Based Systems in Biomedical Applications of Stem Cells: Opportunities and Challenges. Int J Nanomedicine. 2023 Jan 7; 18:143-182. doi: 10.2147/IJN.S384343. PMID: 36643862; PMCID: PMC9833678.

[40] Liu X, Corciulo C, Arabagian S, Ulman A, Cronstein BN. Adenosine-Functionalized Biodegradable PLA-b-PEG Nanoparticles Ameliorate Osteoarthritis in Rats. Sci Rep. 2019 May 15;9(1):7430. doi: 10.1038/s41598-019-43834-y. PMID: 31092864; PMCID: PMC6520388.

[41] Chen H, Chen F, Hu F, Li Y, Zhang M, Zhou Q, Ding T, Tulufu N, Ye T, Wang F, Guo L. MicroRNA-224-5p nanoparticles balance homeostasis via inhibiting cartilage degeneration and synovial inflammation for synergistic alleviation of osteoarthritis. Acta Biomater. 2023 Sep 1;167:401-415. doi: 10.1016/j.actbio.2023.06.010. Epub 2023 Jun 15. PMID: 37330028.

[42] Wu H, Wang J, Lin Y, He W, Hou J, Deng M, Chen Y, Liu Q, Lu A, Cui Z, Guan D, Yu B. Injectable Ozone-Rich Nanocomposite Hydrogel Loaded with D-Mannose for Anti-Inflammatory and Cartilage Protection in Osteoarthritis Treatment. Small. 2024 Jun;20(25):e2309597. doi: 10.1002/smll.202309597. Epub 2024 Jan 26. PMID: 38279613.

[43] Park H, Lee HR, Shin HJ, Park JA, Joo Y, Kim SM, Beom J, Kang SW, Kim DW, Kim J. p16INK4a-siRNA nanoparticles attenuate cartilage degeneration in osteoarthritis by inhibiting inflammation in fibroblast-like synoviocytes. Biomater Sci. 2022 Jun 14;10(12):3223-3235. doi: 10.1039/d1bm01941d. PMID: 35579255.

[44] Rong M, Liu D, Xu X, Li A, Bai Y, Yang G, Liu K, Zhang Z, Wang L, Wang K, Lu L, Jiang Y, Liu J, Zhang X. A Superparamagnetic Composite Hydrogel Scaffold as In Vivo Dynamic Monitorable Theranostic Platform for Osteoarthritis Regeneration. Adv Mater. 2024 Aug;36(35):e2405641. doi: 10.1002/adma.202405641. Epub 2024 Jul 6. PMID: 38877353.

[45] Brady MA, Waldman SD, Ethier CR. The application of multiple biophysical cues to engineer functional neocartilage for treatment of osteoarthritis. Part II: signal transduction. Tissue Eng Part B Rev. 2015 Feb;21(1):20-33. doi: 10.1089/ten.TEB.2013.0760. Epub 2014 Oct 24. PMID: 25065615.

[46] Wu C, Huang Z, Chen J, Li N, Cai Y, Chen J, Ruan G, Han W, Ding C, Lu Y. Efficiently directing differentiation and homing of mesenchymal stem cells to boost cartilage repair in osteoarthritis via a nanoparticle and peptide dual-engineering strategy. Biomaterials. 2025 Jan; 312:122720. doi: 10.1016/j. biomaterials.2024.122720. Epub 2024 Jul 27. PMID: 39084098.

[47] Dos Santos Haupenthal DP, Resmini MB, Da Silva LA, Colares MC, de Roch Casagrande L, Milanez Venturini L, de Andrade TAM, do Bomfim FRC, Thirupathi A, Emilio Feuser P, Dal Pizzol F, Silveira PCL. Intra-articular Treatment with Triamcinolone Hexacetonide Associated with Gold Nanoparticles Reduces Cartilage Degeneration in an Animal Model of Osteoarthritis. Curr Drug Targets. 2023;24(3):287-296. doi: 10.2174/1389450124666221212090319. PMID: 36515017.

[48] Huang H, Yang L, He H, Zhou B, Qin Z, Zheng L, Shen C. Construction of mitochondrial-targeting nano-prodrug for enhanced Rhein delivery and treatment for osteoarthritis in vitro. Int J Pharm. 2024 Aug 15;661: 124397. doi: 10.1016/j.ijpharm.2024.124397. Epub 2024 Jun 28. PMID: 38945463.

[49] Li T, Guo M, Zhang W. Comparison of Therapeutic Effects of Topical Application of Diclofenac Sodium Nanoparticles and Conventional Placebo on Knee Osteoarthritis. Cell Mol Biol (Noisy-le-grand). 2022 Mar 31;68(3):171-178. doi: 10.14715/cmb/2022.68.3.20. PMID: 35988175.

[50] Zerrillo L, Gigliobianco MR, D'Atri D, Garcia JP, Baldazzi F, Ridwan Y, Fuentes G, Chan A, Creemers LB, Censi R, Di Martino P, Cruz LJ. PLGA Nanoparticles Grafted with Hyaluronic Acid to Improve Site-Specificity and Drug Dose Delivery in Osteoarthritis Nanotherapy. Nanomaterials (Basel). 2022 Jun 30;12(13):2248. doi: 10.3390/nano12132248. PMID: 35808084; PMCID: PMC9268068.

[51] Mayorga C, Perez-Inestrosa E, Rojo J, Ferrer M, Montañez MI. Role of nanostructures in allergy: Diagnostics, treatments and safety. Allergy. 2021 Nov;76(11):3292-3306. doi: 10.1111/all.14764. Epub 2021 Mar 9. PMID: 33559903.

[52] Liu F, Mao K, Chen H, Cong X, Tan H, Xin Y, Wang X, Ke J, Song Y, Yang YG, Sun T. Enhancing the Safety and Efficacy of Trastuzumab Emtansine (T-DM1) Through Nano-Delivery System in Breast Cancer Therapy. Small. 2024 Dec;20(50):e2400977. doi: 10.1002/smll.202400977. Epub 2024 Oct 6. PMID: 39370652.

[53] Ho TL, Mutalik C, Rethi L, Nguyen HT, Jheng PR, Wong CC, Yang TS, Nguyen TT, Mansel BW, Wang CA, Chuang EY. Cancer-targeted fucoidan‑iron oxide nanoparticles for synergistic chemotherapy/ chemodynamic theranostics through amplification of P-selectin and oxidative stress. Int J Biol Macromol. 2023 Apr 30; 235: 123821. doi: 10.1016/j.ijbiomac.2023.123821. Epub 2023 Mar 2. PMID: 36870633.

[54] Zhang J, Liu S, Wang Y, Li X, Zeng H, Li B, Wang J. Preparation of Chitosan Nanoparticles through a Readily Solvent-Exchange Process for Efficient and Enhanced Gene Delivery. Langmuir. 2024 May 21;40(20):10486-10491. doi: 10.1021/acs.langmuir.3c03874. Epub 2024 May 10. PMID: 38728233.

[55] Di Felice G, Colombo P. Nanoparticle-allergen complexes for allergen immunotherapy. Int J Nanomedicine. 2017 Jun 19;12: 4493-4504. doi: 10.2147/IJN.S134630. PMID: 28684909; PMCID: PMC 5484593.

[56] Shmueli RB, Bhise NS, Green JJ. Evaluation of polymeric gene delivery nanoparticles by nanoparticle tracking analysis and high-throughput flow cytometry. J Vis Exp. 2013 Mar 1;(73): e50176. doi: 10.3791/50176. PMID: 23486314; PMCID: PMC3622088.

[57] Eloy JO, Petrilli R, Trevizan LNF, Chorilli M. Immunoliposomes: A review on functionalization strategies and targets for drug delivery. Colloids Surf B Biointerfaces. 2017 Nov 1; 159:454-467. doi: 10.1016/j. colsurfb. 2017. 07.085. Epub 2017 Aug 5. PMID: 28837895.