Exosome-functionalized carbonate apatite nanoparticles as potential immunomodulatory mucosal vaccine adjuvant: physicochemical characterization and cytocompatibility on macrophages and buccal epithelial cells
Source abstract
Abstract
Mucosal vaccines offer a promising strategy for inducing site-specific immunity, but their effectiveness depends heavily on safe and efficient delivery systems. This study aims to study exosome-functionalized carbonate apatite (CHA-EXO) nanoparticles as a novel immunomodulatory adjuvant for oral mucosal vaccination. The CHA nanoparticles were synthesized and functionalized with mesenchymal stem cell-derived exosomes with physical adsorption. Their physicochemical properties, including functional groups, morphology, size distribution, and surface charge, were characterized. Loading efficiency and stability were observed with Bradford assays. Cytocompatibility was assessed in RAW264.7 and TR146 cells using the MTT assay. Comparative analysis was performed against aluminum hydroxide as a conventional adjuvant. The synthesized CHA-EXO nanoparticles exhibited a nanoscale diameter of approximately 100–120 nm, with a moderate increase in size following exosome functionalization in a concentration-dependent manner. They maintained a stable dispersion, showing surface charges of −31.63 to −37.48 mV in water and around −26 mV in artificial saliva. The nanoparticles demonstrated high cytocompatibility in both TR146 and RAW264.7 cells (> 75% viability), performing better than aluminum hydroxide at comparable moderate doses. Furthermore, the functionalized nanoparticles formed stable complexes with high loading efficiency, reaching 93.89% at elevated exosome concentrations, and released only 19.40% of the cargo within 24 h. These findings indicate exosome immobilization and enhanced potential for increased cellular interaction. The CHA-EXO nanoparticles show promise as a stable and biocompatible oral mucosal adjuvant, offering both physicochemical stability and favorable cell interactions.
Source: openaire · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Advanced Drug Delivery Systems · Extracellular vesicles in disease · RNA Interference and Gene Delivery
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (49)
Show source-provided references
1. Vaernewyck V, Arzi B, Sanders NN, Cox E, Devriendt B (2021) Mucosal vaccination against periodontal disease: current status and opportunities. Front Immunol 2:12
2. Ou B, Yang Y, Lv H, Lin X, Zhang M (2023) Current progress and challenges in the study of adjuvants for oral vaccines. BioDrugs 37(2):143–18010.1007/s40259-022-00575-1 ↗
3. Vela Ramirez JE, Sharpe LA, Peppas NA (2017) Current state and challenges in developing oral vaccines. Adv Drug Deliv Rev 15(114):116–13110.1016/j.addr.2017.04.008 ↗
4. Freytag LC, Clements JD (2015) Mucosal adjuvants: new developments and challenges. In: Mestecky J, Strober W, Russell MW, Kelsall BL, Cheroutre H, Lambrecht BN (eds) Mucosal immunology: 4th Edition. Elsevier Inc. pp 1183–99
5. Rhee JH, Lee SE, Kim SY (2012) Mucosal vaccine adjuvants update. Clin Exp Vaccine Res 1(1):5010.7774/cevr.2012.1.1.50 ↗
6. Sarasati A, Wihadmadyatami H, Ana ID (2023) Carbonate apatite nanoparticles: a novel nano-adjuvant for oral mucosal vaccines and immunomodulator. OpenNano 12(100149):1–13
7. Yotsova R, Peev S (2024) Biological properties and medical applications of carbonate apatite: a systematic review. Pharmaceutics 16(2):29110.3390/pharmaceutics16020291 ↗
8. Anggraeni R, Ana ID, Wihadmadyatami H (2022) Development of mucosal vaccine delivery: an overview on the mucosal vaccines and their adjuvants. Clin Exp Vaccine Res 11(3):235–24810.7774/cevr.2022.11.3.235 ↗
9. Anggraeni R, Martien R, Agustina D, Ana ID (2018) Incorporation of ovalbumin into carbonate apatite as a candidate for protein delivery. Key Eng Mater 782:27–3110.4028/www.scientific.net/KEM.782.27 ↗
10. Sarasati A, Syahruddin MH, Nuryanti A, Ana ID, Barlian A, Wijaya CH et al (2023) Plant-derived exosome-like nanoparticles for biomedical applications and regenerative therapy. Biomedicines 11(4):105310.3390/biomedicines11041053 ↗
11. Ana ID, Barlian A, Hidajah AC, Wijaya CH, Notobroto HB, Kencana Wungu TD (2021) Challenges and strategy in treatment with exosomes for cell-free-based tissue engineering in dentistry. Future Sci OA 7(10):1–2110.2144/fsoa-2021-0050 ↗
12. Liu X, Teng X, Wang J, Zhang G, Guo W, Zhang W et al (2025) Exosome-based mucosal therapeutic and diagnostic system: towards clinical translation. J Control Release 10:385
13. Liu H, Zhang M, Shi M, Zhang T, Lu W, Yang S et al (2021) Adipose-derived mesenchymal stromal cell-derived exosomes promote tendon healing by activating both SMAD1/5/9 and SMAD2/3. Stem Cell Res Ther 12(1):33810.1186/s13287-021-02410-w ↗
14. Langen EN, Rumampuk JF, Leman MA (2017) Pengaruh saliva buatan dan belimbing wuluh (Averrhoa bilimbi L.) terhadap kekerasan resin komposit nano hybrid. PHARMACON Jurnal Ilmiah Farmasi-UNSRAT 6(1):9–15
15. Hendarmin LA, Novianita B, Anggraeni Y, Febriyanti K (2024) Exploring the potential of tomato juice (Solanum lycopersicum L.) patch for tooth bleaching. J Dent Res Dent Clin Dent Prospects 18:157–16410.34172/joddd.41042 ↗
16. Jung MK, Mun JY (2018) Sample preparation and imaging of exosomes by transmission electron microscopy. J Vis Exp 2018(131):5648210.3791/56482 ↗
17. Toda T, Yoshino S (2016) Enhancement of ovalbumin-specific Th1, Th2, and Th17 immune responses by amorphous silica nanoparticles. Int J Immunopathol Pharmacol 29(3):408–42010.1177/0394632016656192 ↗
18. Yaghoobi N, Majidi RF, Faramarzi MA, Baharifar H, Amani A (2017) Preparation, optimization and activity evaluation of PLGA/streptokinase nanoparticles using electrospray. Adv Pharm Bull 7(1):131–13910.15171/apb.2017.017 ↗
19. Nikapitiya C, Jayathilaka EHTT, Edirisinghe SL, Rajapaksha DC, Wasana WP, Jayasinghe JNC et al (2022) Isolation and characterization of plasma-derived exosomes from the marine fish rock bream (Oplegnathus fasciatus) by two isolation techniques. Fishes 7(1):3610.3390/fishes7010036 ↗
20. Zhang Y, Huang T, Jorgens DM, Nickerson A, Lin LJ, Pelz J et al (2017) Quantitating morphological changes in biological samples during scanning electron microscopy sample preparation with correlative super-resolution microscopy. PLoS One 12(5):e017683910.1371/journal.pone.0176839 ↗
21. Cacioppo M, De Zorzi R, Syrgiannis Z, Bellich B, Bertoncin P, Jou IA et al (2023) Microscopy and modelling investigations on the morphology of the biofilm exopolysaccharide produced by Burkholderia multivorans strain C1576. Int J Biol Macromol 31:253
22. Wang J, Zhao Z, Wang Q, Shi J, Wong DWC, Cheung JCW (2024) Advancements in nanoparticle-based adjuvants for enhanced tuberculosis vaccination: a review. Vaccines (Basel) 12(12):133510.3390/vaccines12121335 ↗
23. Zheng Y, Luo S, Xu M, He Q, Xie J, Wu J et al (2024) Transepithelial transport of nanoparticles in oral drug delivery: from the perspective of surface and holistic property modulation. Acta Pharm Sin B Chin Acad Med Sci 14:3876–390010.1016/j.apsb.2024.06.015 ↗
24. Banerjee A, Qi J, Gogoi R, Wong J, Mitragotri S (2016) Role of nanoparticle size, shape and surface chemistry in oral drug delivery. J Control Release 28(238):176–18510.1016/j.jconrel.2016.07.051 ↗
25. Beit-Yannai E, Tabak S, Stamer WD (2018) Physical exosome:exosome interactions. J Cell Mol Med 22(3):2001–200610.1111/jcmm.13479 ↗
26. Danaei M, Dehghankhold M, Ataei S, Hasanzadeh Davarani F, Javanmard R, Dokhani A et al (2018) Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics 10(2):5710.3390/pharmaceutics10020057 ↗
27. Németh Z, Csóka I, Semnani Jazani R, Sipos B, Haspel H, Kozma G et al (2022) Quality by design-driven zeta potential optimisation study of liposomes with charge imparting membrane additives. Pharmaceutics 14(9):179810.3390/pharmaceutics14091798 ↗
28. Pokrowiecki R, Wojnarowicz J, Zareba T, Koltsov I, Lojkowski W, Tyski S et al (2019) Nanoparticles and human saliva: a step towards drug delivery systems for dental and craniofacial biomaterials. Int J Nanomedicine 14:9235–925710.2147/IJN.S221608 ↗
29. Teubl BJ, Stojkovic B, Docter D, Pritz E, Leitinger G, Poberaj I et al (2018) The effect of saliva on the fate of nanoparticles. Clin Oral Investig 22(2):929–94010.1007/s00784-017-2172-5 ↗
30. Schubert J, Chanana M (2018Jun 4) Coating matters: review on colloidal stability of nanoparticles with biocompatible coatings in biological media, living cells and organisms. Curr Med Chem 25(35):4553–458610.2174/0929867325666180601101859 ↗
31. Wong LW, Mak SH, Goh BH, Lee WL (2023) The convergence of FTIR and EVs: emergence strategy for non-invasive cancer markers discovery. Diagnostics 13(1)10.3390/diagnostics13010022 ↗
32. Wang K, Wang MH, Wang QG, Lu X, Zhang XD (2017) Computer simulation of proteins adsorption on hydroxyapatite surfaces with calcium phosphate ions. J Eur Ceram Soc 37(6):2509–252010.1016/j.jeurceramsoc.2017.02.013 ↗
33. Mihály J, Deák R, Szigyártó IC, Bóta A, Beke-Somfai T, Varga Z (2017) Characterization of extracellular vesicles by IR spectroscopy: fast and simple classification based on amide and C[sbnd]H stretching vibrations. Biochim Biophys Acta Biomembr 1859(3):459–46610.1016/j.bbamem.2016.12.005 ↗
34. Parikh SJ, Mukome FND, Zhang X (2014) ATR-FTIR spectroscopic evidence for biomolecular phosphorus and carboxyl groups facilitating bacterial adhesion to iron oxides. Colloids Surf B Biointerfaces 1(119):38–4610.1016/j.colsurfb.2014.04.022 ↗
35. Lee WH, Loo CY, Rohanizadeh R (2014) s: effects on protein adsorption and cellular response. Colloids Surf B Biointerfaces 1(122):823–83410.1016/j.colsurfb.2014.07.029 ↗
36. Swain SK, Sarkar D (2013) Study of BSA protein adsorption/release on hydroxyapatite nanoparticles. Appl Surf Sci 1(286):99–10310.1016/j.apsusc.2013.09.027 ↗
37. Chakraborty D, Ethiraj KR, Mukherjee A (2020) Understanding the relevance of protein corona in nanoparticle-based therapeutics and diagnostics. RSC Adv 10(45):27161–2717210.1039/D0RA05241H ↗
38. Ho YT, Azman NA, Loh FWY, Ong GKT, Engudar G, Kriz SA et al (2018) Protein corona formed from different blood plasma proteins affects the colloidal stability of nanoparticles differently. Bioconjug Chem 29(11):3923–393410.1021/acs.bioconjchem.8b00743 ↗
39. Nicolle L, Journot CMA, Gerber-Lemaire S (2021) Chitosan functionalization: covalent and non-covalent interactions and their characterization. Polymers (Basel) 13(23):411810.3390/polym13234118 ↗
40. Wang Z, Shimabukuro M, Kishida R, Yokoi T, Kawashita M (2024) Effects of pH on the microarchitecture of carbonate apatite granules fabricated through a dissolution–precipitation reaction. Front Bioeng Biotechnol. https://doi.org/10.3389/fbioe.2024.139627510.3389/fbioe.2024.1396275 ↗
41. Ding Y, Luo Q, Que H, Wang N, Gong P, Gu J (2022) Mesenchymal stem cell-derived exosomes: a promising therapeutic agent for the treatment of liver diseases. Int J Mol Sci 23(18):1097210.3390/ijms231810972 ↗
42. Djouina M, Esquerre N, Desreumaux P, Vignal C, Body-Malapel M (2016) Toxicological consequences of experimental exposure to aluminum in human intestinal epithelial cells. Food Chem Toxicol 1(91):108–11610.1016/j.fct.2016.03.008 ↗
43. Zhu S, Huang H, Liu D, Wen S, Shen L, Lin Q (2022) Augmented cellular uptake and homologous targeting of exosome-based drug loaded IOL for posterior capsular opacification prevention and biosafety improvement. Bioact Mater 1(15):469–481
44. Liam-Or R, Faruqu FN, Walters A, Han S, Xu L, Wang JTW et al (2024) Cellular uptake and in vivo distribution of mesenchymal-stem-cell-derived extracellular vesicles are protein corona dependent. Nat Nanotechnol 19(6):846–85510.1038/s41565-023-01585-y ↗
45. Shen YQ, Sun L, Wang SM, Zheng XY, Xu R (2024) Exosomal integrins in tumor progression, treatment and clinical prediction (review). Int J Oncol. https://doi.org/10.3892/ijo.2024.570610.3892/ijo.2024.5706 ↗
46. Adjei IM, Sharma B, Labhasetwar V (2014) Nanoparticles: cellular uptake and cytotoxicity. Adv Exp Med Biol 811:74–91
47. Yong T, Zhang X, Bie N, Zhang H, Zhang X, Li F et al (2019) Tumor exosome-based nanoparticles are efficient drug carriers for chemotherapy. Nat Commun 10(1):383810.1038/s41467-019-11718-4 ↗
48. Fathi P, Rao L, Chen X (2021) Extracellular vesicle-coated nanoparticles. View 2(2):1–9
49. Soni S, O’Dea KP, Abe E, Khamdan M, Shah SV, Sarathchandra P et al (2022) Microvesicle-mediated communication within the alveolar space: mechanisms of uptake by epithelial cells and alveolar macrophages. Front Immunol 13:85376910.3389/fimmu.2022.853769 ↗