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State of the Art of Silica Nanoparticles: An Overview on Biodistribution and Preclinical Toxicity Studies

  • Review Article-theme
  • Recent Advances in Drug Delivery
  • Published:
The AAPS Journal Aims and scope Submit manuscript

Abstract

Over the past few years, nanoparticles have drawn particular attention in designing and developing drug delivery systems due to their distinctive advantages like improved pharmacokinetics, reduced toxicity, and specificity. Along with other successful nanosystems, silica nanoparticles (SNPs) have shown promising effects for therapeutic and diagnostic purposes. These nanoparticles are of great significance owing to their modifiable surface with various ligands, tunable particle size, and large surface area. The rate and extent of degradation and clearance of SNPs depend on factors such as size, shape, porosity, and surface modification, which directly lead to varying toxic mechanisms. Despite SNPs’ enormous potential for clinical and pharmaceutical applications, safety concerns have hindered their translation into the clinic. This review discusses the biodistribution, toxicity, and clearance of SNPs and the formulation-related factors that ultimately influence clinical efficacy and safety for treatment. A holistic view of SNP safety will be beneficial for developing an enabling SNP-based drug product.

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Data Availability

This is a review article without original data collected. All the cited data were documented with the original source.

Abbreviations

EPR:

Enhanced permeability and retention

FITC:

Fluorescein isothiocyanate

HUVEC:

Human umbilical vein endothelial cells

ID:

Injected dose

IL:

Interleukin

LDH:

Lactate dehydrogenase

MAPK:

Mitogen-activated protein kinase

MSN:

Mesoporous silica nanoparticles

MTD:

Maximum tolerated dose

NF-κB:

Nuclear factor kappa B

NOX2:

NADPH oxidase 2

PEG:

Polyethylene glycol

RES:

Reticuloendothelial systems

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

SNP:

Silica nanoparticle

TEM:

Transmission electron microscopy

TNF:

Tumor necrosis factor

TXNIP:

Thioredoxin-interacting protein

References

  1. Ren X, Cheng S, Liang Y, Yu X, Sheng J, Wan Y, et al. Mesoporous silica nanospheres as nanocarriers for poorly soluble drug itraconazole with high loading capacity and enhanced bioavailability. Microporous Mesoporous Mater. 2020;305:110389.

    Article  CAS  Google Scholar 

  2. Yusuf A, Almotairy ARZ, Henidi H, Alshehri OY, Aldughaim MS. Nanoparticles as drug delivery systems: a review of the implication of nanoparticles’ physicochemical properties on responses in biological systems. Polymers. 2023;15(7):1596.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Yuan H, Guo H, Luan X, He M, Li F, Burnett J, et al. Albumin nanoparticle of paclitaxel (abraxane) decreases while taxol increases breast cancer stem cells in treatment of triple negative breast cancer. Mol Pharm. 2020;17(7):2275–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Zhong H, Chan G, Hu Y, Hu H, Ouyang D. A comprehensive map of FDA-approved pharmaceutical products. Pharmaceutics. 2018;10(4):263.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Zhou Y, Quan G, Wu Q, Zhang X, Niu B, Wu B, et al. Mesoporous silica nanoparticles for drug and gene delivery. Acta Pharmaceutica Sinica B. 2018;8(2):165–77.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Xu B, Li S, Shi R, Liu H. Multifunctional mesoporous silica nanoparticles for biomedical applications. Signal Transduct Target Ther. 2023;8(1):435.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Watermann A, Brieger J. Mesoporous silica nanoparticles as drug delivery vehicles in cancer. Nanomaterials. 2017;7(7):189.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Janßen HC, Angrisani N, Kalies S, Hansmann F, Kietzmann M, Warwas DP, et al. Biodistribution, biocompatibility and targeted accumulation of magnetic nanoporous silica nanoparticles as drug carrier in orthopedics. J Nanobiotechnol. 2020;18(1):14.

    Article  Google Scholar 

  9. Chen W-H, Luo G-F, Lei Q, Cao F-Y, Fan J-X, Qiu W-X, et al. Rational design of multifunctional magnetic mesoporous silica nanoparticle for tumor-targeted magnetic resonance imaging and precise therapy. Biomaterials. 2016;76:87–101.

    Article  CAS  PubMed  Google Scholar 

  10. Lee SB, Lee HW, Darmawan BA, Lee I-K, Cho SJ, Chin J, et al. NIR dye-loaded mesoporous silica nanoparticles for a multifunctional theranostic platform: visualization of tumor and ischemic lesions, and performance of photothermal therapy. J Ind Eng Chem. 2020;88:99–105.

    Article  CAS  Google Scholar 

  11. Phillips E, Penate-Medina O, Zanzonico PB, Carvajal RD, Mohan P, Ye Y, et al. Clinical translation of an ultrasmall inorganic optical-PET imaging nanoparticle probe. Sci Transl Med. 2014;6(260):260ra149-260ra149.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Select Committee on GRAS Substances (SCOGS) Opinion: Silicates. 2015. http://wayback.archive-it.org/7993/20171031063508/https://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/SCOGS/ucm260849.htm.

  13. Janjua TI, Cao Y, Yu C, Popat A. Clinical translation of silica nanoparticles. Nat Rev Mater. 2021;6(12):1072–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Murugadoss S, Lison D, Godderis L, Van Den Brule S, Mast J, Brassinne F, et al. Toxicology of silica nanoparticles: an update. Arch Toxicol. 2017;91(9):2967–3010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Chen L, Liu J, Zhang Y, Zhang G, Kang Y, Chen A, et al. The toxicity of silica nanoparticles to the immune system. Nanomedicine. 2018;13(15):1939–62.

    Article  PubMed  Google Scholar 

  16. Wei Y, Quan L, Zhou C, Zhan Q. Factors relating to the biodistribution & clearance of nanoparticles & their effects on in vivo application. Nanomedicine. 2018;13(12):1495–512.

    Article  CAS  PubMed  Google Scholar 

  17. Jasinski DL, Li H, Guo P. The effect of size and shape of RNA nanoparticles on biodistribution. Mol Ther. 2018;26(3):784–92.

    Article  CAS  PubMed  Google Scholar 

  18. Bagwe RP, Hilliard LR, Tan W. Surface modification of silica nanoparticles to reduce aggregation and nonspecific binding. Langmuir. 2006;22(9):4357–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Dong X, Wu Z, Li X, Xiao L, Yang M, Li Y, et al. The size-dependent cytotoxicity of amorphous silica nanoparticles: a systematic review of in vitro studies. Int J Nanomedicine. 2020;15:9089–113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Wilhelm S, Tavares AJ, Dai Q, Ohta S, Audet J, Dvorak HF, et al. Analysis of nanoparticle delivery to tumours. Nat Rev Mater. 2016;1(5):16014.

    Article  CAS  Google Scholar 

  21. Mirkasymov AB, Zelepukin IV, Nikitin PI, Nikitin MP, Deyev SM. In vivo blockade of mononuclear phagocyte system with solid nanoparticles: efficiency and affecting factors. J Control Release. 2021;330:111–8.

    Article  CAS  PubMed  Google Scholar 

  22. Licciardello N, Hunoldt S, Bergmann R, Singh G, Mamat C, Faramus A, et al. Biodistribution studies of ultrasmall silicon nanoparticles and carbon dots in experimental rats and tumor mice. Nanoscale. 2018;10(21):9880–91.

    Article  CAS  PubMed  Google Scholar 

  23. Ferreira CA, Goel S, Ehlerding EB, Rosenkrans ZT, Jiang D, Sun T, et al. Ultrasmall porous silica nanoparticles with enhanced pharmacokinetics for cancer theranostics. Nano Lett. 2021;21(11):4692–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Xie G, Sun J, Zhong G, Shi L, Zhang D. Biodistribution and toxicity of intravenously administered silica nanoparticles in mice. Arch Toxicol. 2010;84(3):183–90.

    Article  CAS  PubMed  Google Scholar 

  25. Tassinari R, Martinelli A, Valeri M, Maranghi F. Amorphous silica nanoparticles induced spleen and liver toxicity after acute intravenous exposure in male and female rats. Toxicol Ind Health. 2021;37(6):328–35.

    Article  CAS  PubMed  Google Scholar 

  26. Bhavsar D, Patel V, Sawant K. Systematic investigation of in vitro and in vivo safety, toxicity and degradation of mesoporous silica nanoparticles synthesized using commercial sodium silicate. Microporous Mesoporous Mater. 2019;284:343–52.

    Article  CAS  Google Scholar 

  27. Liu T, Li L, Teng X, Huang X, Liu H, Chen D, et al. Single and repeated dose toxicity of mesoporous hollow silica nanoparticles in intravenously exposed mice. Biomaterials. 2011;32(6):1657–68.

    Article  CAS  PubMed  Google Scholar 

  28. Kim I-Y, Joachim E, Choi H, Kim K. Toxicity of silica nanoparticles depends on size, dose, and cell type. Nanomed: Nanotechnol Biol Med. 2015;11(6):1407–16.

    Article  CAS  Google Scholar 

  29. Zhao Y, Wang Y, Ran F, Cui Y, Liu C, Zhao Q, et al. A comparison between sphere and rod nanoparticles regarding their in vivo biological behavior and pharmacokinetics. Sci Rep. 2017;7(1):4131.

    Article  PubMed  PubMed Central  Google Scholar 

  30. MadathiparambilVisalakshan R, González García LE, Benzigar MR, Ghazaryan A, Simon J, Mierczynska-Vasilev A, et al. The influence of nanoparticle shape on protein corona formation. Small. 2020;16(25):2000285.

    Article  CAS  Google Scholar 

  31. Wang W, Gaus K, Tilley RD, Gooding JJ. The impact of nanoparticle shape on cellular internalisation and transport: what do the different analysis methods tell us? Mater Horiz. 2019;6(8):1538–47.

    Article  CAS  Google Scholar 

  32. Wani A, Savithra GHL, Abyad A, Kanvinde S, Li J, Brock S, et al. Surface PEGylation of mesoporous silica nanorods (MSNR): effect on loading, release, and delivery of mitoxantrone in hypoxic cancer cells. Sci Rep. 2017;7(1):2274.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Sargazi S, Laraib U, Barani M, Rahdar A, Fatima I, Bilal M, et al. Recent trends in mesoporous silica nanoparticles of rode-like morphology for cancer theranostics: a review. J Mol Struct. 2022;1261:132922.

    Article  CAS  Google Scholar 

  34. Shao D, Lu M-m, Zhao Y-w, Zhang F, Tan Y-f, Zheng X, et al. The shape effect of magnetic mesoporous silica nanoparticles on endocytosis, biocompatibility and biodistribution. Acta Biomaterialia. 2017;49:531–40.

    Article  CAS  PubMed  Google Scholar 

  35. Fröhlich E. The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles. Int J Nanomedicine. 2012;7:5577–91.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Dogra P, Adolphi NL, Wang Z, Lin Y-S, Butler KS, Durfee PN, et al. Establishing the effects of mesoporous silica nanoparticle properties on in vivo disposition using imaging-based pharmacokinetics. Nat Commun. 2018;9(1):4551.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Lei Q, Guo J, Noureddine A, Wang A, Wuttke S, Brinker CJ, et al. Sol–Gel-based advanced porous silica materials for biomedical applications. Adv Func Mater. 2020;30(41):1909539.

    Article  CAS  Google Scholar 

  38. Bakhshian Nik A, Zare H, Razavi S, Mohammadi H, Torab Ahmadi P, Yazdani N, et al. Smart drug delivery: capping strategies for mesoporous silica nanoparticles. Microporous Mesoporous Mater. 2020;299:110115.

    Article  CAS  Google Scholar 

  39. Mohammadpour R, Cheney DL, Grunberger JW, Yazdimamaghani M, Jedrzkiewicz J, Isaacson KJ, et al. One-year chronic toxicity evaluation of single dose intravenously administered silica nanoparticles in mice and their Ex vivo human hemocompatibility. J Control Release. 2020;324:471–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Yu T, Greish K, McGill LD, Ray A, Ghandehari H. Influence of geometry, porosity, and surface characteristics of silica nanoparticles on acute toxicity: their vasculature effect and tolerance threshold. ACS Nano. 2012;6(3):2289–301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Bindini E, Ramirez MdlA, Rios X, Cossío U, Simó C, Gomez-Vallejo V, et al. In vivo tracking of the degradation of mesoporous silica through 89Zr radio-labeled core–shell nanoparticles. Small. 2021;17(30):2101519.

    Article  CAS  Google Scholar 

  42. Tishchenko VK, Petriev VM, Mikhailovskaya AA, Smoryzanova OA, Kabashin AV, Zavestovskaya IN. Ex vivo biodistribution of gallium-68-labeled porous silicon nanoparticles. J Phys: Conf Ser. 2020;1439(1):012035.

    CAS  Google Scholar 

  43. Peng H, Xu Z, Wang Y, Feng N, Yang W, Tang J. Biomimetic mesoporous silica nanoparticles for enhanced blood circulation and cancer therapy. ACS Appl Bio Mater. 2020;3(11):7849–57.

    Article  CAS  PubMed  Google Scholar 

  44. Yang B, Zhou S, Zeng J, Zhang L, Zhang R, Liang K, et al. Super-assembled core-shell mesoporous silica-metal-phenolic network nanoparticles for combinatorial photothermal therapy and chemotherapy. Nano Res. 2020;13(4):1013–9.

    Article  CAS  Google Scholar 

  45. Castillo RR, Vallet-Regí M. Functional mesoporous silica nanocomposites: biomedical applications and biosafety. Int J Mol Sci. 2019;20(4):929.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Hu Y, Niemeyer CM. Designer DNA–silica/carbon nanotube nanocomposites for traceable and targeted drug delivery. J Mater Chem B. 2020;8(11):2250–5.

    Article  CAS  PubMed  Google Scholar 

  47. Park JH, Jackman JA, Ferhan AR, Belling JN, Mokrzecka N, Weiss PS, et al. Cloaking silica nanoparticles with functional protein coatings for reduced complement activation and cellular uptake. ACS Nano. 2020;14(9):11950–61.

    Article  CAS  PubMed  Google Scholar 

  48. 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;99(Pt A):28–51.

    Article  CAS  PubMed  Google Scholar 

  49. Abdollah MRA, Carter TJ, Jones C, Kalber TL, Rajkumar V, Tolner B, et al. Fucoidan prolongs the circulation time of dextran-coated iron oxide nanoparticles. ACS Nano. 2018;12(2):1156–69.

    Article  CAS  PubMed  Google Scholar 

  50. Sindhwani S, Syed AM, Ngai J, Kingston BR, Maiorino L, Rothschild J, et al. The entry of nanoparticles into solid tumours. Nat Mater. 2020;19(5):566–75.

    Article  CAS  PubMed  Google Scholar 

  51. Adumeau L, Genevois C, Roudier L, Schatz C, Couillaud F, Mornet S. Impact of surface grafting density of PEG macromolecules on dually fluorescent silica nanoparticles used for the in vivo imaging of subcutaneous tumors. Biochim Biophys Acta (BBA) - Gen Subj. 2017;1861(6):1587–96.

    Article  CAS  Google Scholar 

  52. Hayashi Y, Takamiya M, Jensen PB, Ojea-Jiménez I, Claude H, Antony C, et al. Differential nanoparticle sequestration by macrophages and scavenger endothelial cells visualized in vivo in real-time and at ultrastructural resolution. ACS Nano. 2020;14(2):1665–81.

    Article  CAS  PubMed  Google Scholar 

  53. Kramer L, Winter G, Baur B, Kuntz AJ, Kull T, Solbach C, et al. Quantitative and correlative biodistribution analysis of 89Zr-labeled mesoporous silica nanoparticles intravenously injected into tumor-bearing mice. Nanoscale. 2017;9(27):9743–53.

    Article  CAS  PubMed  Google Scholar 

  54. Sudimack J, Lee RJ. Targeted drug delivery via the folate receptor. Adv Drug Deliv Rev. 2000;41(2):147–62.

    Article  CAS  PubMed  Google Scholar 

  55. Zwicke GL, Ali Mansoori G, Jeffery CJ. Utilizing the folate receptor for active targeting of cancer nanotherapeutics. Nano Rev. 2012;3(1):18496.

    Article  CAS  Google Scholar 

  56. Zhang Y, Ye Z, He R, Li Y, Xiong B, Yi M, et al. Bovine serum albumin-based and dual-responsive targeted hollow mesoporous silica nanoparticles for breast cancer therapy. Colloids Surf B. 2023;224:113201.

    Article  CAS  Google Scholar 

  57. Xu X, Wu C, Bai A, Liu X, Lv H, Liu Y. Folate-functionalized mesoporous silica nanoparticles as a liver tumor-targeted drug delivery system to improve the antitumor effect of paclitaxel. J Nanomater. 2017;2017:2069685.

    Article  Google Scholar 

  58. Song Y, Zhou B, Du X, Wang Y, Zhang J, Ai Y, et al. Folic acid (FA)-conjugated mesoporous silica nanoparticles combined with MRP-1 siRNA improves the suppressive effects of myricetin on non-small cell lung cancer (NSCLC). Biomed Pharmacother. 2020;125:109561.

    Article  CAS  PubMed  Google Scholar 

  59. Li Z, Zhang Y, Zhu C, Guo T, Xia Q, Hou X, et al. Folic acid modified lipid-bilayer coated mesoporous silica nanoparticles co-loading paclitaxel and tanshinone IIA for the treatment of acute promyelocytic leukemia. Int J Pharm. 2020;586:119576.

    Article  CAS  PubMed  Google Scholar 

  60. Pochert A, Vernikouskaya I, Pascher F, Rasche V, Lindén M. Cargo-influences on the biodistribution of hollow mesoporous silica nanoparticles as studied by quantitative 19F-magnetic resonance imaging. J Colloid Interface Sci. 2017;488:1–9.

    Article  CAS  PubMed  Google Scholar 

  61. Wang Y, Cheng W, Zhu J, He L, Ren W, Bao D, et al. Programmed Co-delivery of tamoxifen and docetaxel using lipid-coated mesoporous silica nanoparticles for overcoming CYP3A4-mediated resistance in triple-negative breast cancer treatment. Biomed Pharmacother. 2024;170:116084.

    Article  CAS  PubMed  Google Scholar 

  62. Yin H, Yan Q, Liu Y, Yang L, Liu Y, Luo Y, et al. Co-encapsulation of paclitaxel and 5-fluorouracil in folic acid-modified, lipid-encapsulated hollow mesoporous silica nanoparticles for synergistic breast cancer treatment. RSC Adv. 2022;12(50):32534–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Pei W, Cai L, Gong X, Zhang L, Zhang J, Zhu P, et al. Drug-loaded oleic-acid grafted mesoporous silica nanoparticles conjugated with α-lactalbumin resembling BAMLET-like anticancer agent with improved biocompatibility and therapeutic efficacy. Mater Today Bio. 2022;15:100272.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Noureddine A, Marwedel B, Tang L, Medina LY, Serda RE. Specific tumor localization of immunogenic lipid-coated mesoporous silica nanoparticles following intraperitoneal administration in a mouse model of serous epithelial ovarian cancer. Cancers. 2023;15(18):4626.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Maeda H, Nakamura H, Fang J. The EPR effect for macromolecular drug delivery to solid tumors: Improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo. Adv Drug Deliv: Perspect Prospects. 2013;65(1):71–9.

    Article  CAS  Google Scholar 

  66. Kingston BR, Lin ZP, Ouyang B, MacMillan P, Ngai J, Syed AM, et al. Specific endothelial cells govern nanoparticle entry into solid tumors. ACS Nano. 2021;15(9):14080–94.

    Article  CAS  PubMed  Google Scholar 

  67. Maggini L, Cabrera I, Ruiz-Carretero A, Prasetyanto EA, Robinet E, De Cola L. Breakable mesoporous silica nanoparticles for targeted drug delivery. Nanoscale. 2016;8(13):7240–7.

    Article  CAS  PubMed  Google Scholar 

  68. Bansal A, Simon MC. Glutathione metabolism in cancer progression and treatment resistance. J Cell Biol. 2018;217(7):2291–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Kennedy L, Sandhu JK, Harper M-E, Cuperlovic-Culf M. Role of glutathione in cancer: from mechanisms to therapies. Biomolecules. 2020;10(10):1429.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Ding X, Yu W, Wan Y, Yang M, Hua C, Peng N, et al. A pH/ROS-responsive, tumor-targeted drug delivery system based on carboxymethyl chitin gated hollow mesoporous silica nanoparticles for anti-tumor chemotherapy. Carbohyd Polym. 2020;245:116493.

    Article  CAS  Google Scholar 

  71. Benfeitas R, Bidkhori G, Mukhopadhyay B, Klevstig M, Arif M, Zhang C, et al. Characterization of heterogeneous redox responses in hepatocellular carcinoma patients using network analysis. eBioMedicine. 2019;40:471–87.

    Article  PubMed  Google Scholar 

  72. He Y, Shao L, Hu Y, Zhao F, Tan S, He D, et al. Redox and pH dual-responsive biodegradable mesoporous silica nanoparticle as a potential drug carrier for synergistic cancer therapy. Ceram Int. 2021;47(4):4572–8.

    Article  CAS  Google Scholar 

  73. Liu J, Luo Z, Zhang J, Luo T, Zhou J, Zhao X, et al. Hollow mesoporous silica nanoparticles facilitated drug delivery via cascade pH stimuli in tumor microenvironment for tumor therapy. Biomaterials. 2016;83:51–65.

    Article  CAS  PubMed  Google Scholar 

  74. Du L, Liao S, Khatib HA, Stoddart JF, Zink JI. Controlled-access hollow mechanized silica nanocontainers. J Am Chem Soc. 2009;131(42):15136–42.

    Article  CAS  PubMed  Google Scholar 

  75. Qi G, Shi G, Wang S, Hu H, Zhang Z, Yin Q, et al. A novel pH-responsive iron oxide core-shell magnetic mesoporous silica nanoparticle (M-MSN) system encapsulating doxorubicin (DOX) and glucose oxidase (Gox) for pancreatic cancer treatment. Int J Nanomed. 2023;18:7133–47.

    Article  CAS  Google Scholar 

  76. Kumar R, Roy I, Ohulchanskky TY, Vathy LA, Bergey EJ, Sajjad M, et al. In vivo biodistribution and clearance studies using multimodal organically modified silica nanoparticles. ACS Nano. 2010;4(2):699–708.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Zhai W, He C, Wu L, Zhou Y, Chen H, Chang J, et al. Degradation of hollow mesoporous silica nanoparticles in human umbilical vein endothelial cells. J Biomed Mater Res B Appl Biomater. 2012;100B(5):1397–403.

    Article  CAS  Google Scholar 

  78. Morelli C, Maris P, Sisci D, Perrotta E, Brunelli E, Perrotta I, et al. PEG-templated mesoporous silica nanoparticles exclusively target cancer cells. Nanoscale. 2011;3(8):3198–207.

    Article  CAS  PubMed  Google Scholar 

  79. Iversen T-G, Skotland T, Sandvig K. Endocytosis and intracellular transport of nanoparticles: present knowledge and need for future studies. Nano Today. 2011;6(2):176–85.

    Article  CAS  Google Scholar 

  80. Huang X, Li L, Liu T, Hao N, Liu H, Chen D, et al. The shape effect of mesoporous silica nanoparticles on biodistribution, clearance, and biocompatibility in vivo. ACS Nano. 2011;5(7):5390–9.

    Article  CAS  PubMed  Google Scholar 

  81. Lu J, Liong M, Li Z, Zink JI, Tamanoi F. Biocompatibility, biodistribution, and drug-delivery efficiency of mesoporous silica nanoparticles for cancer therapy in animals. Small. 2010;6(16):1794–805.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Lu J, Li Z, Zink JI, Tamanoi F. In vivo tumor suppression efficacy of mesoporous silica nanoparticles-based drug-delivery system: enhanced efficacy by folate modification. Nanomed: Nanotechnol Biol Med. 2012;8(2):212–20.

    Article  CAS  Google Scholar 

  83. Souris JS, Lee C-H, Cheng S-H, Chen C-T, Yang C-S, Ho J-AA, et al. Surface charge-mediated rapid hepatobiliary excretion of mesoporous silica nanoparticles. Biomaterials. 2010;31(21):5564–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Waegeneers N, Brasseur A, Van Doren E, Van der Heyden S, Serreyn P-J, Pussemier L, et al. Short-term biodistribution and clearance of intravenously administered silica nanoparticles. Toxicol Rep. 2018;5:632–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Croissant JG, Brinker CJ. Chapter Eight - Biodegradable silica-based nanoparticles: dissolution kinetics and selective bond cleavage. In: Tamanoi F, editor. The enzymes, vol. 43. Academic Press; 2018. p. 181–214.

    Google Scholar 

  86. Möller K, Bein T. Degradable drug carriers: vanishing mesoporous silica nanoparticles. Chem Mater. 2019;31(12):4364–78.

    Article  Google Scholar 

  87. Cao Y, Li S, Chen J. Modeling better in vitro models for the prediction of nanoparticle toxicity: a review. Toxicol Mech Methods. 2021;31(1):1–17.

    Article  CAS  PubMed  Google Scholar 

  88. Lee K-I, Su C-C, Fang K-M, Wu C-C, Wu C-T, Chen Y-W. Ultrafine silicon dioxide nanoparticles cause lung epithelial cells apoptosis via oxidative stress-activated PI3K/Akt-mediated mitochondria- and endoplasmic reticulum stress-dependent signaling pathways. Sci Rep. 2020;10(1):9928.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Sun M, Zhang J, Liang S, Du Z, Liu J, Sun Z, et al. Metabolomic characteristics of hepatotoxicity in rats induced by silica nanoparticles. Ecotoxicol Environ Saf. 2021;208:111496.

    Article  CAS  PubMed  Google Scholar 

  90. Wang D-P, Wang Z-J, Zhao R, Lin C-X, Sun Q-Y, Yan C-P, et al. Silica nanomaterials induce organ injuries by Ca2+-ROS-initiated disruption of the endothelial barrier and triggering intravascular coagulation. Part Fibre Toxicol. 2020;17(1):12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Hozayen WG, Mahmoud AM, Desouky EM, El-Nahass E-S, Soliman HA, Farghali AA. Cardiac and pulmonary toxicity of mesoporous silica nanoparticles is associated with excessive ROS production and redox imbalance in Wistar rats. Biomed Pharmacother. 2019;109:2527–38.

    Article  CAS  PubMed  Google Scholar 

  92. Yang X, Feng L, Zhang Y, Hu H, Shi Y, Liang S, et al. Co-exposure of silica nanoparticles and methylmercury induced cardiac toxicity in vitro and in vivo. Sci Total Environ. 2018;631–632:811–21.

    Article  PubMed  Google Scholar 

  93. Ma R, Qi Y, Zhao X, Li X, Sun X, Niu P, et al. Amorphous silica nanoparticles accelerated atherosclerotic lesion progression in ApoE−/− mice through endoplasmic reticulum stress-mediated CD36 up-regulation in macrophage. Part Fibre Toxicol. 2020;17(1):50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Liu Y-Q, Xue S-M, Zhang P, Xu L-N, Wang D-P, Li G, et al. Silica nanoparticles disturb ion channels and transmembrane potentials of cardiomyocytes and induce lethal arrhythmias in mice. Int J Nanomedicine. 2020;15:7397–413.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Yu Y, Zhu T, Li Y, Jing L, Yang M, Li Y, et al. Repeated intravenous administration of silica nanoparticles induces pulmonary inflammation and collagen accumulation via JAK2/STAT3 and TGF-β/Smad3 pathways in vivo. Int J Nanomedicine. 2019;14:7237–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Parveen A, Rizvi SH, Sushma, Mahdi F, Ahmad I, Singh PP, et al. Intranasal exposure to silica nanoparticles induces alterations in pro-inflammatory environment of rat brain. Toxicol Ind Health. 2017;33(2):119–32.

    Article  CAS  PubMed  Google Scholar 

  97. Chou C-C, Chen W, Hung Y, Mou C-Y. Molecular elucidation of biological response to mesoporous silica nanoparticles in vitro and in vivo. ACS Appl Mater Interfaces. 2017;9(27):22235–51.

    Article  CAS  PubMed  Google Scholar 

  98. Liu Y, Wei H, Tang J, Yuan J, Wu M, Yao C, et al. Dysfunction of pulmonary epithelial tight junction induced by silicon dioxide nanoparticles via the ROS/ERK pathway and protein degradation. Chemosphere. 2020;255:126954.

    Article  CAS  PubMed  Google Scholar 

  99. Inoue M, Sakamoto K, Suzuki A, Nakai S, Ando A, Shiraki Y, et al. Size and surface modification of silica nanoparticles affect the severity of lung toxicity by modulating endosomal ROS generation in macrophages. Part Fibre Toxicol. 2021;18(1):1–20.

    Article  Google Scholar 

  100. Zhang X, Luan J, Chen W, Fan J, Nan Y, Wang Y, et al. Mesoporous silica nanoparticles induced hepatotoxicity via NLRP3 inflammasome activation and caspase-1-dependent pyroptosis. Nanoscale. 2018;10(19):9141–52.

    Article  CAS  PubMed  Google Scholar 

  101. Magaye RR, Yue X, Zou B, Shi H, Yu H, Liu K, et al. Acute toxicity of nickel nanoparticles in rats after intravenous injection. Int J Nanomedicine. 2014;9:1393–402.

    PubMed  PubMed Central  Google Scholar 

  102. Guo C, Liu Y, Li Y. Adverse effects of amorphous silica nanoparticles: focus on human cardiovascular health. J Hazard Mater. 2021;406:124626.

    Article  CAS  PubMed  Google Scholar 

  103. Aouey B, Boukholda K, Gargouri B, Bhatia HS, Attaai A, Kebieche M, et al. Silica nanoparticles induce hepatotoxicity by triggering oxidative damage, apoptosis, and Bax-Bcl2 signaling pathway. Biol Trace Elem Res. 2021;200(4):1688–98.

    Article  PubMed  Google Scholar 

  104. Lozano O, Silva-Platas C, Chapoy-Villanueva H, Pérez BE, Lees JG, Ramachandra CJA, et al. Amorphous SiO2 nanoparticles promote cardiac dysfunction via the opening of the mitochondrial permeability transition pore in rat heart and human cardiomyocytes. Part Fibre Toxicol. 2020;17(1):15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Deng Y-D, Zhang X-D, Yang X-S, Huang Z-L, Wei X, Yang X-F, et al. Subacute toxicity of mesoporous silica nanoparticles to the intestinal tract and the underlying mechanism. J Hazard Mater. 2021;409:124502.

    Article  CAS  PubMed  Google Scholar 

  106. Berry JP, Arnoux B, Stanislas G, Galle P, Chretien J. A microanalytic study of particles transport across the alveoli: role of blood platelets. Biomedicine / [publiee pour l’AAICIG]. 1977;27(9–10):354–7.

    CAS  Google Scholar 

  107. Nemmar A, Hoet PH, Vanquickenborne B, Dinsdale D, Thomeer M, Hoylaerts MF, et al. Passage of inhaled particles into the blood circulation in humans. Circulation. 2002;105(4):411–4.

    Article  CAS  PubMed  Google Scholar 

  108. Oberdörster G, Oberdörster E, Oberdörster J. Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect. 2005;113(7):823–39.

    Article  PubMed  PubMed Central  Google Scholar 

  109. Mohamed IN, Sheibani N, El-Remessy AB. Deletion of thioredoxin-interacting protein (TXNIP) abrogates high fat diet-induced retinal leukostasis, barrier dysfunction and microvascular degeneration in a mouse obesity model. Int J Mol Sci. 2020;21(11):3983.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Wang M, Li J, Dong S, Cai X, Simaiti A, Yang X, et al. Silica nanoparticles induce lung inflammation in mice via ROS/PARP/TRPM2 signaling-mediated lysosome impairment and autophagy dysfunction. Part Fibre Toxicol. 2020;17(1):23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Van Rijt SH, Bölükbas DA, Argyo C, Wipplinger K, Naureen M, Datz S, et al. Applicability of avidin protein coated mesoporous silica nanoparticles as drug carriers in the lung. Nanoscale. 2016;8(15):8058–69.

    Article  PubMed  Google Scholar 

  112. Wottrich R, Diabaté S, Krug HF. Biological effects of ultrafine model particles in human macrophages and epithelial cells in mono-and co-culture. Int J Hyg Environ Health. 2004;207(4):353–61.

    Article  CAS  PubMed  Google Scholar 

  113. Mohammadpour R, Yazdimamaghani M, Cheney DL, Jedrzkiewicz J, Ghandehari H. Subchronic toxicity of silica nanoparticles as a function of size and porosity. J Control Release. 2019;304:216–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Duan J, Yu Y, Li Y, Yu Y, Li Y, Zhou X, et al. Toxic effect of silica nanoparticles on endothelial cells through DNA damage response via Chk1-dependent G2/M checkpoint. PLoS ONE. 2013;8(4):e62087.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Bauer AT, Strozyk EA, Gorzelanny C, Westerhausen C, Desch A, Schneider MF, et al. Cytotoxicity of silica nanoparticles through exocytosis of von Willebrand factor and necrotic cell death in primary human endothelial cells. Biomaterials. 2011;32(33):8385–93.

    Article  CAS  PubMed  Google Scholar 

  116. Yazdimamaghani M, Moos PJ, Dobrovolskaia MA, Ghandehari H. Genotoxicity of amorphous silica nanoparticles: status and prospects. Nanomed Nanotechnol Biol Med. 2019;16:106–25.

    Article  CAS  Google Scholar 

  117. Kharlamov AN, Feinstein JA, Cramer JA, Boothroyd JA, Shishkina EV, Shur V. Plasmonic photothermal therapy of atherosclerosis with nanoparticles: long-term outcomes and safety in NANOM-FIM trial. Future Cardiol. 2017;13(4):345–63.

    Article  CAS  PubMed  Google Scholar 

  118. Rastinehad AR, Anastos H, Wajswol E, Winoker JS, Sfakianos JP, Doppalapudi SK, et al. Gold nanoshell-localized photothermal ablation of prostate tumors in a clinical pilot device study. Proc Natl Acad Sci. 2019;116(37):18590–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Phillips E, Penate-Medina O, Zanzonico PB, Carvajal RD, Mohan P, Ye Y, et al. Clinical translation of an ultrasmall inorganic optical-PET imaging nanoparticle probe. Sci Transl Med. 2014;6(260):260ra149.

    Article  PubMed  PubMed Central  Google Scholar 

  120. Zanoni DK, Stambuk HE, Madajewski B, Montero PH, Matsuura D, Busam KJ, et al. Use of ultrasmall core-shell fluorescent silica nanoparticles for image-guided sentinel lymph node biopsy in head and neck melanoma: a nonrandomized clinical trial. JAMA Netw Open. 2021;4(3):e211936-e.

    Article  Google Scholar 

  121. Hargrove D, Liang B, Kashfi-Sadabad R, Joshi GN, Gonzalez-Fajardo L, Glass S, et al. Tumor-mesoporous silica nanoparticle interactions following intraperitoneal delivery for targeting peritoneal metastasis. J Control Release: Off J Control Release Soc. 2020;328:846–58.

    Article  CAS  Google Scholar 

  122. Di Pasqua AJ, Yuan H, Chung Y, Kim JK, Huckle JE, Li C, et al. Neutron-activatable holmium-containing mesoporous silica nanoparticles as a potential radionuclide therapeutic agent for ovarian cancer. J Nucl Med: Off Publ Soc Nucl Med. 2013;54(1):111–6.

    Article  Google Scholar 

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Acknowledgements

The authors would like to acknowledge Dr. Derek Hargrove for his valuable insights on the manuscript.

Funding

We appreciate the financial support from the National Cancer Institute of the National Institutes of Health R41CA239989, R44CA239989, and the Research Scholar Grant RSG-15–011-01-CDD from the American Cancer Society.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut, USA

    Joshua Yu, Nirnoy Dan, Seyyed Majid Eslami & Xiuling Lu

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  1. Joshua Yu
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  2. Nirnoy Dan
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  4. Xiuling Lu
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Contributions

Joshua Yu: conceptualization, literature review, and writing—original draft. Nirnoy Dan: conceptualization, literature review, and writing—original draft discussion. Seyyed Majid Eslami: writing—review and editing. Xiuling Lu: conceptualization, supervision, and writing—review and editing.

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Correspondence to Xiuling Lu.

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Conflict of Interest

Dr. Xiuling Lu is an inventor of intellectual property licensed to Nami Therapeutics Corp for developing silica nanoparticle-based radiopharmaceuticals. Dr. Xiuling Lu owns equity. It is important to note that the analysis and interpretation in this review were without any influence from the potential financial gains. The authors affirm that the conclusions drawn and the information provided in this paper are based on scientific evidence.

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Communicated by Aliasger Salem

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Yu, J., Dan, N., Eslami, S.M. et al. State of the Art of Silica Nanoparticles: An Overview on Biodistribution and Preclinical Toxicity Studies. AAPS J 26, 35 (2024). https://doi.org/10.1208/s12248-024-00906-w

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