Sol‒gel synthesis, properties and protein loading/delivery capacity of hollow bioactive glass nanospheres with large hollow cavity and mesoporous shell

Abstract

Hollow nanospheres exhibit unique properties and find a wide interest in several potential applications such as drug delivery. Herein, novel hollow bioactive glass nanospheres (HBGn) with large hollow cavity and large mesopores in their outer shells were synthesized by a simple and facile one-pot ultrasound assisted sol‒gel method using PEG as the core soft-template. Interestingly, the produced HBGn exhibited large hollow cavity with ~43 nm in diameter and mesoporous shell of ~37 nm in thickness and 7 nm pore size along with nanosphere size around 117 nm. XPS confirmed the presence of Si and Ca elements at the surface of the HBGn outer shell. Notably, HBGn showed high protein loading capacity (~570 mg of Cyto c per 1 g of HBGn) in addition to controlled protein release over 5 d. HBGn also demonstrated a good in vitro capability of releasing calcium (Ca²⁺: 170 ppm) and silicate (SiO₄⁴⁻: 78 ppm) ions in an aqueous medium over 2 weeks under physiological-like conditions. Excellent in vitro growth of bone-like hydroxyapatite nanocrystals was exhibited by HBGn during the soaking in SBF. A possible underlying mechanism involving the formation of spherical aggregates (coils) of PEG was proposed for the formation process of HBGn.

Graphical abstract

Keywords

bioactive glass / hollow nanosphere / hollow cavity / mesoporous shell / soft-template ultrasound assisted sol‒gel synthesis / therapeutic protein delivery

References

[1] Deodhar G V, Adams M L, Trewyn B G . Controlled release and intracellular protein delivery from mesoporous silica nanoparticles. Biotechnology Journal, 2017, 12( 1): 1600408

[2] Leader B, Baca Q J, Golan D E . Protein therapeutics: a summary and pharmacological classification. Nature Reviews Drug Discovery, 2008, 7( 1): 21– 39

[3] Guziewicz N, Best A, Perez-Ramirez B, , . Lyophilized silk fibroin hydrogels for the sustained local delivery of therapeutic monoclonal antibodies. Biomaterials, 2011, 32( 10): 2642– 2650

[4] Yasun E, Gandhi S, Choudhury S, , . Hollow micro and nanostructures for therapeutic and imaging applications. Journal of Drug Delivery Science and Technology, 2020, 60 : 102094

[5] Vargason A M, Anselmo A C, Mitragotri S . The evolution of commercial drug delivery technologies. Nature Biomedical Engineering, 2021, 5( 9): 951– 967

[6] Xu C, Lei C, Yu C . Mesoporous silica nanoparticles for protein protection and delivery. Frontiers in Chemistry, 2019, 7 : 290

[7] Raman V, Van Dessel N, Hall C L, , . Intracellular delivery of protein drugs with an autonomously lysing bacterial system reduces tumor growth and metastases. Nature Communications, 2021, 12( 1): 6116

[8] Ray M, Lee Y W, Scaletti F, , . Intracellular delivery of proteins by nanocarriers. Nanomedicine, 2017, 12( 8): 941– 952

[9] Zhao D, Yang N, Xu L, , . Hollow structures as drug carriers: recognition, response, and release. Nano Research, 2022, 15( 2): 739– 757

[10] Fu Z, Zhou Q, Li L, , . Preparation of hollow silica nanoparticles using cationic spherical polyelectrolyte brushes as catalytic template. Colloid & Polymer Science, 2020, 298( 7): 879– 886

[11] Sharma J, Polizos G . Hollow silica particles: recent progress and future perspectives. Nanomaterials, 2020, 10( 8): 1599

[12] Zhu Y, Zhang M, Wei S, , . Temperature-responsive P(NIPAM-co-NHMA)-grafted organic-inorganic hybrid hollow mesoporous silica nanoparticles for controlled drug delivery. Journal of Drug Delivery Science and Technology, 2022, 70 : 103197

[13] Li B, Zeng H C . Architecture and preparation of hollow catalytic devices. Advanced Materials, 2019, 31( 38): 1801104

[14] Bao Y, Shi C, Wang T, , . Recent progress in hollow silica: template synthesis, morphologies and applications. Microporous and Mesoporous Materials, 2016, 227 : 121– 136

[15] Wu X, Wei M, Yu S, , . Formation of cerium oxide hollow spheres and investigation of hollowing mechanism. SN Applied Sciences, 2019, 1( 2): 170

[16] El Mel A A, Nakamura R, Bittencourt C . The Kirkendall effect and nanoscience: hollow nanospheres and nanotubes. Beilstein Journal of Nanotechnology, 2015, 6 : 1348– 1361

[17] Fan H J, Gösele U, Zacharias M . Formation of nanotubes and hollow nanoparticles based on Kirkendall and diffusion processes: a review. Small, 2007, 3( 10): 1660– 1671

[18] Soares S F, Fernandes T, Daniel-da-Silva A L, , . The controlled synthesis of complex hollow nanostructures and prospective applications. Proceedings A: Mathematical, Physical and Engineering Sciences, 2019, 475( 2224): 20180677

[19] Mutlu N, Beltrán AM, Nawaz Q, , . Combination of selective etching and impregnation toward hollow mesoporous bioactive glass nanoparticles. Nanomaterials, 2021, 11( 7): 1846

[20] Li B, Luo W, Wang Y, , . Bioactive SiO₂–CaO–P₂O₅ hollow nanospheres for drug delivery. Journal of Non-Crystalline Solids, 2016, 447 : 98– 103

[21] Pappas G S, Bilalis P, Kordas G C . Synthesis and characterization of SiO₂–CaO–P₂O₅ hollow nanospheres for biomedical applications. Materials Letters, 2012, 67( 1): 273– 276

[22] Liu T, Li Z, Ding X, , . Facile synthesis of hollow bioactive glass nanospheres with tunable size. Materials Letters, 2017, 190 : 99– 102

[23] Wang X, Miao X, Li Z, , . Fabrication of mesoporous silica hollow spheres using triblock copolymer PEG–PPG–PEG as template. Journal of Non-Crystalline Solids, 2010, 356( 18‒19): 898– 905

[24] Abdollahi S N, Naderi M, Amoabediny G . Synthesis and characterization of hollow gold nanoparticles using silica spheres as templates. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2013, 436 : 1069– 1075

[25] Xie Y, Kocaefe D, Chen C, , . Review of research on template methods in preparation of nanomaterials. Journal of Nanomaterials, 2016, 2016 : 2302595

[26] Son S J, Bai X, Lee S B. Inorganic hollow nanoparticles and nanotubes in nanomedicine Part 1. Drug/gene delivery applications. Drug Discovery Today, 2007, 12( 15–16): 650– 656

[27] Mai Z, Chen J, Cao Q, , . Rational design of hollow mesoporous titania nanoparticles loaded with curcumin for UV-controlled release and targeted drug delivery. Nanotechnology, 2021, 32( 20): 205604

[28] Lin K, Gan Y, Zhu P, , . Hollow mesoporous polydopamine nanospheres: synthesis, biocompatibility and drug delivery. Nanotechnology, 2021, 32( 28): 285602

[29] Xue J, Zheng W, Wang L, , . Scalable fabrication of polydopamine nanotubes based on curcumin crystals. ACS Biomaterials Science & Engineering, 2016, 2( 4): 489– 493

[30] Teng Z, Li W, Tang Y, , . Mesoporous organosilica hollow nanoparticles: synthesis and applications. Advanced Materials, 2019, 31( 38): 1707612

[31] Lin C Y, Li W P, Huang S P, , . Hollow mesoporous silica nanosphere-supported FePt nanoparticles for potential theranostic applications. Journal of Materials Chemistry B: Materials for Biology and Medicine, 2017, 5( 36): 7598– 7607

[32] Kong M, Tang J, Qiao Q, , . Biodegradable hollow mesoporous silica nanoparticles for regulating tumor microenvironment and enhancing antitumor efficiency. Theranostics, 2017, 7( 13): 3276– 3292

[33] Migneco C, Fiume E, Verné E, , . A guided walk through the world of mesoporous bioactive glasses (MBGs): fundamentals, processing, and applications. Nanomaterials, 2020, 10( 12): 2571

[34] Kapp M, Li C, Xu Z, , . Protein adsorption on SiO₂‒CaO bioactive glass nanoparticles with controllable Ca content. Nanomaterials, 2021, 11( 3): 561

[35] El-Fiqi A, Kim H W . Sol‒gel synthesis and characterization of novel cobalt ions-containing mesoporous bioactive glass nanospheres as hypoxia and ferroptosis-inducing nano-therapeutics. Journal of Non-Crystalline Solids, 2021, 569 : 120999

[36] Hu Q, Li Y, Zhao N, , . Facile synthesis of hollow mesoporous bioactive glass sub-micron spheres with a tunable cavity size. Materials Letters, 2014, 134 : 130– 133

[37] Wang Y, Chen X . Facile synthesis of hollow mesoporous bioactive glasses with tunable shell thickness and good monodispersity by micro-emulsion method. Materials Letters, 2017, 189 : 325– 328

[38] Wang Y, Pan H, Chen X . The preparation of hollow mesoporous bioglass nanoparticles with excellent drug delivery capacity for bone tissue regeneration. Frontiers in Chemistry, 2019, 7 : 283

[39] Kokubo T, Takadama H . How useful is SBF in predicting in vivo bone bioactivity?. Biomaterials, 2006, 27( 15): 2907– 2915

[40] El-Fiqi A, Allam R, Kim H W . Antioxidant cerium ions-containing mesoporous bioactive glass ultrasmall nanoparticles: structural, physico-chemical, catalase-mimic and biological properties. Colloids and Surfaces B: Biointerfaces, 2021, 206 : 111932

[41] El-Fiqi A, Mandakhbayar N, Jo S B, , . Nanotherapeutics for regeneration of degenerated tissue infected by bacteria through the multiple delivery of bioactive ions and growth factor with antibacterial/angiogenic and osteogenic/odontogenic capacity. Bioactive Materials, 2021, 6( 1): 123– 136

[42] Mudalige T, Qu H, Van Haute D, , . Chapter 11 — Characterization of nanomaterials: tools and challenges. In: López Rubio A, Fabra Rovira M J, Martinez Sans M, et al., eds. Nanomaterials for Food Applications. Amsterdam, Netherlands: Elsevier, 2019, 313– 353

[43] El-Fiqi A, Kim J H, Kim H W . Novel bone-mimetic nanohydroxyapatite/collagen porous scaffolds biomimetically mineralized from surface silanized mesoporous nanobioglass/collagen hybrid scaffold: physicochemical, mechanical and in vivo evaluations. Materials Science and Engineering C, 2020, 110 : 110660

[44] El-Fiqi A, Buitrago J O, Yang S H, , . Biomimetically grown apatite spheres from aggregated bioglass nanoparticles with ultrahigh porosity and surface area imply potential drug delivery and cell engineering applications. Acta Biomaterialia, 2017, 60 : 38– 49

[45] El-Fiqi A, Kim H W . Nano/micro-structured poly(ε-caprolactone)/gelatin nanofibers with biomimetically-grown hydroxyapatite spherules: high protein adsorption, controlled protein delivery and sustained bioactive ions release designed as a multifunctional bone regenerative membrane. Ceramics International, 2021, 47( 14): 19873– 19885

[46] Soulet F, Al Saati T, Roga S, , . Fibroblast growth factor-2 interacts with free ribosomal protein S19. Biochemical and Biophysical Research Communications, 2001, 289( 2): 591– 596

[47] Slowing I I, Trewyn B G, Lin V S Y . Mesoporous silica nanoparticles for intracellular delivery of membrane-impermeable proteins. Journal of the American Chemical Society, 2007, 129( 28): 8845– 8849

[48] Li B, Zhao Y, Xu X, , . Fabrication of hollow Sb₂O₃ microspheres by PEG coil template. Chemistry Letters, 2006, 35( 9): 1026– 1027

[49] Azri A, Giamarchi P, Grohens Y, , . Polyethylene glycol aggregates in water formed through hydrophobic helical structures. Journal of Colloid and Interface Science, 2012, 379( 1): 14– 19

[50] Israelachvili J . The different faces of poly(ethylene glycol). Proceedings of the National Academy of Sciences of the United States of America, 1997, 94( 16): 8378– 8379

[51] Xu Y, Jiao X, Chen D . Peg-assisted preparation of single-crystalline Cu₂O hollow nanocubes. The Journal of Physical Chemistry C, 2008, 112( 43): 16769– 16773

[52] Xu Y, Chen D, Jiao X, , . Nanosized Cu₂O/PEG400 composite hollow spheres with mesoporous shells. The Journal of Physical Chemistry C, 2007, 111( 44): 16284– 16289

[53] Cui Y, Liu L, Li B, , . Fabrication of tunable core‒shell structured TiO₂ mesoporous microspheres using linear polymer polyethylene glycol as templates. The Journal of Physical Chemistry C, 2010, 114( 6): 2434– 2439

[54] Zhou X, Chen S, Zhang D, , . Microsphere organization of nanorods directed by PEG linear polymer. Langmuir, 2006, 22( 4): 1383– 1387

[55] Rao J, Yu A, Shao C, , . Construction of hollow and mesoporous ZnO microsphere: a facile synthesis and sensing property. ACS Applied Materials & Interfaces, 2012, 4( 10): 5346– 5352

[56] Dhas N A, Suslick K S . Sonochemical preparation of hollow nanospheres and hollow nanocrystals. Journal of the American Chemical Society, 2005, 127( 8): 2368– 2369

[57] Bang J H, Suslick K S . Sonochemical synthesis of nanosized hollow hematite. Journal of the American Chemical Society, 2007, 129( 8): 2242– 2243

[58] Xu H, Zeiger B W, Suslick K S . Sonochemical synthesis of nanomaterials. Chemical Society Reviews, 2013, 42( 7): 2555– 2567

[59] Zhang M, Chang J . Surfactant-assisted sonochemical synthesis of hollow calcium silicate hydrate (CSH) microspheres for drug delivery. Ultrasonics Sonochemistry, 2010, 17( 5): 789– 792

Electronic supplementary information

Supplementary materials can be found in the online version at https://doi.org/10.1007/s11706-022-0608-6, which are associated with this work including Table S1 and Fig. S1.

RIGHTS & PERMISSIONS

2022 Higher Education Press