Responsive mesoporous silica nanocarriers in glioma therapy: A step forward in overcoming biological barriers

Table 1 Summary of studies investigating mesoporous silica nanoparticles for blood-brain barrier penetration

Ref.	Design	MSN size	Cargo	Surface modifications	Transport of MSNs	Primary findings
Chen et al[120]	Zebrafish model and cell culture	50, 200 nm	Doxorubicin	PEG; TMAC	Protein corona-mediated transcytosis	Negatively charged (approximately -40 mV), 50 nm MSNs were shown to cross the BBB via a protein corona-mediated mechanism involving afamin, basigin, and ApoE
Baghirov et al[122]	In vitro BBB model and in vivo mouse imaging	50 (spherical), 300 approximately 100 nm (rod)	--	PEG-PEI copolymer	Transcellular (transcytosis)	PEG-PEI enhanced cellular uptake, and MSNs were detectable in brain vasculature with low cytotoxicity
Shadmani et al[125]	In vitro and in vivo	Approximately 50 nm	Methotrexate	TAT peptide	Energy-dependent endocytosis (expected)	TAT-functionalized MSNs improved methotrexate delivery, increasing the brain-to-plasma ratio
Mo et al[38]	In vitro	40 nm	Doxorubicin	PEI-cRGD peptide	Integrin receptor-mediated	cRGD-conjugated MSNs show enhanced BBB penetration and glioblastoma targeting
Bouchoucha et al[121]	In vitro and in vivo	50, 160 nm	Gd-chelate (MRI contrast agent)	PEG; Ri7 antibody; Gd chelate	Receptor-mediated (antibody)	Ri7-MSNs (50 nm) had targeted brain endothelium, were MRI-visible, and showed in vivo brain accumulation
Shevtsov et al[110]	In vitro and in vivo (Wistar rat glioma model)	100 to 150 nm × 250 nm (length)	Fe (0) (Core)	--	--	Fe-loaded MSNs accumulated in glioma and showed a dose-dependent toxicity
Orlando et al[153]	In vitro and ex vivo	30, 250 nm	--	APTES modified (MSN-NH2)	Size/protein corona-dependent	MSNs showed size-dependent toxicity, with 30 nm particles being less toxic, and protein corona exerted a key role in modulating cell interactions

ApoE: Apolipoprotein E; BBB: Blood-brain barrier; cRGD: Cyclic arginine-glycine-aspartic acid; Gd: Gadolinium; MSNs: Mesoporous silica nanoparticles; PEG: Polyethylene glycol; PEI: Polyethyleneimine; TAT: Trans-activator of transcription; TMAC: Trimethylammonium chloride; MSN-SH: MSNs with sulfhydryl groups; MRI: Magnetic resonance imaging.

Table 2 Physical properties and hemolytic activity

Ref.	Factors affecting hemolysis	Hemolysis range	Key findings
Yu et al[137]	Size, shape, porosity	10-500 (significant hemolysis at high doses)	Porosity and shape affected hemolysis
Paula et al[138]	Size, pore, surface charge	--	Protein corona and positive charge lowered hemolysis
Joglekar et al[148]	Morphology (spherical/tubular)	Minimal up to 500 µg/mL	Spherical MSNs showed lower hemolysis
Martínez-Carmona et al[165]	Protein interaction	EC50: 8-28 µg/mL (protein-dependent)	Protein corona suppressed hemolysis dose-dependently
Yildirim et al[176]	Surface functionalization with ionic, polar, neutral, and hydrophobic groups	Approximately 100-500 µg/mL	Functionalization with ionic groups reduced hemolysis

MSN: Mesoporous silica nanoparticle.