Silicon-containing nanocarriers for targeted drug delivery: synthesis, physicochemical properties and acute toxicity

Figures & data

Figure 1. Surface modification of SiO₂NPs. (a) Scheme of synthesis of aminated silica; (b) surface modification of aminated SiO₂NPs with succinic anhydride to form a carboxylic acid terminus; (c) the binding reaction of glutardialdehyde with amino groups on silica nanoparticles is shown.

Figure 2. Synthesis of OrSiO₂NPs with a silica core. (a) Scheme of the synthesis of the OrSiO₂NPs; (b and c) scheme of synthesis SiO₂ + OrSiO₂NPs.

Figure 3. Diagram of the synthesis of SSiO₂NPs.

Figure 4. Distribution of nano-objects by size. (a) Primary OrSiO₂NPs (OrSiO₂NPs³), (b) OrSiO₂NPs obtained after condensation (OrSiO₂NPs¹⁵⁰); (c) SiO₂ + OrSiO₂NPs; (d) SSiO₂NPs.

Table 1. The average size of nano-objects.

	SiO2NPs	OrSiO2NPs^3	OrSiO2NPs^150	SiO2 + OrSiO2NPs	SSiO2NPs
Size, nm	7–10	3	150	75	196

SiO₂NPs, silica nanoparticles; OrSiO₂NPs, organomodified silica nanoparticles; SiO₂ + OrSiO₂NPs, OrSiO₂NPs with SiO₂ core; SSiO₂NPs, sulfonated silica nanoparticles.

Figure 5. IR spectra of silicon-containing NPs. (a) IR spectra of (1) SiO₂NPs, (2) aminated SiO₂NPs, and (3) SiO₂ + OrSiO₂NPs; (b) IR spectra of (1) SiO₂NPs, (2) OrSiO₂NPs, and (3) SSiO₂NPs.

Figure 6. The kinetics of adenosine desorption from the surface of the silica. (a) The relation between adenosine release into the suspension of SiO₂NPs and time for different immobilization methods: (1) adsorption (unmodified SiO₂NPs); (2) covalent bonding (glutaraldehyde-modified SiO₂NPs); (3) coordination-ion bonding (succinic anhydride-treated SiO₂NPs); (b) the relation between adenosine concentration in the suspension of SSiO₂NPs versus time.

Figure 7. Bioelimination of OrSiO₂NPs. (a and b) The silicon content after intravenous administration of OrSiO₂NPs³. (c and d) The silicon content after intravenous administration of OrSiO₂NPs¹⁵⁰.

Table 2. The effect of intravenous administration of Si-containing nanoparticles on hemodynamic parameters in rats.

	OrSiO2NPs^3	OrSiO2NPs^150	SiO2 + OrSiO2NPs	SiO2NPs	SSiO2NPs
Mean blood pressure, mm Hg
Before infusion	115 ± 12	121 ± 15	110 ± 17	102 ± 21	113 ± 18
5 min infusion	118 ± 14	116 ± 17	114 ± 22	104 ± 20	115 ± 23
10 min infusion	105 ± 13	108 ± 15	117 ± 28	108 ± 21	121 ± 26
5 min after infusion	117 ± 14	105 ± 11	115 ± 25	108 ± 18	119 ± 22
Heart rate, beats/min
Before infusion	416 ± 25	421 ± 25	403 ± 31	385 ± 43	398 ± 38
5 min infusion	410 ± 31	406 ± 28	395 ± 40	379 ± 35	396 ± 42
10 min infusion	405 ± 33	412 ± 34	399 ± 36	368 ± 32	384 ± 45
5 min after infusion	396 ± 19	398 ± 29	382 ± 42	354 ± 28	371 ± 33

SiO₂NPs, silica nanoparticles; OrSiO₂NPs³, organomodified silica nanoparticles with mean diameter of 3 nm; OrSiO₂NPs¹⁵⁰, organomodified silica nanoparticles with a mean diameter of 150 nm; SiO₂+OrSiO₂NPs, OrSiO₂NPs with SiO₂ core; SSiO₂NPs, sulfonated silica nanoparticles. Values are means ± SD.

Figure 8. Hemodynamic response to free and SiO₂ + OrSiO₂NP-bound adenosine. Adsorption of adenosine on SiO₂ + OrSiO₂NPs resulted in the slow release of adenosine and reduction of side effects in the form of a sharp drop in arterial pressure. (a) Infusion of free adenosine and (b) infusion of SiO₂ + OrSiO₂NPs loaded with adenosine.

Table 3. The effect of intravenous administration of adenosine-loaded SiO₂+OrSiO₂NPs on hemodynamic parameters in rats.

	ADO 300 μg/kg×min			SiO2 + OrSiO2 NPs + ADO 300 μg/kg × min
	Baseline	The first minute	The fifth minute	Baseline	The first minute	The fifth minute
MAP	149 ± 12	92 ± 19	113 ± 9	145 ± 12	126 ± 25	108 ± 20
HR	421 ± 12	362 ± 26	370 ± 18	411 ± 17	389 ± 21	384 ± 25

HR, heart rate; MAP, mean arterial pressure; ADO, adenosine; SiO₂+OrSiO₂NPs, organomodified silica nanoparticles with a silica core. Values are means ± SD.