In the last decade, there has been a consistent increase in tumor incidence, presenting a substantial threat to human health and survival[1]. Although chemotherapy remains the primary treatment approach for cancer, its effectiveness has been hindered by significant side effects. Common challenges include the low water solubility of anticancer drugs, short circulation time in the bloodstream, severe adverse reactions, lack of treatment selectivity, and restricted tissue penetration[2-4]. In recent years, there has been a growing interest in developing multifunctional nano-drug carriers to overcome the limitations associated with traditional chemotherapy, such as nonselective drug delivery, low cell uptake efficiency, and side effects[5-6]. Among these carriers, mesoporous silicon nanoparticles (MSNs) offer various advantages as drug carriers, including the ability to adapt to different particle shapes, adjustable pore size, high specific surface area, ease of surface modification, and excellent biocompatibility[7-11]. Consequently, MSNs have emerged as promising candidates for various applications, including molecular imaging[12], catalysis[13], separation[14], and drug delivery[15]. For instance, Zeng et al. demonstrated a simple drug-self-gated strategy for mesoporous silica nanocarriers[16]. Despite these advantages, MSNs still face challenges such as poor degradability and lack of targeted drug delivery properties[10, 17]. A hybrid silica carrier with disulfide bonds doped into the Si-O-Si framework offers rapid redox- responsive biodegradation and effective controlled release performance, which can address these challenges[18-19].
"Intelligent" nanoparticles provide new possibilities for cancer treatment to enable controlled drug release. Particularly, pH-responsive gated nanomaterial carriers offer the capability to release drugs effectively and in a controlled manner[20]. However, the current pH-responsive and gated MSN systems necessitate the use of auxiliary capping agents[21-22], raising concerns about potential risks associated with these inorganic gating materials. Moreover, premature drug release before reaching the tumor site can lead to damage to healthy tissues[23]. Therefore, in the design of drug- carrying carriers, it is essential to consider the potential risks of gated materials and minimize drug release before reaching the tumor site.
Magnetic Fe3O4 nanomaterials have recently garnered considerable attention in the field of biomedical materials due to their superparamagnetism, excellent biocompatibility, and biodegradability[24-25]. Pullulan oxide (oxPL) stands out as an effective pH-responsive gatekeeper because it is an affordable and non-toxic material that can be easily manufactured, remains stable in neutral environments, and readily degrades in acidic conditions[26-27]. Hence, we propose coating Fe3O4 nanomaterials with MSNs containing disulfide bonds to serve as a drug carrier, aiming to achieve biodegradability and targeting capabilities. Additionally, oxPL can function as a gatekeeper to enable controlled drug release.
In this work, a novel pH/GSH dual-responsive mesoporous magnetic nanodrug carrier (NH2-SMNPs) was successfully synthesized. This prepared carrier had a good drug loading capacity, excellent stability, good biocompatibility, biodegradability, and the ability to reduce the side effects of premature drug release, As shown in Scheme 1, we first prepared mesoporous silica-coated Fe3O4 nanomaterials containing disulfide bonds (SMNPs). These SMNPs were then functionalized with amino groups (NH2-SMNPs). We selected doxorubicin (DOX) as a model drug and oxPL as a gatekeeper through the formation of a Schiff base bond to demonstrate the functionality of our carrier. The loaded DOX could be selectively released in weakly acidic tumor tissues via hydrolysis of the Schiff bonds. At the same time, oSMNPs/DOX exhibited sensitivity to the reducing agent GSH, which caused the disulfide bonds to break and allowed drug release under high GSH concentrations. Furthermore, loading and release tests, in vitro antitumor effects, and biosafety were studied. These findings suggest that oSMNPs/DOX is a promising pH/GSH dual-responsive drug for tumor therapy.
NaSaI=sodium salicylate, BTESPTs=bis[3-(triethoxysilyl)propyl] tetrasulfide, TEOs=tetraethyl silicate, APTEs=(3-aminopropyl)triethoxysilane, CTAB=cetyl trimethyl ammonium bromide.
Ferric chloride hexahydrate (FeCl3·6H2O), NaSaI, BTESPTs, anhydrous sodium acetate (NaOAc), trisodium citrate, TEOs, APTEs, pullulan and doxorubicin hydrochloride (DOX·HCl), and CTAB were purchased from Shanghai Aladdin Reagent Co., Ltd. Calcein acetoxymethyl ester (calcein-AM), 4′, 6-diamidino-2-phenylindole (DAPI), propidium iodide (PI), and Cell Counting Kit-8 (CCK-8) were obtained from Boster Biological Technology Co., Ltd. Other chemicals were purchased from Tianjin Damao Chemical Reagent Co., Ltd.
Transmission electron microscopy (TEM) images were captured using a JEM-2100 transmission electron microscope (accelerating voltage: 200 kV, working current: 110 μA, point resolution: 0.19 nm, lattice resolution: 0.1 nm, tilt angle: ±25°) (Tokyo, Japan). Ultraviolet-visible (UV-Vis) spectra measurements were performed using a UH5300 UV-Vis spectrophotometer (Tokyo, Japan). Fourier transform infrared (FTIR) spectroscopy was measured on a BRUKER FTIR spectrometer (Bruker, Germany). Powder X-ray diffraction (PXRD) patterns were obtained using a diffractometer (PANALY) with Cu Kα radiation (λ=0.154 05 nm) and the powder samples were scanned in the 2θ angle of 10° to 80° (working voltage: 25 kV, working current: 40 mA). The magnetic properties were measured using a SQUID vibrating sample magnetometer (VSM) (Quantum Design). The magnetization curves were recorded at 300 K with a magnetic field cycled between -20 000 and 20 000 G. Fluorescence images were captured using a Nikon Eclipse Ti2 inverted fluorescence microscope (Tokyo, Japan).
Briefly, 0.541 4 g of FeCl3·6H2O and 0.241 1 g of trisodium citrate were dissolved in 20 mL of ethylene glycol (EG) and stirred for 1 h. Subsequently, 1.217 0 g of NaOAc was added and the temperature was gradually increased to 80 ℃. After 30 min, the dispersed liquid was transferred into a Teflon container and placed in a stainless-steel autoclave reactor to heat at 200 ℃ for 10 h. The hydrothermal product was then centrifuged (15 000 r·min-1 for 30 min), washed three times with deionized (DI) water and ethanol, and freeze-dried under vacuum overnight to obtain the magnetic nanoparticles (MNPs).
0.090 g of MNPs and 0.210 mL of triethanolamine (TEA) were separately dissolved in 9 mL of H2O using ultrasound. Meanwhile, 0.150 g of CTAB and 0.105 g of NaSaI were dispersed into 45 mL of H2O at 80 ℃ to form a transparent solution. The two solutions were then mixed and vigorously stirred at 80 ℃ for 1 h to form an emulsion. Subsequently, a mixture of 1.5 mL of TEOs and 1.05 mL of BTESPTs was added dropwise and continuously stirred for 8 h. The resulting product was collected by centrifugation and washed three times with water and ethanol. The template was then removed using a hot EtOH-HCl solution. Finally, SMNPs were obtained by vacuum drying at 40 ℃.
A total of 120 mg of SMNPs were dissolved in 20 mL of toluene. The mixture was agitated at a temperature of 30 ℃ for 1 h. Afterward, 200 μL of APTEs was gradually added dropwise into the solution. The resulting combination was then refluxed for a period of 24 h to functionalize the carrier of SMNPs with amino groups. Subsequently, the product (NH2-SMNPs) was collected.
5 mg of DOX was weighed in a beaker, and 50 mL of phosphate-buffered saline (PBS, pH=7.4) was added to configure a stock solution of adriamycin at a mass concentration of 0.1 mg·mL-1. After that, the DOX stock solution was diluted into different mass concentrations (5, 10, 20, 25, 30, 35, 40, 45, 50, and 55 μg·mL-1). The absorbance at 480 nm was measured using a UV-Vis spectrophotometer.
Firstly, we conducted a drug-loading kinetics experiment to determine the drug-loading capacity of NH2-SMNPs. In brief, 1 mg of NH2-SMNPs was dispersed in 2 mL of PBS after ultrasound treatment. Following the addition of 2 mL of the DOX solution with a mass concentration of 0.01 mg·mL-1, the mixture was shaken at a specific time point. The resulting nanoparticles were magnetically separated at a predetermined time, and the concentration of DOX in the supernatant was determined using the spectrophotometric standard curve method. The adsorption capacity (qt) at a given time t was calculated using Eq.1:
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where ρ0 and ρt are DOX mass concentrations (mg·mL-1) at the initial time and time t, respectively, V (mL) is the volume of the solution and m (mg) is the mass of the carrier.
Subsequently, we conducted an isothermal adsorption experiment to investigate the drug-loading behavior. In short, eight portions of 1 mg of NH2-SMNPs were weighed and added to 4 mL of the DOX solution with mass concentrations of 0.125, 0.150, 0.175, 0.200, 0.225, 0.250, 0.275, and 0.300 mg·mL-1, respectively. The mixture was then subjected to ultrasonication for 20 min and shaking for 10 h in a light-proof shaker. After centrifuging (15 000 r·min-1 for 30 min), the absorbance at 480 nm was measured after appropriate dilution of the supernatant. The drug loading (qe) was calculated using Eq.2:
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where ρe is DOX mass concentration (mg·mL-1) at equilibrium.
A total of 50 mg of NH2-SMNPs and 12 mg of DOX were dispersed separately into 40 mL and 12 mL of DI water using ultrasound. The two suspensions were then mixed and shaken at 200 r·min-1 for 24 h at 37 ℃ in the dark. The resulting product (oSMNPs/DOX) was collected by centrifuging (15 000 r·min-1 for 30 min), and the supernatant was measured using a UV-Vis spectrophotometer at 480 nm to calculate the drug encapsulation efficiency. The DOX-loaded NH2-SMNPs were dissolved in a solution of 3 mg·mL-1 oxPL (20 mL), stirred continuously at room temperature for 12 h, and washed with DI water. The sample was finally freeze-dried for 24 h and labeled as oSMNPs/DOX.
In the drug release experiment, 10 mg of oSMNPs/DOX were dispersed separately into 25 mL of the PBS solution and divided into the following four groups: (1) pH=7.4; (2) pH=5.5; (3) pH=7.4 and GSH=10 mmol·L-1; (4) pH=5.5 and GSH=10 mmol·L-1. Subsequently, the eight samples were shaken at 200 r·min-1 and 37 ℃ in the dark. At regular intervals, the supernatant was taken out after centrifugation, and the released DOX content was calculated by measuring the absorbance at 480 nm. The concentration was determined using the DOX standard curve, and the release amount was calculated.
The CCK-8 was used to evaluate the cell viability. Briefly, human hepatocellular carcinomas (HepG2) and human colon cancer cells (HCT116) were added to 96-well plates (5×104 cells per well) and incubated for 24 h at 37 ℃ to allow adherence. The adhered cells were co-incubated with NH2-SMNPs or oSMNPs/DOX at 1, 5, 10, 30, 50, 70, and 90 μg·mL-1 (DOX equiv. 0.03-0.28 μg·mL-1). The CCK-8 reagent was added and incubated for 4 h. Then, the absorbance was measured at 450 nm on an enzyme-linked immunoassay instrument.
The cells (HCT 116) were seeded in a 96-well plate at a cell density of 5×104 per well and incubated for 12 h. The media were then removed, and the experimental group was treated with the medium containing oSMNPs/DOX. In contrast, the control group was cultured with the medium without any material. After another 12 h of culture, DAPI staining was conducted. First, the medium was aspirated from the 96-well plates, and the cells were washed three times with PBS. Then, the cells were fixed with 4% paraformaldehyde (PFA) for 2 h and washed three more times with PBS. Next, the cells were treated with TritonX-100 for 20 min and washed three more times with PBS. Subsequently, the cells were stained with 1% DAPI for 20 min and washed three times with PBS. Finally, cell imaging was performed using a fluorescence inversion microscope.
Fig. 1a and 1b present the TEM images of NH2-SMNPs and oSMNPs/DOX, as well as the particle size distributions of NH2-SMNPs. The TEM images reveal that the NH2-SMNPs had a uniform spherical shape with visible dendritic pores, indicating good dispersion. The disulfide bond-doped silicon dioxide layer on the nanoparticles had a thickness of approximately 20 nm (Fig. 1a). After successful drug loading, the pore structures became less distinct (Fig. 1b), confirming the successful loading of the drug DOX onto the nanomaterials. The NH2-SMNPs sample displayed uniform spherical particles with a size of 230 nm and a polymer dispersity index (PDI) of 0.146 (Fig. 1c), indicating good dispersion. As shown in the FTIR spectra in Fig. 1d, 590 cm-1 is the stretching vibration peak of the Fe—O bond, which is the characteristic absorption peak of Fe3O4. After the functionalization of nanoparticles, the corresponding peaks were also observed in infrared spectra. Among them, the strong peak at 690 cm-1 belonged to the stretching vibration of the C—S bond. The Si—O—Si stretching vibration peak was at 1 057 cm-1, which indicates that SiO2 containing —S—S— successfully coated Fe3O4[28-29]. Also, the broad absorption peak at 3 432 cm-1 corresponds to the stretching vibration peak of O—H or N—H, and the stretching vibration peak of C—H is at 2 927 cm-1. This indicates that amino groups were successfully introduced into the surface of the material. In addition, the attenuation of the —CHO peak at 1 720 cm-1 and the new stretching vibration peak at 1 656 cm-1 indicate that oxPL encapsulation was successful. Furthermore, the N2 adsorption-desorption isotherm of NH2-SMNPs demonstrated a type-Ⅳ isotherm, showing a homogeneous and narrow mesoporous size distribution. The surface area was measured to be 536 m2·g-1, with an average mesopore diameter of 2.42 nm (Fig. 1e). Fig. 1f shows PXRD patterns of MNPs, NH2-SMNPs, and oSMNPs/DOX samples. All samples showed sharp diffraction peaks at 2θ=30.6°, 35.99°, 43.71°, 57.71°, and 63.28°, which are assigned to the (220), (311), (400), (511), and (440) crystal planes, respectively, of Fe3O4 according to the standard card PDF No.85-1436. A prominent peak at 23° was also observed in the PXRD patterns of both samples, which is attributed to the SiO2 shell coated on the Fe3O4 nanoparticles. As shown in Fig. 1g, the Raman spectrum of CHO-SMNP carriers exhibited a stretching vibration peak at 623 cm-1, which confirms the presence of S—S bonds[18]. Additionally, the energy-dispersive X-ray spectroscopy (EDS) spectrum (Fig. 1g) reveals the presence of C, O, N, Si, S, and Fe elements in the NH2-SMNPs. The EDS data also suggests approximately 5.62% sulfur doping in the nanoparticles. Furthermore, Fig. 1i depicts the magnetization characterization of MNPs, NH2-SMNPs, and OSMNPs/DOX at room temperature. The saturation magnetizations (Ms) of MNPs, CHO-SMNPs, and NH2-SMNPs/DOX were approximately 61, 14, and 12 emu·g-1, respectively, which confirms potential use as a magnetically-targeted drug[30].
Fig. 2a shows the UV-Vis absorption spectra of DOX. It was evident from the figure that various DOX mass concentrations exhibited a maximum absorption peak at 480 nm. Therefore, the 480 nm UV wavelength was chosen to construct the standard curve and assess its drug loading. Fig. 2b displays the linear equation of the standard curve for DOX, A=0.018 82ρ+0.025 54 (R2=0.999 16), within a range of 5-55 μg·mL-1.
Fig. 3a presents the adsorption kinetics curve of DOX by NH2-SMNPs. The curve clearly shows that the loading of the DOX anticancer drug by the NH2-SMNP nanomaterial could be divided into three stages. Initially, during the first 50 min, DOX was rapidly loaded by the nanomaterial. Subsequently, the loading rate gradually slowed down between 50 and 150 min. Finally, the drug loading reached saturation after 3 h. In addition, Lagergren′s pseudo-first-order kinetic model (Eq.3) and Ho′s pseudo-second-order kinetic model (Eq.4) were used to further study the adsorption mechanism. Fig. 3b and 3c exhibit the linear relationship obtained using the pseudo-first-order and pseudo-second-order kinetic equations, respectively. These relationships portray the drug loading time (t) as the horizontal coordinate and ln(qe-qt) and t/qt as the vertical coordinates. The plots, in conjunction with Table 1, demonstrate that the loading process of DOX by the NH2-SMNP nanomaterial involves physical adsorption.
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| Lagergren′s pseudo-first-order kinetic model | Ho′s pseudo-second-order kinetic model | |||||
| qe / (mg·g-1) | k1 / min-1 | R2 | qe / (mg·g-1) | k2 / (g·mg-1·min-1) | R2 | |
| 53.33 | 0.030 69 | 0.999 48 | 72.62 | 0.001 02 | 0.998 94 | |
where qe (mg·g-1) is equilibrium adsorption capacity; qt (mg·g-1) is the drug loading at different time points; t (min) is the drug loading time; k1 and k2 are kinetic constants.
Then, the adsorption isotherm of NH2-SMNPs for DOX was investigated. As shown in Fig. 4a, with the increase in the DOX concentration, the DOX drug loading by NH2-SMNPs gradually increased. At a mass concentration of 300 mg·L-1, the maximum DOX loading capacity was 642 mg·g-1. We measured the drug-loading efficiency and encapsulation efficiency as 53.26% and 84.38% by UV-Vis, respectively. The single-layer Langmuir (Eq.5) and multi-layer Freundlich (Eq.6) isothermal adsorption models were employed, with ρe and ln ρe as the horizontal coordinates and ρe/qe and ln qe as the vertical coordinates, respectively, to analyze and discuss the drug loading of NH2-SMNPs (as depicted in Fig. 4b and 4c and summarized in Table 2). Fig. 4c provides a better reflection of the drug-loading mechanism of nanomaterials compared to Fig. 4b. Moreover, the correlation coefficient R2 (0.990 76) for the Freundlich model was higher than that for Langmuir model (0.247 91). This indicates that the drug-loading process of NH2-SMNPs for DOX aligns more closely with the Freundlich adsorption model. Therefore, it can be inferred that the primary driving force for drug loading was multi-molecular layer adsorption.
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| Langmuir isotherm model | Freundlich isotherm model | |||||
| qm / (mg·g-1) | KL / (L·mg-1) | R2 | n | KF / (mg1-1/n·L1/n·g-1) | R2 | |
| 5.884×103 | 7.418×10-5 | 0.247 91 | 1.089 | 3.258 5 | 0.990 76 | |
Langmuir model:
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Freundlich model:
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where qm (mg·g-1) is the drug loading in the saturated state; qe (mg·g-1) is the drug loading at equilibrium; KL (L·mg-1) is the dissociation constant; KF (mg1-1/n·L1/n·g-1) is the Freundlich constant; 1/n is the Freundlich component factor.
Given that the tumor cell microenvironment differs from normal cells[24], the release behaviors of DOX from NH2-SMNPs were investigated in different pH values and GSH concentrations. The results presented in Fig. 5 depict the kinetic release profiles of DOX from the oSMNPs/DOX when exposed to GSH concentrations of 0, 5, and 10 mmol·L-1 in 0.1 mol·L-1 PBS at different pH values (5.5, 6.8, and 7.4). It can be seen that the drug-release rate increased with the decrease in pH and the increase in the GHS concentration. Notably, at pH 5.5 with GSH of 10 mmol·L-1, DOX release reached a cumulative percentage of 81.53% after 6 h. Conversely, under the same conditions, DOX release was only 13.31% at pH 7.4 with a GSH of 0 mmol·L-1. These findings suggest that the oSMNPs/DOX nanoparticles exhibit a release behavior sensitive to both pH and GSH. The controlled-release properties of oSMNPs/DOX offer significant advantages for tumor treatment by prolonging the duration of drug release and maintaining sustained drug concentrations within tumor cells. This leads to enhanced therapeutic efficacy while minimizing side effects. Compared with the reported nanocarriers[31], this drug delivery system demonstrates superior performance in both drug loading and release.
We adopted the CCK-8 assay to evaluate the toxic effects of oSMNPs and oSMNPs/DOX (1-90 μg·mL-1) on human umbilical vein endothelial cells (HUVEC), HepG2, and HCT116 (Fig. 6) to demonstrate that the materials were advantageous. Fig. 6a illustrates that neither oSMNPs nor oSMNPs/DOX demonstrated significant cytotoxicity toward HUVEC cells. Cell survival rates exceeded 92% after 24 h of co-incubation with various concentrations of both materials. It was seen that the cell survival rates of the oSMNPs were around 96%, indicating the high biocompatibility and low cytotoxicity of oSMNPs, as shown in Fig. 6b. However, as shown in Fig. 6c, the cytotoxicity to both types of cancer cells increased with the concentration of oSMNPs/DOX and displayed concentration-dependent behavior. At a mass concentration of 50 μg·mL-1, approximately 70.33% of HepG2 cells and 60.42% of HCT 116 cells died after 24 h. These findings indicate that oSMNPs meet the requirements for drug delivery systems and show potential for various applications.
Further experiments using live-dead staining were conducted to validate the killing effect of oSMNPs/DOX on cancer cells. According to Fig. 7, PBS and oSMNPs had minimal cytotoxicity against HepG2. When HepG2 cancer cells were co-cultured with oSMNPs/DOX (ρDOX=0.5 μg·mL-1) for 4 h, subsequent staining with calcein-AM and PI revealed a significant number of dead cancer cells under a fluorescence inverted microscope. This demonstrates that oSMNPs/DOX possessed a cytotoxic effect on cancer cells.
Scale bar: 100 μm.
It is essential to target DOX release into the nucleus to optimize its therapeutic effectiveness. A fluorescent inverted microscope was employed to observe the uptake of oSMNPs/DOX. As depicted in Fig. 8, the control group of untreated HCT116 cells exhibited normal morphology with intense blue fluorescence in the blue channel post-DAPI staining while displaying no fluorescence signal in the red channel. On the other hand, the experimental group of HCT116 cells treated with oSMNPs/DOX displayed blue fluorescence in the blue channel and red fluorescence in the red channel after DAPI staining. The red fluorescence results from the excitation of DOX, suggesting the successful uptake of the drug DOX via NH2-SMNP nanocarriers by the HCT116 cells. These findings highlight the ability of oSMNPs/DOX to be internalized by cancer cells, a critical factor for facilitating effective drug delivery into cancer cells.
Scale bar: 100 μm.
In conclusion, a novel mesoporous magnetic nanodrug carrier containing disulfide bonds (NH2-SMNPs) was successfully synthesized. The resulting oSMNPs/DOX offers several advantages: high DOX loading efficiency for chemotherapy, pH/GSH dual-responsive drug release, uniform sulfur doping, gated oxPL to reduce burst release, exceptional biocompatibility, and stability. The oSMNPs/DOX nanodrugs exhibited significant in vitro antitumor effects in trials using HepG2 and HCT 116. Therefore, our findings position these nanomaterials as promising platforms for drug delivery, integrating dual-responsive drug-controlled release mechanisms with passive tumor-specific targeting. Future research will focus on conducting more extensive in vivo evaluations to validate these outcomes.
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Scheme 1 Schematic diagram of the synthesis of the pH/GSH dual-responsive drug carrier and drug release
NaSaI=sodium salicylate, BTESPTs=bis[3-(triethoxysilyl)propyl] tetrasulfide, TEOs=tetraethyl silicate, APTEs=(3-aminopropyl)triethoxysilane, CTAB=cetyl trimethyl ammonium bromide.
Figure 1 TEM images of (a) NH2-SMNPs and (b) oSMNPs/DOX; (c) Size distribution of oSMNPs/DOX; (d) FTIR spectra of MNPs, NH2-SMNPs, oSMNPs/DOX, and oxPL; (e) Nitrogen adsorption-desorption isotherm of NH2-SMNPs (Inset: the pore size distribution); (f) PXRD patterns of MNPs, NH2-SMNPs, and oSMNPs/DOX; (g) Raman spectrum of NH2-SMNPs; (h) EDS spectrum of NH2-SMNPs; (i) Magnetization curves of MNPs, NH2-SMNPs, and oSMNPs/DOX
Figure 2 (a) UV-Vis absorption spectra of DOX; (b) Plot of the standard curve for DOX solutions with different concentrations
Figure 3 (a) Adsorption kinetics curve of DOX on CHO-SMNPs; Linear fittings of the dynamic model for (b) Lagergren′s pseudo-first-order and (c) Ho′s pseudo-second-order models
Figure 4 (a) Adsorption isotherm of DOX on NH2-SMNPs; Linear fitting plots for (b) Langmuir adsorption isotherm model and (c) Freundlich adsorption isotherm model
Figure 5 Release profiles of oSMNPs/DOX in PBS with different pH values and GSH concentrations
Figure 6 Cell viabilities of HUVEC incubated with oSMNPs or oSMNPs/DOX; Cell viabilities of HepG2 and HCT 116 incubated with (b) oSMNPs or (c) oSMNPs/DOX
Figure 7 Fluorescence images of calcein-AM and PI co-labeled HepG2 cells after varied treatments
Scale bar: 100 μm.
Figure 8 Fluorescent inverted microscope images of HCT116 cells treated with oSMNPs/DOX
Scale bar: 100 μm.
Table 1. Pharmacokinetic parameters of DOX on NH2-SMNPs
| Lagergren′s pseudo-first-order kinetic model | Ho′s pseudo-second-order kinetic model | |||||
| qe / (mg·g-1) | k1 / min-1 | R2 | qe / (mg·g-1) | k2 / (g·mg-1·min-1) | R2 | |
| 53.33 | 0.030 69 | 0.999 48 | 72.62 | 0.001 02 | 0.998 94 | |
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Table 2. Related parameters of Langmuir and Freundlich isotherm adsorption models of DOX by NH2-SMNPs
| Langmuir isotherm model | Freundlich isotherm model | |||||
| qm / (mg·g-1) | KL / (L·mg-1) | R2 | n | KF / (mg1-1/n·L1/n·g-1) | R2 | |
| 5.884×103 | 7.418×10-5 | 0.247 91 | 1.089 | 3.258 5 | 0.990 76 | |
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