Development of liposome capped mesoporous silica nanoparticle for anticancer drug delivery

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Mesoporous silica nanoparticles (MSNs) have been used as an anticancer drug delivery system with high safety and entrapment capacity thanks to their large internal space for drug accommodation, durable structure, and good biocompatibility. However, the treatment efficiency of the bare MSNs is limited due to its drug leakage and burst release. In this study, a phospholipid bilayer was covered on the MSNs surface (MSN@Lip) as a liposomal cap that not only reduced drug leakage but also improved the stability of the colloidal system.

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Nội dung Text: Development of liposome capped mesoporous silica nanoparticle for anticancer drug delivery

Cite this paper: Vietnam J. Chem., 2023, 61(S3), 51-58 Research Article DOI: 10.1002/vjch.202300052 Development of liposome capped mesoporous silica nanoparticle for anticancer drug delivery Dinh Tien Dung Nguyen1,2, Ngoc Hoi Nguyen1,3, Ngoc-Hang Truong-Thi2, Yern Chee Ching4, Tan Phu Nguyen2, Dai Hai Nguyen3* 1 Graduate University of Science and Technology, Vietnam Academy of Science and Technology, Hanoi 10000, Viet Nam 2 Institute of Applied Materials Science, Vietnam Academy of Science and Technology, 01B TL29 District 12, Ho Chi Minh City 70000, Viet Nam 3 Institute of Chemical Technology, Vietnam Academy of Science and Technology, 01A TL29 District 12, Ho Chi Minh City 70000, Viet Nam 4 Department of Chemical Engineering, Faculty of Engineering, University of Malaya, Kuala Lumpur 50603, Malaysia Submitted February 18, 2023; Revised June 7, 2023; Accepted June 23, 2023 Abstract Mesoporous silica nanoparticles (MSNs) have been used as an anticancer drug delivery system with high safety and entrapment capacity thanks to their large internal space for drug accommodation, durable structure, and good biocompatibility. However, the treatment efficiency of the bare MSNs is limited due to its drug leakage and burst release. In this study, a phospholipid bilayer was covered on the MSNs surface (MSN@Lip) as a liposomal cap that not only reduced drug leakage but also improved the stability of the colloidal system. The chemical structure of MSNs and MSN@Lip was characterized by Fourier transform infrared spectroscopy (FT-IR) and energy-dispersive X-ray spectroscopy (EDX). The particle size and morphology were determined by dynamic light scattering (DLS). The results demonstrated that the MSN@Lip was successfully synthesized with the hydrodynamic diameter and zeta potential of 177.13±1.5 nm and -57.57±4.00 mV, respectively. The optimal condition was sonication for 30 minutes at 60°C, with the Lip-MSNs ratio as 3:1 (w/w). The SEM images showed that MSN@Lip has a spherical shape with high monodispersity. Releasing profile of doxorubicin (DOX) indicated that the formation of liposomal cap on MSN successfully reduced DOX burst release. The MSN@Lip is a potential delivery material for clinical translation because of colloidal stability, good drug loading content, and sustainable drug release. Keywords. Mesoporous silica nanoparticle, liposome, bilayer coating, doxorubicin, drug delivery. 1. INTRODUCTION protect drugs against enzymatic degradation, and bring it to the targets. However, drugs are Mesoporous silica nanoparticles (MSNs) have been encapsulated in the MSNs just by simply physical considered one of the most promising nanocarriers adsorption on the surface or into the mesopores, thanks to mesopores embedded inside the silica consequently can be desorbed easily and leading to a framework providing the MSNs large inner space burst release. Thus, released drugs would be uptaken with high internal surface area for cargoes by healthy cells, tissues, and organs before reaching accommodation and adsorption.[1,2] In addition, the the targets (tumors, organs, etc.), which not only chemical structure of MSNs contains Si-O-Si reduces the treatment efficiency, but also causes linkages and silanol groups (Si-OH or Si-Oˉ), making many severe side-effects due to high cytotoxicity of MSNs stable to external stimuli such as mechanical drugs [5]. Therefore, capping the mesopores of MSNs and thermal stress, and physicochemistry of for controlled drug release is necessary. In previous microenvironment.[3] Furthermore, because of highly studies, MSNs was conjugated with various capping biocompatible and biodegradable properties, the agents such as inorganic nanoparticles (Au, CdS, MSNs are considered one of the safest materials for Fe3O4), macrocyclic organic molecules drug delivery applications.[4] Besides, the MSNs can (cyclodextrin), polymers (proteins, polysaccharides, 51 Wiley Online Library © 2023 Vietnam Academy of Science and Technology, Hanoi & Wiley-VCH GmbH
25728288, 2023, S3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/vjch.202300052 by Readcube (Labtiva Inc.), Wiley Online Library on [01/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Vietnam Journal of Chemistry Dai Hai Nguyen et al. polyethylene-glycol, polyethylenimine).[6,7] made from non-toxic phospholipids and Recently, many researches have coated cholesterol.[14] inorganic nanoparticles such as magnetic, silica, and In this research, we aimed to synthesize a stable gold nanoparticles with lipid bilayers to enhance the and highly monodispersed MSNs surface coated with nanoparticles biocompatibility and stability in lipid bilayer (MSN@Lip) for burst drug release aqueous solutions for biomedical applications.[8-10] limitation. To specify, the MSN was firstly The lipid bilayers with the same structure as cell synthesized via Stöber method, then surface membrane covering the particles surface not only modification with APTES to yield MSN-NH2. The reduces the aggregation and cytotoxicity, but also MSN@Lip was synthesized by mixing and sonicating affects the cellular uptake and cytolocalization of the the MSN-NH2 with liposome solution in various particles.[11,12] One of the most efficient strategies for conditions and liposome to MSNs ratios. The coating a lipid bilayer on inorganic nanoparticles is characterization of MSN@Lip was determined by utilizing liposome.[13] Liposomes are highly evaluated FTIR, DLS, SEM, and EDX. Finally, the drug as safe biomaterials with high biocompatibility, encapsulation and releasing behavior of DOX loaded biodegradability, and no immunogenicity for MSN@Lip (DOX@MSN@Lip) was evaluated to systemic and non-systemic administrations thanks to demonstrate the prolong drug release efficiency of the the colloidal vesicular structures with the bilayer liposome cap on the MSNs surface. Liposome TEOS APTES DOX CTAB NH3 Ethanol MSNs MSN-NH2 DOX@MSN-NH2 -NH2 DOX Liposome adsorption DOX@MSN@Lip Bilayer formation and deformation Figure 1: Scheme of MSN@Lip (DOX@MSN@Lip) synthesis 2. MATERIALS AND METHODS Japan. All chemicals were reagent grade and used without further purification. 2.1. Materials 2.2. Preparation of MSNs Tetraethyl orthosilicate (TEOS, 98%), 3-amino- propyltriethoxysilane (APTES, 99%), and cholesterol The synthesis of MSNs was based on the Stöber (≥ 92.5%) were purchased from Sigma-Aldrich (St method.[15] Briefly, template preparation was Louis, MO, USA). Ammonia solution (NH3 (aq), conducted by stirring the mixture containing CTAB 28%) and ethanol (≥ 99.9%) were bought from (2.6 g, 7.1 mmol) and deionized water (64 ml) at 60 Scharlau (Spanish). Cetyltrimethylammonium °C for 30 min. Ethanol solution (11.25 ml, 0.2 mol) bromide (CTAB, ≥ 99%, India) was supplied by and ammonia solution (2.8%) (550 ml, 0.9 mmol) Himedia. Soybean lecithin was supplied by TCI in were added and stirred for 10 min to create a catalyst © 2023 Vietnam Academy of Science and Technology, Hanoi & Wiley-VCH GmbH www.vjc.wiley-vch.de 52
25728288, 2023, S3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/vjch.202300052 by Readcube (Labtiva Inc.), Wiley Online Library on [01/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Vietnam Journal of Chemistry Development of liposome capped mesoporous… environment. TEOS (8 ml, 35.8 mmol) was added by FT-IR/NIR Spectroscopy Frontier instrument with dropwise to the surfactant solution. The mixture was KBr as a background, and EDX spectroscopy. The continuously stirred at 60°C for 2h for the hydrolysis particles size and zeta potential were investigated by and condensation process. The final solution was DLS method using NanoParticle Size SZ 100 dialyzed in water for 24 hours using a cellulose instrument. The morphology of particles was membrane (MWCO 3.5 kDa, Spectrum Laboratories, determined by SEM (S4800 Scanning Electron Inc., USA), then dialyzed in acetic acid and alcohol Microscope instrument). for 3 days before being dialyzed in distilled water for 3 days to remove CTAB excess and purify the 2.7. Preparation of DOX loaded MSN@Lip product. Finally, the final product was obtained after lyophilization. DOX was dissolved in deion water (1 mg/mL) and mixed with MSN-NH2 colloid for 24 hours, then the 2.3. Preparation of MSN-NH2 mixture was added to liposome solution followed by sonication at 60 °C for 30 minutes. The solution was The synthesis of MSN-NH2 was based on the post centrifuged at 10000 rpm for 30 minutes to separate grafting method.[16] The detailed procedure was the particles and the supernatant, which was illustrated in figure 7. Briefly, MSNs (100 mg) were measured by UV-Vis spectroscopy at 480 nm to dispersed into ethanol (20ml) with a stirring bar for quantify the unloaded DOX. The entrapment 30 min at room temperature. The prepared solution of efficiency (EE) and loading content (LC) was APTES and ethanol (4:1, v/v) was then introduced calculated by equation (1) and (2), respectively. The dropwise into the mixture under intensive stirring, DOX loaded MSN@Lip (DOX@MSN@Lip) was and the reaction was maintained at room temperature then lyophilized to yield dry powder. for 24h. The solution was purified and washed with ethanol and distilled water three times by 2.8. In vitro drug release experiments centrifugation at 10000 rpm for 10 min at 25°C. The final product was obtained after lyophilization. To investigate the in vitro drug release, DOX@MSN@Lip was dispersed in 5 mL PBS 2.4. Preparation of liposome solution with pH 7.4 and transferred into a dialysis tube with MWCO = 3.5 kDa. The tube was then The preparation of liposomes was conducted by the soaked in 20 mL PBS pH 7.4, stirred at 50 rpm, 37 lipid film hydration method.[17] In the first step, the °C. At time intervals as 1, 3, 6, 12, 24, and 36 hours, mixture containing soybean lecithin, cholesterol, and 2 mL of releasing solution was collected and replaced CTAB (90:10:1, w/w) was dissolved in chloroform by an equivalent volume of fresh medium. The (10ml) and then evaporated to form a thin lipid film concentration of released DOX was determined by by using a rotary evaporator. The lipid film was UV-Vis spectroscopy. hydrated with deionized water (10 ml) at 60°C for 1h. Next, the homogenous liposomes were sonicated at 3. RESULTS AND DISCUSSION 60°C for 30 min. The prepared liposomes were stored at 4°C. 3.1. Preparation of MSNs, MSN-NH2 and liposome 2.5. Preparation of MSN@Lip The MSNs were synthesized via Stöber method using TEOS as a silica source, CTAB as a cationic The MSN-NH2 was coated with liposome by bilayer surfactant, and ethanol and ammonia solution as formation method with ultrasonic assistance.[18,19] alkaline conditions. The negatively charged silica The MSN-NH2 has been dispersed in deionized water source instantaneously interacted with the positively with concentration of 1 mg/mL before it was mixed charged micelles under alkaline conditions. After the with liposome solution at 60°C for 30 minutes. The sol-gel process, network silica with template of mixture was sonicated in ultrasonic bath at 60 °C for surfactant was removed by the dialysis method. 30 minutes to form homogenous solution and reduce MSNs showed the porous honeycomb structure of multidispersity of particles. Some parameters of the silica. The final product was obtained as a white fine process were investigated such as temperature and powder after lyophilization. The DLS results showed time of sonicating step, and liposome to MSNs ratios. in figure 2 indicated that the hydrodynamic diameter 2.6. Characterization of MSNs was 167.18±1.35 nm with high monodispersity when the polydispersity index (PDI) Chemical structure of the materials was characterized was 0.144±0.070. The zeta potential of MSNs was © 2023 Vietnam Academy of Science and Technology, Hanoi & Wiley-VCH GmbH www.vjc.wiley-vch.de 53
25728288, 2023, S3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/vjch.202300052 by Readcube (Labtiva Inc.), Wiley Online Library on [01/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Vietnam Journal of Chemistry Dai Hai Nguyen et al. -27.73±1.63 mV, which shows that particles in 2 indicated that the liposome was high monodispersed aqueous media tend to repel each other. Negatively nanoparticle with hydrodynamic diameter of charged MSNs indicated that the silanol groups 154.85±1.389 nm, and the PDI of 0.245±0.033. The (Si-OH) were deprotonated to form Si-O-Si on the zeta potential of liposome was -63.23±1.169 mV, surface of MSNs. indicating the stability of liposome in physiological conditions. A) 20 3.2. Preparation of MSN@Lip 3.2.1. Investigation of sonication time and Frequency (%) 15 temperature 10 The formation of MSN@Lip in different sonication time and temperature were shown in table 1. The 5 phospholipid bilayer of liposomes could transition from the highly ordered gel phase to the fluid liquid 0 crystal phase when the temperature increases around 10 100 1000 the phase transition temperature, which is 50 to 60°C Diameter (nm) for soybean lecithin.[20] The MSN@Lip prepared at B) 5 30°C would be separated into heterogeneous phases including liposomes and MSN-NH2 because the MSN phospholipids are closely packed and form a rigid gel Intensity (a.u.) 4 MSN-NH2 phase, thus the liposomes would be difficult to 3 Liposome deform in structure to coat the surface of silica. When the temperature approaches the phase transition 2 temperature (at 60°C), the phospholipid membrane transits from a highly ordered gel phase to a fluid 1 liquid crystal phase, leading to the shape deformation of liposomes, which makes them self-assemble on the 0 surface of MSN-NH2 via electrostatic interaction. The -100 -50 0 50 100 hydrodynamic diameter of MSN@Lip was Zeta potential (mV) 208.77±2.34 nm and 204.1±12.57 nm when sonicated Figure 2: DLS particle size (A) and zeta potential in 30 and 60 minutes, respectively. Therefore, (B) of MSNs, MSN-NH2, and liposome increasing the sonication time did not change the size distribution of MSN@Lip, but reduces the stability of The MSN-NH2 particles were synthesized the system, demonstrated by the increase of PDI from through the post grafting method by reacting MSNs 0.373 to 0.465. In contrast, when the temperature with APTES under conditions containing ethanol. approaches 90°C, the associative interactions The silane termination observed in APTES allows its between phospholipid molecules are reduced, leading interaction with the hydroxyl group of MSNs through to membrane fluidization. Their phospholipid tails hydrolysis and condensation reactions, which enables become random, thereby lowering membrane aminopropyl groups to bind to the surface of MSNs stiffness and causing damage to pores and disk by a covalent bond. The obtained product was a fine bilayers. Hence, the yellow precipitation of white powder after lyophilization. The results of the MSN@Lip appeared after sonication time for both 30 size distribution and zeta potential of MSN-NH2 are and 60 minutes, and the hydrodynamic diameter of shown in figure 2. The particle size of MSNs MSN@Lip would not be determined by DLS. increased slightly from 167.18±1.35 nm to Therefore, the sonication time and temperature 175.57±4.59 nm since polymer strands of APTES should be selected at 60°C for 30 minutes. were coated on the surface of MSNs. The zeta potential of MSNs has shifted from -27.73±1.63 mV 3.2.2. Investigation of MSNs to liposome ratios to +14.23±2.94 mV due to the attachment of amine molecules. The MSN@Lip was prepared at various ratios Liposomes were synthesized by the lipid film between liposome and MSNs, including 0:1 (MSNs), hydration method with assistance of ultrasound to 1:1, 3:1, 5:1, 10:1, and 1:0 (liposome). The average generate homogenous liposomes. The results in figure particles size and zeta potential of MSN@Lip in © 2023 Vietnam Academy of Science and Technology, Hanoi & Wiley-VCH GmbH www.vjc.wiley-vch.de 54
25728288, 2023, S3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/vjch.202300052 by Readcube (Labtiva Inc.), Wiley Online Library on [01/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Vietnam Journal of Chemistry Development of liposome capped mesoporous… Table 1: Characterization of MSN@Lip synthesized in different sonication time and temperature. DLS results after sonication Temperature (°C) Observation 30 minutes 60 minutes Size (nm) PDI Size (nm) PDI 30 Separating layer - - - - 60 Well-dispersed 208.77±2.34 0.373±0.087 204.1±12.57 0.465±0.09 Forming yellow 90 - - - - precipitation various liposome to MSNs ratios were shown in The excess of liposomes could occur in the figure 3. Initially, the hydrodynamic diameter of medium, resulting in reducing the particle size of MSN-NH2 and liposomes were 172.45±3.098 and MSN@Lip compared to the particle size of MSN- 155.83±1.703 nm, respectively. When increasing the NH2. Therefore, the liposome excess needs to be Lip-MSNs ratios to 1:1, 3:1 and 5:1, the particle size removed from the solution by centrifugation to obtain of MSN@Lip was firstly rose to 208.77±2.34 nm the final product. However, centrifugation could (1:1), then decreased to 177.13±1.5 nm (3:1) and contribute to reducing the productivity synthesis of 163.96±1.8 nm (5:1). However, there was no MSN@Lip. Further, the investigation of rotation time significant difference in particle size when the Lip- during centrifugation was a notable issue to ensure MSNs ratios were increased to 7:1 and 10:1 (p < the lipid removed during centrifugation. As a 0.05). The zeta potential of MSN-NH2 also shifted consequence, the investigation of Lip-MSNs ratios from 15.96±5.34 mV to -43.33±0.351 mV after was established to select a ratio in which both the fusion with liposomes in 1:1 Lip-MSNs ratio. This concentration of liposomes and MSN-NH2 were indicated that the lipid bilayers could be coated on the sufficient to self-assemble each other. Therefore, the surface of positively charged MSN-NH2. Lip-MSNs of 3:1 should be selected since it adapts to the requirements bilayer on the surface of MSNs A) 250 could not be of the experiment for obtaining the final Day 1 Day 3 Day 7 product without purification. Particle size (nm) 200 3.2.3. Stability of MSN@Lip 150 The stability of MSN@Lip was investigated after 1 100 day, 3 days and 7 days by DLS. The results in Figure 3 shown that there was no change observed in the 50 hydrodynamic diameter of MSN-NH2 (0:1), while the hydrodynamic diameter of liposomes (1:0) has 0 shifted from 155.83±1.703 to 198.8±2.85 nm due to 0:1 1:1 3:1 5:1 7:1 10:1 1:0 agglomeration of vesicles. The particle size of Lip to MSN ratios MSN@Lip did not change significantly over 7 days B) 40 (p < 0.05), indicating that MSN-NH2 as rigid Day 1 Day 3 Day 7 nanoparticles can stabilize the liposomes. 20 Zeta potential (mV) 0 3.2.4. FTIR -20 The FTIR spectra of MSNs, MSN-NH2, liposomes -40 and MSN@Lip are shown in figure 4. The MSNs -60 spectra showed the specific signals at 468 cm-1, 1074 -80 cm-1, and 3441 cm-1 corresponding to Si-O- stretching vibration, asymmetric stretching vibration of Si-O-Si -100 bridges, and Si-OH, respectively (figure 4 (a)). The 0:1 1:1 3:1 5:1 7:1 10:1 1:0 MSN-NH2 spectra presented obvious bands at 1540 Lip to MSN ratios cm-1, and 2926 cm-1, which were assigned to the Figure 3: DLS particle size (A) and zeta potential primary amine (N-H) bending, and methylene of (B) of MSN@Lip at different MSNs to liposome organosilanes attached to the MSNs framework ratios after 1, 3 and 7 days (figure 4 (b)). The liposomes spectra presented bands © 2023 Vietnam Academy of Science and Technology, Hanoi & Wiley-VCH GmbH www.vjc.wiley-vch.de 55
25728288, 2023, S3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/vjch.202300052 by Readcube (Labtiva Inc.), Wiley Online Library on [01/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Vietnam Journal of Chemistry Dai Hai Nguyen et al. at 1232, 1469, 1742, and 2856-2929 cm-1, which were diameter of about 170 nm. The surface assigned to P=O, C-H (-CH2-), C=O, and C-H characterization of MSNs and MSN@Lip were (CH3-) stretching vibrations, respectively (figure 4 evaluated by the elemental analysis using the Energy (c)). The MSN@Lip spectra (figure 4 (d)) displayed Dispersive X-ray Spectroscopy on the SEM. The all characteristic bands of MSN-NH2 and liposomes, spectrum of MSNs shown the weight percentage of Si illustrating the hybridization of MSNs with and O as 42.32% and 57.68 %, respectively, liposomes. indicating the silanol groups and Si-O-Si bridges on the surface of MSNs (Figure 5B). The spectrum of a) MSN@Lip presented the components of the lipid bilayer membrane of liposomes around the surface with 57.68% carbon, 35.64% oxygen, and 0.38% 3441 phosphorus. Besides, the weight percentage of silica b) has reduced from 42.32% to 6.51%, indicating that Transmittance (%) the surface of MSNs was coated by liposomes (figure 2926 1540 5D). c) 3.3. Preparation of DOX@MSN@Lip d) 1232 The DOX loaded MSN@Lip was prepared via diffusion method followed by lipid bilayer formation for capping to keep DOX in MSNs pores. The EE and 468 LC were found to be 62.66% and 5.28%, respectively. 2929 1742 1469 1074 3.4. In vitro drug releasing 4000 3500 3000 2500 2000 1500 1000 500 Wavenumber (cm-1) ) Wavenumber (cm-1 The releasing profile of free DOX and Figure 4: FTIR spectra of (a) MSNs, (b) MSN-NH2, DOX@MSN@Lip were shown in Figure 6. The (c) liposome, and (d) MSN@Lip results indicated that the free DOX burst released with 69.84% after 5 hours, then rose slightly to 3.2.5. SEM and EDX 74.29% after 36 hours. In contrast, the DOX@MSN@Lip performed sustainable release of The morphology of MSNs and MSN@Lip were DOX with 9.64% after 6 hours, which rose gradually evaluated by SEM, and the results were shown in to 24.82% after 36 hours. These results demonstrated figure 5. Both MSNs and MSN@Lip presented the that the liposomal cap on MSNs surface efficiently spherical and monodispersed nanoparticle with diminished drug releasing of DOX from the carriers. Figure 5: SEM images of MSNs (A) and MSN@Lip (C). Elemental analysis of MSNs (B) and MSN@Lip (D) © 2023 Vietnam Academy of Science and Technology, Hanoi & Wiley-VCH GmbH www.vjc.wiley-vch.de 56
25728288, 2023, S3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/vjch.202300052 by Readcube (Labtiva Inc.), Wiley Online Library on [01/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Vietnam Journal of Chemistry Development of liposome capped mesoporous… 80 mesoporous silica nanoparticle based on the sol–gel process and applications in controlled release, Accounts of chemical research, 2007, 40(9), 846-853. Released DOX (%) 60 4. Jeelani P. G., Mulay P., Venkat R., Ramalingam C. Free DOX Multifaceted application of silica nanoparticles. A DOX@MSN@Lip review, Silicon, 2020, 12(6), 1337-1354. 40 5. Yang P., Gai S., Lin J. Functionalized mesoporous silica materials for controlled drug delivery, Chemical Society Reviews, 2012, 41(9), 3679-3698. 20 6. Nik A. B., Zare H., Razavi S., Mohammadi H., Ahmadi P. T., Yazdani N., Bayandori M., Rabiee N. 0 and Mobarakeh J. I. Smart drug delivery: Capping strategies for mesoporous silica nanoparticles, 0 10 20 30 40 Microporous and Mesoporous Materials, 2020, 299 Time (hour) 110115. Figure 6: DOX release profile of free dox and 7. Kuang Y., Zhai J., Xiao Q., Zhao S., Li C. dox@msn@Lip Polysaccharide/mesoporous silica nanoparticle-based drug delivery systems: A review, International 4. CONCLUSIONS Journal of Biological Macromolecules, 2021, 193 457-473. To conclude, the MSN@Lip was successfully 8. Traini G., Ruiz-de-Angulo A., Blanco‐Canosa J. B., synthesized from MSN-NH2 and liposome via lipid Zamacola Bascaran K., Molinaro A., Silipo A., self-assembly process with assistance of ultrasound. Escors D., Mareque‐Rivas J. C. Cancer Immunotherapy of TLR4 Agonist-Antigen Constructs Some parameters of the process such as sonication Enhanced with Pathogen-Mimicking Magnetite time and temperature, and liposome to MSNs ratios Nanoparticles and Checkpoint Blockade of PD-L1, were investigated. The optimal condition was Small, 2019, 15(4), 1803993. sonication for 30 minutes at 60°C, with the Lip- 9. Du B., Gu X., Han X., Ding G., Wang Y., Li D., Wang MSNs ratio as 3:1 (w/w). The chemical E., Wang J. Lipid-coated gold nanoparticles characterization of MSN@Lip was demonstrated by functionalized by folic acid as gene vectors for FT-IR and EDX spectroscopy. The hydrodynamic targeted gene delivery in vitro and in vivo, diameter and zeta potential of MSN@Lip was ChemMedChem, 2017, 12(21), 1768-1775. 177.13±1.5 nm and -57.57±4.00 mV, respectively. 10. Durfee P. N., Lin Y. S., Dunphy D. R., Muñiz A. E. J., The particle size results were confirmed by SEM Butler K. S., Humphrey K. R., Lokke A. J., Agola J. images. DOX was successfully loaded in MSN@Lip O., Chou S. S., Chen I.-M. Mesoporous silica with EE of 62.66% and LC of 5.28%. The releasing nanoparticle-supported lipid bilayers (protocells) for profile of DOX@MSN@Lip demonstrated that the active targeting and delivery to individual leukemia formation of liposomal cap on MSNs surface had cells, ACS nano, 2016, 10(9), 8325-8345. efficiently diminished the burst release of DOX. 11. Tada D. B., Suraniti E., Rossi L. M., Leite C. A., Oliveira C. S., Tumolo T. C., Calemczuk R., Livache Acknowledgements. This research is supported by T., Baptista M. S. Effect of lipid coating on the Institute of Chemical Technology, Vietnam Academy interaction between silica nanoparticles and of Science and Technology. membranes, Journal of Biomedical Nanotechnology, 2014, 10(3), 519-528. REFERENCES 12. Yang S., Song S., Han K., Wu X., Chen L., Hu Y., Wang J., Liu B. Characterization, in vitro evaluation 1. Mekaru H., Lu J., Tamanoi F. Development of and comparative study on the cellular internalization mesoporous silica-based nanoparticles with controlled of mesoporous silica nanoparticle-supported lipid release capability for cancer therapy, Advanced drug bilayers, Microporous and Mesoporous Materials, delivery reviews, 2015, 95, 40-49. 2019, 284, 212-224. 2. Zhang W., Liu M., Liu A., Zhai G. Advances in 13. Luchini A., Vitiello G. Understanding the nano-bio functionalized mesoporous silica nanoparticles for interfaces: Lipid-coatings for inorganic nanoparticles tumor targeted drug delivery and theranostics, Current as promising strategy for biomedical applications, Pharmaceutical Design, 2017, 23(23), 3367-3382. Frontiers in chemistry, 2019, 7, 343. 3. Trewyn B. G., Slowing I. I., Giri S., Chen H. T., Lin 14. Singh A. P., Biswas A., Shukla A., Maiti P. Targeted V. S. Y. Synthesis and functionalization of a therapy in chronic diseases using nanomaterial-based © 2023 Vietnam Academy of Science and Technology, Hanoi & Wiley-VCH GmbH www.vjc.wiley-vch.de 57
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