Article pubs.acs.org/journal/abseba
Trehalose-Conjugated, Photofunctionalized Mesoporous Silica Nanoparticles for Efficient Delivery of Isoniazid into Mycobacteria Juan Zhou,† Kalana W. Jayawardana,‡ Na Kong,† Yansong Ren,† Nanjing Hao,‡ Mingdi Yan,*,‡,† and Olof Ramström*,† †
Department of Chemistry, KTH−Royal Institute of Technology, Teknikringen 30, S-10044 Stockholm, Sweden Department of Chemistry, University of Massachusetts Lowell, 1 University Avenue, Lowell, Massachusetts 01854, United States
‡
S Supporting Information *
ABSTRACT: Glyconanoparticle carriers have been synthesized and efficiently delivered into mycobacteria. Mesoporous silica nanoparticles were functionalized with α,α-trehalose through azide-mediated surface photoligation, and loaded with the antitubercular drug isoniazid. The glyconanoparticles showed high isoniazid loading capacity and higher antimicrobial activity than the free drug.
KEYWORDS: mesoporous silica nanoparticle, drug delivery, isoniazid, trehalose
1. INTRODUCTION Tuberculosis (TB), a chronic indfectious disease primarily caused by Mycobacterium tuberculosis, is a major global health threat that affects millions of people every year.1,2 The advent of AIDS, drug-resistant strains of M. tuberculosis, drug abuse, population movements, etc., has worsened the epidemic situation and TB has become a key cause of death worldwide.3−5 Two of the most prominent challenges in eradicating TB are the difficult diagnosis and the appearance of multidrug resistant mycobacteria strains.6 M. tuberculosis is a challenging parasitic pathogen, which upon infection can be phagocytized by macrophages and remain dormant until activated. The composition of the bacterial cell wall protects the internalized pathogen, which can further induce macrophage apoptosis.7 The cell wall also serves as a protective barrier to prevent antitubercular agents from permeating into the bacterial cytoplasm.8 One of the first-line drugs, isoniazid (INH), has been employed for more than 60 years as a preferred choice in tuberculosis chemotherapy.9 INH can be converted into an electrophilic species through activation by M. tuberculosis KatG, leading to inhibition of the biosynthesis of mycolic acid, an important component of the M. tuberculosis cell wall.10−13 However, INH has a serious side effect due to its toxicity toward hepatocytes, which decreases the therapeutic efficacy and limits the effectiveness of INH.14 Thus, rapid and selective drug delivery, achieving high local concentrations and minimizing side effects, is necessary and urgent. Targeting agents based on carbohydrates are in this context attractive, taking advantage of selective binding and transport © XXXX American Chemical Society
processes that are mediated by carbohydrate entities. In mycobacteria, the disaccharide α,α-trehalose is a known, essential precursor for cell-wall glycolipids, and is translocated across the plasma membrane in monomycolate form. Selective uptake of trehalose was also recently shown to occur in mycobacteria, and trehalose conjugates have been used to transport, for example, fluorophores into the cells.15−18 The general treatment plan for tuberculosis is multidrug chemotherapy, which usually takes several months to complete.19 Additionally, the adverse effect and premature degradation of drugs influence the therapeutic efficacy.20 In this context, controlled drug delivery systems based on engineered nanocarriers offer an attractive alternative strategy. Nanomaterials such as polymersomes, solid lipid nanoparticles, and lipsomes have been reported as delivery vehicles for antitubercular drugs, albeit devoid of targeting devices.21−24 These materials can show high loading capacity, incorporate hydrophilic and hydrophobic cargos, and be amenable to various ways of administration, including oral uptake and inhalation.25 However, some challenges still remain, e.g., poor chemical stability of liposomes and lipid nanoparticles,26 and fast biodegradability of polymeric nanoparticles.27,28 Mesoporous silica nanoparticles (MSNs) are another drug delivery platform where some of these drawbacks can be avoided.29,30 In addition, MSNs can be prepared with different surface- and internal functionalities, allowing for the incorporation of a wide Received: June 24, 2015 Accepted: October 27, 2015
A
DOI: 10.1021/acsbiomaterials.5b00274 ACS Biomater. Sci. Eng. XXXX, XXX, XXX−XXX
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ACS Biomaterials Science & Engineering range of features that for example enable targeted and controlled release under specific environmental conditions.31,32 Only a few studies on MSN-based transport of antitubercular drugs to M. tuberculosis have been reported. For example, Clemens et al. designed PEI-coated MSNs functionalized with pH-responsive “valves” for the release of rifampicin to M. tuberculosis-infected macrophages.33 The MSNs serve as a multivalent scaffold, presenting multiple copies of trehalose ligand and thus enhancing the binding affinity. This multivalent presentation of sugars have been developed in other glyconanomaterials systems such as carbon nanotubes,34 gold nanoparticles,35−37 magnetic nanoparticles,38 and silica nanoparticles,39,40 and have been applied in biosensing,41 bioimaging, and drug delivery.42 Herein, we describe the synthesis of a drug delivery system based on trehalose-functionalized MSNs. The multivalent glyconanoparticles were then encapsulate with INH, and were subseuquently evaluated for selectivity and antibacterial activity toward M. smegmatis mc2 651.
Scheme 1. Synthetic Route of INH-Loaded Glyconanoparticles
2. MATERIALS AND METHODS 2.1. Materials. Hexadecyltrimethylammonium bromide (CTAB, 99%+) was purchased from Fluka, D-(+)-trehalose dihydrate was obtained from Alfa Aesar, tetraethyl orthosilicate (TEOS), sodium hydroxide (NaOH) and isoniazid (INH, 99%+) were purchased from Sigma-Aldrich. All reagents were used as received without further purification. Transmission electron microscopy (TEM) images were obtained from a Phillips EM-400T TEM microscope operating at 100 kV. Samples were dispersed in ethanol and dropped on Cu grids, which were dried in air overnight. Nitrogen adsorption−desorption isotherms were peformed on a Micromeritics ASAP2010 at 77.3 K under continuous adsorption conditions. The surface area was determined by Brunauer−Emmett−Teller (BET) analysis. The pore size distribution plots and pore volume were obtained by Barrett− Joyner−Halenda (BJH) analysis of the adsorption−desorption isotherms. FT-IR spectra were measured with a BioRad FTS-375 IR spectrometer. Thermogravimetric analyses (TGA) were recorded on a Mettler-Toledo TGA/SDTA 851e. All samples were first heated to 100 °C and then cooled to 50 °C under dry nitrogen gas to remove all adsorbed volatiles before measurements. Dynamic light scattering and zeta potential were measured with a Nanozeta (zetasizer) instrument. All samples were dispersed in water for recording. UV absorbance spectra were recorded using a Cary 300 spectrophotometer. Perfluorophenylazide silane (PFPA-Silane) was synthesized following previously developed procedure (Scheme S1, Figures S1 and S2).43 2.2. Synthesis of MSNs. CTAB (0.25 g, 0.7 mmol) was dissolved in distilled water (120 mL) that contained NaOH aqueous solution (2 M, 0.875 mL), and the temperature was heated to 80 °C. TEOS (1.25 mL) was added into the solution, and the mixture was allowed to stir for 2 h. The formed solid product was removed by filtration and dried under vacuum. The crude nanoparticles were repeatedly refluxed in acidic methanol solution, followed by filtration, until no CTAB was detected by FT-IR. The resulting particles were filtered and extensively washed with water and methanol, and dried under vacuum at 50 °C. 2.3. Synhesis of PFPA-functionalized MSNs (M-PFPA Particles). MSNs (150 mg) were dispersed in a solution of PFPAsilane in toluene (10 mg/mL, 10 mL), and heated at 80 °C overnight. The functionalized MSNs were collected by centrifugation, washed with toluene and ethanol, and dried under vacuum (Scheme 1). 2.4. Synthesis of Trehalose-Functionalized MSNs (M-PFPATre particles). A previously reported method for carbohydrate functionalization was adopted.44 A homogeneous suspension of MPFPA particles in acetone (4.0 mg/mL, 0.5 mL) was dispersed in a flat-bottom dish, to which an aqueous solution of trehalose (4.0 mg/ mL, 0.5 mL) was added. The mixture was covered with a 280 nm longpath optical filter and irradiated with a medium-pressure Hg lamp for 30 min under vigorous stirring. The MSNs were isolated by centrifugation at 7000 rpm for 20 min, and excess carbohydrate was
removed by dialysis for 24 h. The target particles were finally obtained by centrifugation and drying under vacuum (78%). 2.5. Isoniazid Loading. M-PFPA-Tre particles (80 mg) were dispersed in INH solution (8 mg/mL, 10 mL), and the mixture was stirred for 2 days at r.t. The particles were collected by centrifugation, washed with water and dried under vacuum to give M-PFPA-Tre-INH glyconanoparticles (91%). 2.6. INH Release from M-PFPA-Tre-INH Particles. M-PFPATre-INH samples in water (1.0 mg/mL, pH ∼6.8) were incubated at 37 °C under gentle stirring. At time intervals of 1/3, 1, 2, 4, 6, 8, 10, 12, 24, and 48 h, the particles were removed by centrifugation, and the INH released in the collected upper layer solutions was quantitated by spectrophotometry at 263 nm. 2.7. Incubation of MSNs with M. smegmatis. M. smegmatis strain mc2 651 was inoculated overnight in enriched Middlebrook 7H9 broth at 37 °C while shaking at 180 rpm. The resulting culture was reinoculated in fresh, enriched Middlebrook 7H9 medium and grown until an OD650 of 0.3 was attained, corresponding to ∼9 × 107 bacteria cells. An aliquot (1 mL) of this bacterial suspension was withdrawn and serially diluted (100-fold) in Middlebrook 7H9 broth. Aliquots of the diluted solution (100 μL) were incubated for 48 h with different concentrations of MSNs, M-PFPA, M-PFPA-Tre and M-PFPA-TreINH particles (5, 4.5, 4.0, 3.0, 1.5, and 0.5 mg/mL). A control material obtained by mixing MSNs and INH directly (M-INH particles) was also incubated with M. smegmatis for comparison. 2.8. Colony Counting Assay to Determine Bacterial Viability. Aliquots (10 μL) of the particle-treated bacterial suspensions were withdrawn and serially diluted (1 × 105-fold) in Middlebrook 7H9 broth. The diluted solution (50 μL) was spread out on Middlebrook 7H10 agar plates, and colonies were counted (reported as log CFU/ mL) after 72 h of incubation at 37 °C.
3. RESULTS AND DISCUSSION 3.1. Synthesis and Characterization of Nanoparticles. The functionalized nanoparticles were synthesized from MSNs prepared by the base-catalyzed sol−gel method of Lin and coworkers.45,46 TEM images revealed that the resulting MSNs were approximately spherical, and were 120 ± 22 nm in size by TEM (Figure 1a) and 154 ± 32 nm by DLS (Figure S3). The MSNs were subsequently functionalized with PFPA-silane to establish a surface layer of perfluorophenylazide (Scheme 1). B
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Tre particles showed an additional weight loss of 7.6% (76 μg/ mg) compared to the M-PFPA, indicating that trehalose was indeed conjugated to the surface. Furthermore, zeta potential analyses indicated that the M-PFPA-Tre-INH particles showed better dispersibility than the nonconjugated nanoparticles (Figure 2d). 3.2. Release Profile. The INH loading was carried out by dispersion of M-PFPA-Tre particles (80 mg) and INH in water (8 mg/mL, 10 mL), yielding 170 μg of INH per mg of MSNs. Release of INH from the trehalose-functionalized MSNs was monitored from incubation of M-PFPA-Tre-INH particles in water under stirring at 37 °C, followed by centrifugation at predetermined intervals. As can be seen from Figure 3, the INH
Figure 1. TEM images of (a) MSNs and (b) M-PFPA-Tre-INH particles.
The resulting M-PFPA particles were then subjected to nitrenemediated photoligation of trehalose under UV activation,47,48 yielding carbohydrate-functionalized M-PFPA-Tre nanoparticles. Finally, drug-loaded M-PFPA-Tre-INH glyconanoparticles were obtained through dispersion in INH solution (Figure 1b). The structure and functionalization of the nanoparticles were further characterized. As shown in Figure 2a, the MSNs
Figure 3. Percent INH released from M-PFPA-Tre-INH at the fixed time points. The inset is the enlarged image of the percent INH released from particles at the beginning of 8 h.
release followed a two-phase kinetic process: an initial burst release during the first few hours, most probably attributed to the loss of INH adsorbed at the external surface;22 and a sustained release process over the following 40 h. In principle, the two-phase release kinetics may be advantageous, where a localized, high initial concentration of INH leads to a more efficient bactericidal effect, strengthened and consolidated by the sustained release. The release study was repeated using pH 6 PBS buffer to simulate the intracellular environment.52 The release profile (Figure S4) is very similar to that in water. 3.3. The Antibacterial Activity of Nanoparticles. M. smegmatis mc2 651, an INH-resistant mycobacterium, was used in the studies. The effects of the particles on M. smegmatis mc2 651 were evaluated by TEM. As shown in Figure 4, the TEM images displayed clear interactions between the trehalosefunctionalized particles and the bacteria. The M-PFPA-Tre glyconanoparticles (Figure 4c) were bound more efficiently to M. smegmatis mc2 651 than either the MSNs or the M-PFPA particles (Figure 4a, b). Comparing the two antibacterial drug carriers, M-INH and M-PFPA-Tre-INH (Figure 4d, e), a considerably higher amount of M-PFPA-Tre-INH nanoparticles were observed on M. smegmatis mc2 651, this may be attributed to the higher degree of bacterial lysis in the case of M-PFPA-Tre-INH, which released intracellular substrates that caused increased adhesion/binding to nanoparticles. To assess the drug delivery and antibacterial activity of the M-PFPA-Tre-INH glyconanoparticles toward M. smegmatis mc2 651, different concentrations of particles were incubated with the bacteria for 2 days, and the survival colonies were counted. Free INH, nonfunctionalized MSNs, M-PFPA and MPFPA-Tre particles were treated the same way. INH-loaded, nonfunctionalized MSNs were in addition tested for evaluating
Figure 2. (a) Nitrogen adsorption−desorption isotherms of MSNs and its pore size distributions (insert); (b) FT-IR spectra of MSNs, MPFPA and M-PFPA-Tre; (c) thermogravimetric analysis (TGA) of MPFPA and M-PFPA-Tre; (d) zeta potentials of nanoparticles.
presented the typical adsorption−desorption isotherm, indicating a mesoporous structure. The particle surface area and pore size distributions were analyzed by BET and BJH, resulting in a surface area of 740 m2/g and an average pore size of 2.8 nm, respectively. FT-IR (Figure 2b) was used to monitor the removal of CTAB of the crude MSNs, as well as the azide group in the M-PFPA and M-PFPA-Tre particles. The absence of a CTAB signal around 3000 cm−1 indicated that the template was completely removed,49 which is of importance because CTAB is toxic to bacteria, and if left in the mesoporous silica, could make the material antimicrobial.50,51 Modification of the MSNs with PFPA-silane resulted in an azide signal at 2135 cm−1, further supported by signals at 1500 and 1660 cm−1. Upon photoinitiation, disappearance of the azide signal indicated ligation of trehalose to the nanoparticle surface, and TGA was performed to estimate the amount of conjugated trehalose to the particles. As shown in Figure 2c, the M-PFPAC
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kinetics, with initial burst release followed by slow, sustained release. The antibacterial activity of the resulting M-PFPA-TreINH particles toward M. smegmatis mc2 651 was confirmed by antimicrobial susceptibility tests. Compared with nonfunctionalized nanoparticles and free INH, the glyconanomaterial containers showed increased ability to killing bacteria, displaying the advantageous target function of trehalose to facilitate the localized release of INH. These materials not only show higher bactericidal effects toward Mycobacteria, but in principle demonstrate high potential for reviving the antibacterial effects of common antibiotics, a venue we are currently pursuing.
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ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsbiomaterials.5b00274. Synthesis and 1 H NMR, 13 C NMR analysis of perfluorophenylazide silane, DLS results of MSNs and M-PFPA-Tre-INH, percent INH release from M-PFPATre-INH at fixed time points at pH 6 (PDF)
Figure 4. TEM images of (a) MSNs, (b) M-PFPA, (c) M-PFPA-Tre, (d) M-INH, and (e) M-PFPA-Tre-INH particles incubated with M. smegmatis mc2 651 for 48 h.
the mycobacterial targeting effect of trehalose. The results in Figure 5 showed that the nonfunctionalized MSNs, M-PFPA
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AUTHOR INFORMATION
Corresponding Authors
*E-mail:
[email protected]. *E-mail:
[email protected]. Phone: +46 8 7906915. Fax: +46 9 7912333. Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS The study was in part supported the National Institutes of Health (R01GM080295, R21AI109896 to M. Y.). J. Z., N. K., and Y. S. thank the China Scholarship Council for special scholarship awards.
Figure 5. Log in CFU/mL of different concentrations of bare MSNs, M-PFPA, M-PFPA-Tre, M-PFPA, and M-PFPA-Tre-INH after treating with M. smegmatis mc2 651.
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and M-PFPA-Tre particles had only minor fluctuations within the range of tested concentrations, with no obvious toxicity on M. smegmatis mc2 651. In contrast, the viability of M. smegmatis declined with increasing concentrations of M-PFPA-Tre-INH and M-INH particles. The glycosylated nanoparticles produced the largest bactericidal effect with complete growth inhibition within 3−4 mg/mL of M-PFPA-Tre-INH particles, whereas the M-INH preparation was effective at higher concentrations of 4.5−5 mg/mL. These results indicate that trehalose conjugated at the surface of mesoporous silica nanoparticles indeed played a targeting role on the bacteria. In addition, the free INH released from 3−4 mg/mL of the M-PFPA-Tre-INH particles corresponds to 390−520 μg/mL according to the INH-release profile in vitro, whereas the minimum inhibitory concentration (MIC) of free INH toward M. smegmatis mc2 651 was 1.0−1.5 mg/mL. Thus, the combined targeting and localized release of INH lead to improved bactericidal action.
REFERENCES
(1) Dye, C. Global epidemiology of tuberculosis. Lancet 2006, 367 (9514), 938−940. (2) Global Tuberculosis Report 2014; WHO Press: Geneva, Switzerland2014. (3) Corbett, E. L.; Watt, C. J.; Walker, N. The growing burden of tuberculosis: Global trends and interactions with the HIV epidemic. Arch. Intern. Med. 2003, 163 (9), 1009−1021. (4) Dye, C.; Watt, C. J.; Bleed, D. M.; Hosseini, S.; Raviglione, M. C. Evolution of tuberculosis control and prospects for reducing tuberculosis incidence, prevalence, and deaths globally. J. Am. Med. Assoc. 2005, 293 (22), 2767−2775. (5) Walls, T.; Shingadia, D. Global epidemiology of paediatric tuberculosis. J. Infect. 2004, 48 (1), 13−22. (6) Dye, C.; Espinal, M. A.; Watt, C. J.; Mbiaga, C.; Williams, B. G. Worldwide Incidence of Multidrug-Resistant Tuberculosis. J. Infect. Dis. 2002, 185 (8), 1197−1202. (7) Dao, D. N.; Kremer, L.; Guérardel, Y.; Molano, A.; Jacobs, W. R.; Porcelli, S. A.; Briken, V. Mycobacterium tuberculosis Lipomannan Induces Apoptosis and Interleukin-12 Production in Macrophages. Infect. Immun. 2004, 72 (4), 2067−2074. (8) Bansal-Mutalik, R.; Nikaido, H. Mycobacterial outer membrane is a lipid bilayer and the inner membrane is unusually rich in diacyl phosphatidylinositol dimannosides. Proc. Natl. Acad. Sci. U. S. A. 2014, 111 (13), 4958−4963. (9) Johnsson, K.; King, D. S.; Schultz, P. G. Studies on the Mechanism of Action of Isoniazid and Ethionamide in the Chemo-
4. CONCLUSIONS In summary, we have synthesized isoniazid-loaded mesoporous silica nanoparticles, functionalized by trehalose for selective targeting and killing of the INH-resistant mycobacterium. The glyconanomaterials were composed of ∼8% trehalose and could be loaded to contain 170 μg/mg of INH. From in vitro studies, INH was released from the nanocarriers following two-phase D
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ACS Biomaterials Science & Engineering therapy of Tuberculosis. J. Am. Chem. Soc. 1995, 117 (17), 5009− 5010. (10) Lei, B.; Wei, C.-J.; Tu, S.-C. Action Mechanism of Antitubercular Isoniazid. J. Biol. Chem. 2000, 275 (4), 2520−2526. (11) Anbazhagan, P.; Harijan, R. K.; Kiema, T. R.; Janardan, N.; Murthy, M. R. N.; Michels, P. A. M.; Juffer, A. H.; Wierenga, R. K. Phylogenetic relationships and classification of thiolases and thiolaselike proteins of Mycobacterium tuberculosis and Mycobacterium smegmatis. Tuberculosis 2014, 94 (4), 405−412. (12) Amos, R. I. J.; Gourlay, B. S.; Schiesser, C. H.; Smith, J. A.; Yates, B. F. A mechanistic study on the oxidation of hydrazides: application to the tuberculosis drug isoniazid. Chem. Commun. 2008, 14, 1695−1697. (13) Zhao, X.; Hersleth, H.-P.; Zhu, J.; Andersson, K. K.; Magliozzo, R. S. Access channel residues Ser315 and Asp137 in Mycobacterium tuberculosis catalase-peroxidase (KatG) control peroxidatic activation of the pro-drug isoniazid. Chem. Commun. 2013, 49 (99), 11650− 11652. (14) van Hest, R.; Baars, H.; Kik, S.; van Gerven, P.; Trompenaars, M.-C.; Kalisvaart, N.; Keizer, S.; Borgdorff, M.; Mensen, M.; Cobelens, F. Hepatotoxicity of Rifampin-Pyrazinamide and Isoniazid Preventive Therapy and Tuberculosis Treatment. Clin. Infect. Dis. 2004, 39 (4), 488−496. (15) Kalscheuer, R.; Weinrick, B.; Veeraraghavan, U.; Besra, G. S.; Jacobs, W. R. Trehalose-recycling ABC transporter LpqY-SugA-SugBSugC is essential for virulence of Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. U. S. A. 2010, 107 (50), 21761−21766. (16) Urbanek, B. L.; Wing, D. C.; Haislop, K. S.; Hamel, C. J.; Kalscheuer, R.; Woodruff, P. J.; Swarts, B. M. Chemoenzymatic Synthesis of Trehalose Analogues: Rapid Access to Chemical Probes for Investigating Mycobacteria. ChemBioChem 2014, 15 (14), 2066− 2070. (17) Swarts, B. M.; Holsclaw, C. M.; Jewett, J. C.; Alber, M.; Fox, D. M.; Siegrist, M. S.; Leary, J. A.; Kalscheuer, R.; Bertozzi, C. R. Probing the Mycobacterial Trehalome with Bioorthogonal Chemistry. J. Am. Chem. Soc. 2012, 134 (39), 16123−16126. (18) Backus, K. M.; Boshoff, H. L.; Barry, C. S.; Boutureira, O.; Patel, M. K.; D’Hooge, F.; Lee, S. S.; Via, L. E.; Tahlan, K.; Barry, C. E.; Davis, B. G. Uptake of unnatural trehalose analogs as a reporter for Mycobacterium tuberculosis. Nat. Chem. Biol. 2011, 7 (4), 228−235. (19) Bass, J. B.; Farer, L. S.; Hopewell, P. C.; O’Brien, R.; Jacobs, R. F.; Ruben, F.; Snider, D. E.; Thornton, G. Treatment of tuberculosis and tuberculosis infection in adults and children. American Thoracic Society and The Centers for Disease Control and Prevention. Am. J. Respir. Crit. Care Med. 1994, 149 (5), 1359−1374. (20) Agal, S.; Baijal, R.; Pramanik, S.; Patel, N.; Gupte, P.; Kamani, P.; Amarapurkar, D. Monitoring and management of antituberculosis drug induced hepatotoxicity. J. Gastroenterol. Hepatol. 2005, 20 (11), 1745−1752. (21) Gadde, S.; Even-Or, O.; Kamaly, N.; Hasija, A.; Gagnon, P. G.; Adusumilli, K. H.; Erakovic, A.; Pal, A. K.; Zhang, X.-Q.; Kolishetti, N.; Shi, J.; Fisher, E. A.; Farokhzad, O. C. Development of Therapeutic Polymeric Nanoparticles for the Resolution of Inflammation. Adv. Healthcare Mater. 2014, 3 (9), 1448−1456. (22) Zhu, M.; Wang, H. X.; Liu, J. Y.; He, H. L.; Hua, X. G.; He, Q. J.; Zhang, L. X.; Ye, X. J.; Shi, J. L. A mesoporous silica nanoparticulate/beta-TCP/BG composite drug delivery system for osteoarticular tuberculosis therapy. Biomaterials 2011, 32 (7), 1986− 1995. (23) Griffiths, G.; Nyström, B.; Sable, S. B.; Khuller, G. K. Nanobeadbased interventions for the treatment and prevention of tuberculosis. Nat. Rev. Microbiol. 2010, 8 (11), 827−834. (24) Cronje, L.; Warren, R.; Klumperman, B. pH-dependent adhesion of mycobacteria to surface-modified polymer nanofibers. J. Mater. Chem. B 2013, 1 (48), 6608−6618. (25) Mane, S. R.; Rao N, V.; Chatterjee, K.; Dinda, H.; Nag, S.; Kishore, A.; Sarma, J. D.; Shunmugam, R. A unique polymeric nanocarrier for anti-tuberculosis therapy. J. Mater. Chem. 2012, 22 (37), 19639−19642.
(26) Foradada, M.; Pujol, M. D.; Bermúdez, J.; Estelrich, J. Chemical degradation of liposomes by serum components detected by NMR. Chem. Phys. Lipids 2000, 104 (2), 133−148. (27) Lam, K. H.; Schakenraad, J. M.; Esselbrugge, H.; Feijen, J.; Nieuwenhuis, P. The effect of phagocytosis of poly(L-lactic acid) fragments on cellular morphology and viability. J. Biomed. Mater. Res. 1993, 27 (12), 1569−1577. (28) Marques, A. P.; Reis, R. L.; Hunt, J. A. Cytokine secretion from mononuclear cells cultured in vitro with starch-based polymers and poly-L-lactide. J. Biomed. Mater. Res. 2004, 71 (3), 419−429. (29) He, Q.; Shi, J. Mesoporous silica nanoparticle based nano drug delivery systems: synthesis, controlled drug release and delivery, pharmacokinetics and biocompatibility. J. Mater. Chem. 2011, 21 (16), 5845−5855. (30) Chen, Y.; Chen, H.; Shi, J. In Vivo Bio-Safety Evaluations and Diagnostic/Therapeutic Applications of Chemically Designed Mesoporous Silica Nanoparticles. Adv. Mater. 2013, 25 (23), 3144−3176. (31) Mura, S.; Nicolas, J.; Couvreur, P. Stimuli-responsive nanocarriers for drug delivery. Nat. Mater. 2013, 12 (11), 991−1003. (32) Porta, F.; Lamers, G. E. M.; Morrhayim, J.; Chatzopoulou, A.; Schaaf, M.; den Dulk, H.; Backendorf, C.; Zink, J. I.; Kros, A. Folic Acid-Modified Mesoporous Silica Nanoparticles for Cellular and Nuclear Targeted Drug Delivery. Adv. Healthcare Mater. 2013, 2 (2), 281−286. (33) Clemens, D. L.; Lee, B.-Y.; Xue, M.; Thomas, C. R.; Meng, H.; Ferris, D.; Nel, A. E.; Zink, J. I.; Horwitz, M. A. Targeted Intracellular Delivery of Antituberculosis Drugs to Mycobacterium tuberculosisInfected Macrophages via Functionalized Mesoporous Silica Nanoparticles. Antimicrob. Agents Chemother. 2012, 56 (5), 2535−2545. (34) Kong, N.; Shimpi, M. R.; Park, J. H.; Ramström, O.; Yan, M. Carbohydrate conjugation through microwave-assisted functionalization of single-walled carbon nanotubes using perfluorophenyl azides. Carbohydr. Res. 2015, 405, 33−38. (35) Wang, X.; Ramström, O.; Yan, M. Dynamic light scattering as an efficient tool to study glyconanoparticle-lectin interactions. Analyst 2011, 136 (20), 4174−4178. (36) Wang, X.; Matei, E.; Gronenborn, A. M.; Ramström, O.; Yan, M. Direct Measurement of Glyconanoparticles and Lectin Interactions by Isothermal Titration Calorimetry. Anal. Chem. 2012, 84 (10), 4248−4252. (37) Jayawardena, H. S. N.; Wang, X.; Yan, M. Classification of Lectins by Pattern Recognition Using Glyconanoparticles. Anal. Chem. 2013, 85 (21), 10277−10281. (38) Liu, L. H.; Dietsch, H.; Schurtenberger, P.; Yan, M. Photoinitiated Coupling of Unmodified Monosaccharides to Iron Oxide Nanoparticles for Sensing Proteins and Bacteria. Bioconjugate Chem. 2009, 20 (7), 1349−1355. (39) Tong, Q.; Wang, X.; Wang, H.; Kubo, T.; Yan, M. Fabrication of Glyconanoparticle Microarrays. Anal. Chem. 2012, 84 (7), 3049−3052. (40) Wang, X.; Matei, E.; Deng, L.; Koharudin, L.; Gronenborn, A. M.; Ramström, O.; Yan, M. Sensing lectin-glycan interactions using lectin super-microarrays and glycans labeled with dye-doped silica nanoparticles. Biosens. Bioelectron. 2013, 47 (0), 258−264. (41) Hao, N.; Neranon, K.; Ramström, O.; Yan, M. Glyconanomaterials for biosensing applications. Biosens. Bioelectron., 2015, DOI: 10.1016/j.bios.2015.07.031. (42) Chen, X.; Ramströ m, O.; Yan, M. Glyconanomaterials: Emerging applications in biomedical research. Nano Res. 2014, 7 (10), 1381−1403. (43) Wang, H.; Ren, J.; Hlaing, A.; Yan, M. Fabrication and antifouling properties of photochemically and thermally immobilized poly(ethylene oxide) and low molecular weight poly(ethylene glycol) thin films. J. Colloid Interface Sci. 2011, 354 (1), 160−167. (44) Wang, X.; Ramström, O.; Yan, M. Dye-doped silica nanoparticles as efficient labels for glycans. Chem. Commun. 2011, 47 (14), 4261−4263. (45) Zhao, Y.; Trewyn, B. G.; Slowing, I. I.; Lin, V. S. Y. Mesoporous Silica Nanoparticle-Based Double Drug Delivery System for GlucoseE
DOI: 10.1021/acsbiomaterials.5b00274 ACS Biomater. Sci. Eng. XXXX, XXX, XXX−XXX
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ACS Biomaterials Science & Engineering Responsive Controlled Release of Insulin and Cyclic AMP. J. Am. Chem. Soc. 2009, 131 (24), 8398−8400. (46) Wu, S.-H.; Mou, C.-Y.; Lin, H.-P. Synthesis of mesoporous silica nanoparticles. Chem. Soc. Rev. 2013, 42 (9), 3862−3875. (47) Jayawardena, H. S. N.; Jayawardana, K. W.; Chen, X.; Yan, M. Maltoheptaose promotes nanoparticle internalization by Escherichia coli. Chem. Commun. 2013, 49 (29), 3034−3036. (48) Wang, X.; Matei, E.; Deng, L.; Ramström, O.; Gronenborn, A. M.; Yan, M. Multivalent glyconanoparticles with enhanced affinity to the anti-viral lectin Cyanovirin-N. Chem. Commun. 2011, 47 (30), 8620−8622. (49) Chen, M. J.; Huang, C. S.; He, C. S.; Zhu, W. P.; Xu, Y. F.; Lu, Y. F. A glucose-responsive controlled release system using glucose oxidase-gated mesoporous silica nanocontainers. Chem. Commun. 2012, 48 (76), 9522−9524. (50) Salt, W. G.; Wiseman, D. The relation between the uptake of cetyltri-methylammonium bromide by Escherichia coli and its effects on cell/growth and viability. J. Pharm. Pharmacol. 1970, 22 (4), 261− 264. (51) Hao, N.; Chen, X.; Jayawardana, K. W.; Wu, B.; Sundhoro, M.; Yan, M. Shape control of mesoporous silica nanomaterials templated with dual cationic surfactants and their antibacterial activities. Biomater. Sci., 2015, DOI: 10.1039/C5BM00197H. (52) Pieters, J. Entry and survival of pathogenic mycobacteriain macrophages. Microbes Infect. 2001, 3 (3), 249−255.
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DOI: 10.1021/acsbiomaterials.5b00274 ACS Biomater. Sci. Eng. XXXX, XXX, XXX−XXX
