Biomolecular condensation of the microtubule-associated protein tau.

Cells contain multiple compartments dedicated to the regulation and control of biochemical reactions. Cellular compartments that are not surrounded by membranes can rapidly form and dissolve in response to changes in the cellular environment. The physicochemical processes that underlie the formation of non-membrane-bound compartments in vivo are connected to liquid-liquid phase separation of proteins and nucleic acids in vitro. Recent evidence suggests that the protein tau, which plays an important role in Alzheimer's disease and other neurodegenerative disorders, phase separates in solution, forms tau phases with microtubules, and associates with phase-separated RNA-binding protein granules in cells. Here we review the experimental evidence that supports the ability of tau to phase separate in solution and form biomolecular condensates in cells. As for other disease-relevant proteins, the physiological and pathological functions of tau are tightly connected - through loss of normal function or gain of toxic function - and we therefore discuss how tau phase separation plays a role for both, and with respect to different cellular functions of tau

ASL MRI and 18F-FDG-PET in autoimmune limbic encephalitis: clues from two paradigmatic cases

Background: Autoimmune limbic encephalitis (LE) is a neurological condition characterized by seizures and cognitive dysfunction. Fluorine-18 fluorodeoxyglucose (18F-FDG-PET) has recently proved to be an important diagnostic tool in this condition since it may highlight brain metabolism abnormalities in a very early stage of the disease. Two main 18F-FDG-PET patterns have been described: the mixed hypermetabolic/hypometabolic and the neurodegenerative one. Arterial spin labeling (ASL) is an MRI technique showing brain perfusion, rarely used in autoimmune neurological conditions. The aim of the present study was to study patients with LE with both techniques, in order to compare their results. Methods: Two patients with LE underwent to 18F-FDG-PET and ASL MRI scans using the pseudo-continuous arterial spin labeling (PCASL) technique. Areas of altered perfusion and metabolism were analyzed by visual inspection, and findings were compared between the two techniques. Results: In the first patient, a relapsing LGI-1 LE, right hippocampal hypermetabolism was detected by 18F-FDG-PET (mixed hypermetabolic/hypometabolic pattern), while ASL MRI showed right hippocampal increased perfusion. In the second patient, a seronegative LE, 18F-FDG-PET scan detected a left hemispheric hypoperfusion (neurodegenerative pattern) and ASL MRI yielded similar results. The two 18F-FDG-PET patterns of altered metabolism were similarly detected by ASL imaging. Conclusion: ASL and 18F-FDG-PET findings are strongly concordant in LE. ASL imaging was able to detect the two main 18F-FDG-PET patterns previously described in patients with LE

The Role of Amygdala in Self-Conscious Emotions in a Patient With Acquired Bilateral Damage

Shame plays a fundamental role in the regulation of our social behavior. One intriguing question is whether amygdala might play a role in processing this emotion. In the present single-case study, we tested a patient with acquired damage of bilateral amygdalae and surrounding areas as well as healthy controls on shame processing and other social cognitive tasks. Results revealed that the patient\u2019s subjective experience of shame, but not of guilt, was more reduced than in controls, only when social standards were violated, while it was not different than controls in case of moral violations. The impairment in discriminating between normal social situations and violations also emerged. Taken together, these findings suggest that the role of the amygdala in processing shame might reflect its relevance in resolving ambiguity and uncertainty, in order to correctly detect social violations and to generate shame feelings

Lysine/RNA-interactions drive and regulate biomolecular condensation.

Cells form and use biomolecular condensates to execute biochemical reactions. The molecular properties of non-membrane-bound condensates are directly connected to the amino acid content of disordered protein regions. Lysine plays an important role in cellular function, but little is known about its role in biomolecular condensation. Here we show that protein disorder is abundant in protein/RNA granules and lysine is enriched in disordered regions of proteins in P-bodies compared to the entire human disordered proteome. Lysine-rich polypeptides phase separate into lysine/RNA-coacervates that are more dynamic and differ at the molecular level from arginine/RNA-coacervates. Consistent with the ability of lysine to drive phase separation, lysine-rich variants of the Alzheimer's disease-linked protein tau undergo coacervation with RNA in vitro and bind to stress granules in cells. Acetylation of lysine reverses liquid-liquid phase separation and reduces colocalization of tau with stress granules. Our study establishes lysine as an important regulator of cellular condensation

Multimodal CT pc-ASPECTS in infratentorial stroke: diagnostic and prognostic value

Background and purpose: Diagnosis of posterior circulation stroke may be challenged. National Institutes of Health Stroke Scale (NIHSS) and brain imaging (non-contrast brain computed tomography-CT) are used for diagnosis; evaluation on posterior circulation stroke remains a limit of NIHSS, and the value of non-contrast CT (NCCT) is limited due to artifacts caused by the bones of the base of the skull. We tested the validity and prognostic value of posterior circulation Alberta Stroke Program Early CT Score (pc-ASPECTS) in patients with posterior circulation stroke. Methods: Pc-ASPECTS allots the posterior circulation 10 points. We studied 50 patients with posterior circulation stroke. We applied pc-ASPECTS to NCCT, CT angiography, and CT Perfusion. We evaluated the correlation of pc-ASPECT with outcome parameters for stroke. Results: Out of 50 patients, CTP showed abnormalities in 34 cases. The pc-ASPECT score calculated on brain CT and on the brain CT + angio CT had a sensibility of 24%, calculated on brain CT, angio CT and CTPerfusion gain a sensibility of 72%. Pc-ASPECT MTT resulted to be the more reliable parameter: outcome given by NIHSS score at discharge, mRS at discharge, and at 3 months was more severe in patients with Pc-ASPECT MTT alteration. Outcome given by NIHSS score at discharge and mRS at discharge and 1 at 3 months was more severe in patients with higher NIHSS score at admission. Conclusion: We evaluated the usefulness of pc-ASPECTS on CTP in predicting functional outcome in acute posterior circulation stroke that appears to be a powerful marker for predicting functional outcome

A longitudinal study of brain atrophy and cognitive disturbances in the early phase of relapsing-remitting multiple sclerosis

Objective—(a) To establish whether the cognitive decline of the early phase of relapsing-remitting multiple sclerosis depends on the progression of the burden of disease, or on the loss of brain parenchyma, or is influenced by both; (b) to monitor the loss of brain parenchyma in the early phase of the disease; and (c) to examine its possible relation with the progression of physical disability. Methods—For 2 years 53 patients with clinically definite relapsing-remitting multiple sclerosis with disease duration 1–5 years and expanded disability status scale<5.0 at baseline were monitored.The neuropsychological performances, the psychological functioning, the neurological impairment, and the disability have beenassessedatbaselineandafter2years. Patients also underwent PD/T2 and T1 weighted brain MRI.T2 and T1 lesion volumes were measured by a semiautomatic technique. Quantification of brain parenchymal volumes was obtained using a highly reproducible computerised interactive program. The relation between cognitive impairment and MRI findings has been investigated by partial correlation and stepwise multiple regression analyses excluding the eVects of age, education, anxiety, depression, and total days of steroid use. Results—In the 2 years of the study the meanchangeforT2andT1lesionvolumes and brain parenchymal volumes were +1.7 ml (95% confidence interval (95% CI) 1.3– 2.2, p=0.005, (29.8%); +0.2 ml, 95% CI 0.15–0.26, p=0.004, (25%); and –32.3 ml, 95% CI 24.2–42.3, p<0.0001, (2.7%), respectively. Overall, 14 patients (26.4%) were judged to be cognitively impaired at baseline and 28 (52.8%) at the end of the follow up. Of the 18 neuropsychological tests and subtests employed in the study, patients with multiple sclerosis failed 5.8 (SD 2.3) tests at the baseline and 8.4 (SD 2.9) (p<0.0001) tests at the end of the study. When the cognitive changes were examined in individual patients, five (9.4%) of them were considered cognitively improved, 33 (62.3%) remained stable, and 15 (28.3%) worsened over 2 years. T2 and T1 volume changes in improved, stable, and worsened patients did not show any significant diVerence, whereas brain parenchymal volume decrease in cognitively worsened patients was significantly greater (−66 ml (5.4%), 95% CI 37–108.9, p=0.0031). The cognitive impairment was independently predicted over 2 years only by the change of brain parenchymal volumes (R=0.51, p=0.0003). Ten patients (18.9%), who worsened by one or more points in the EDSS during the follow up period had significant decreases in brain parenchymal volumes (−99 ml (8%),95% CI 47.6–182.3,p=0.005). At the end of the study the loss of brain parenchyma correlated significantly with change in EDSS (r= 0.59, p<0.0001). Conclusions—In the early phase of relapsing-remitting multiple sclerosis the cognitive deterioration relies more on the development of brain parenchymal volume atrophy than on the extent of burden of disease in the brain. The loss of brain parenchymal volume underlies the progressive accumulation of physical disability from the initial phase of the disease, which becomes more demonstrable only if studied with longer observation periods. Probably, the main pathological substrate of brain atrophy in the early stage of the disease is early axonal loss, which causes the progression of neurological deficits and the development of cognitive impairment. These data support the debated opinion that disease modifying therapy should be initiated as early as possible

Identification of thyroid tumor cell vulnerabilities through a siRNA-based functional screening

The incidence of thyroid carcinoma is rapidly increasing. Although generally associated with good prognosis, a fraction of thyroid tumors are not cured by standard therapy and progress to aggressive forms for which no effective treatments are currently available. In order to identify novel therapeutic targets for thyroid carcinoma, we focused on the discovery of genes essential for sustaining the oncogenic phenotype of thyroid tumor cells, but not required to the same degree for the viability of normal cells (non-oncogene addiction paradigm). We screened a siRNA oligonucleotide library targeting the human druggable genome in thyroid cancer BCPAP cell line in comparison with immortalized normal human thyrocytes (Nthy-ori 3-1). We identified a panel of hit genes whose silencing interferes with the growth of tumor cells, while sparing that of normal ones. Further analysis of three selected hit genes, namely Cyclin D1, MASTL and COPZ1, showed that they represent common vulnerabilities for thyroid tumor cells, as their inhibition reduced the viability of several thyroid tumor cell lines, regardless the histotype or oncogenic lesion. This work identified non-oncogenes essential for sustaining the phenotype of thyroid tumor cells, but not of normal cells, thus suggesting that they might represent promising targets for new therapeutic strategies

A study of some fundamental physicochemical variables on the morphology of mesoporous silica nanoparticles MCM-41 type

[EN] All variables affecting the morphology of mesoporous silica nanoparticles (MSN) should be carefully analyzed in order to truly tailored design their mesoporous structure according to their final use. Although complete control on MCM-41 synthesis has been already claimed, reproducibility and repeatability of results remain a big issue due to the lack of information reported in literature. Stirring rate, reaction volume, and system configuration (i.e., opened or closed reactor) are three variables that are usually omitted, making the comparison of product characteristics difficult. Specifically, the rate of solvent evaporation is seldom disclosed, and its influence has not been previously analyzed. These variables were systematically studied in this work, and they were proven to have a fundamental impact on final particle morphology. Hence, a high degree of circularity (C = 0.97) and monodispersed particle size distributions were only achieved when a stirring speed of 500 rpm and a reaction scale of 500 mL were used in a partially opened system, for a 2 h reaction at 80 degrees C. Well-shaped spherical mesoporous silica nanoparticles with a diameter of 95 nm, a pore size of 2.8 nm, and a total surface area of 954 m(2) g(-1) were obtained. Final characteristics made this product suitable to be used in biomedicine and nanopharmaceutics, especially for the design of drug delivery systems.This study was funded partially by Departamento Administrativo de Ciencia Tecnología e Innovación–COLCIENCIAS (recipient, Angela A. Beltrán-Osuna); Ministerio de Economía y Competitividad, MINECO, research number MAT2016-76039-C4-1-R (Recipient, José L. Gómez-Ribelles); and Universidad Nacional de Colombia, grant number DIB201010021438 (Recipient, Jairo E. Perilla).Beltrán-Osuna, A.; Gómez Ribelles, JL.; Perilla-Perilla, JE. (2017). A study of some fundamental physicochemical variables on the morphology of mesoporous silica nanoparticles MCM-41 type. Journal of Nanoparticle Research. 19(12):1-14. https://doi.org/10.1007/s11051-017-4077-2S1141912Barrabino A (2011) Synthesis of mesoporous silica particles with control of both pore diameter and particle size. Master Thesis, Chalmers University of Technology, SwedenBastos FS, Lima OA, Filho CR, Fernandes LD (2011) Mesoporous molecular sieve MCM-41 synthesis from fluoride media. Brazilian. J Chem Eng 28:649–658Beck JS, Vartuli JC, Roth WJ, Leonowicz ME, Kresge CT, Schmitt KD, Chu CTW, Olson DH, Sheppard EW, McCullen SB, Higgins JB, Schlenker JL (1992) A new family of mesoporous molecular sieves prepared with liquid crystal templates. J Am Chem Soc 114(27):10834–10843. https://doi.org/10.1021/ja00053a020Beltrán-Osuna AA, Perilla JE (2016) Colloidal and spherical mesoporous silica particles: synthesis and new technologies for delivery applications. J Sol-Gel Sci Technol 77(2):480–496. https://doi.org/10.1007/s10971-015-3874-2Bernardos A, Mondragón L, Aznar E et al (2010) Enzyme-responsive intracellular controlled release using nanometric silica mesoporous supports capped with “saccharides”. ACS Nano 4(11):6353–6368. https://doi.org/10.1021/nn101499dBharti C, Nagaich U, Pal AK, Gulati N (2015) Mesoporous silica nanoparticles in target drug delivery system: a review. Int J Pharm Investig 5(3):124–133. https://doi.org/10.4103/2230-973X.160844Brevet D, Hocine O, Delalande A, Raehm L, Charnay C, Midoux P, Durand JO, Pichon C (2014) Improved gene transfer with histidine-functionalized mesoporous silica nanoparticles. Int J Pharm 471(1-2):197–205. https://doi.org/10.1016/j.ijpharm.2014.05.020Cai Q, Luo Z, Pang W et al (2001) Dilute solution routes to various controllable morphologies of MCM-41 silica with a basic medium. Chem Mater 13(2):258–263. https://doi.org/10.1021/cm990661zChakraborty I, Mascharak PK (2016) Mesoporous silica materials and nanoparticles as carriers for controlled and site-specific delivery of gaseous signaling molecules. Microporous Mesoporous Mater 234:409–419. https://doi.org/10.1016/j.micromeso.2016.07.028Chen L, Zhang Z, Yao X, Chen X, Chen X (2015a) Intracellular pH-operated mechanized mesoporous silica nanoparticles as potential drug carries. Microporous Mesoporous Mater 201:169–175. https://doi.org/10.1016/j.micromeso.2014.09.023Chen X, Yao X, Wang C, Chen L, Chen X (2015b) Mesoporous silica nanoparticles capped with fluorescence-conjugated cyclodextrin for pH-activated controlled drug delivery and imaging. Microporous Mesoporous Mater 217:46–53. https://doi.org/10.1016/j.micromeso.2015.06.012Chen Y, Chen H, Shi J (2013) In vivo bio-safety evaluations and diagnostic / therapeutic applications of chemically designed mesoporous silica nanoparticles. Adv Mater 25(23):3144–3176. https://doi.org/10.1002/adma.201205292Chen Y, Shi X, Han B, Qin H, Li Z, Lu Y, Wang J, Kong Y (2012) The complete control for the nanosize of spherical MCM-41. J Nanosci Nanotechnol 12(9):7239–7249. https://doi.org/10.1166/jnn.2012.6459Cheng Y-J, Zeng X, Cheng D-B, Xu XD, Zhang XZ, Zhuo RX, He F (2016) Functional mesoporous silica nanoparticles (MSNs) for highly controllable drug release and synergistic therapy. Colloids Surfaces B Biointerfaces 145:217–225. https://doi.org/10.1016/j.colsurfb.2016.04.051Crommelin DJA, Florence AT (2013) Towards more effective advanced drug delivery systems. Int J Pharm 454(1):496–511. https://doi.org/10.1016/j.ijpharm.2013.02.020Edler KJ (1997) Synthesis and characterisation of the mesoporous molecular sieve, MCM-41. Doctoral dissertation, The Australian National University, AustraliaGuo Z, Liu X-M, Ma L, Li J, Zhang H, Gao YP, Yuan Y (2013) Effects of particle morphology, pore size and surface coating of mesoporous silica on naproxen dissolution rate enhancement. Colloids Surf B Biointerfaces 101:228–235. https://doi.org/10.1016/j.colsurfb.2012.06.026Han N, Wang Y, Bai J, Liu J, Wang Y, Gao Y, Jiang T, Kang W, Wang S (2016) Facile synthesis of the lipid bilayer coated mesoporous silica nanocomposites and their application in drug delivery. Microporous Mesoporous Mater 219:209–218. https://doi.org/10.1016/j.micromeso.2015.08.006Hu X, Wang Y, Peng B (2014) Chitosan-capped mesoporous silica nanoparticles as pH-responsive nanocarriers for controlled drug release. Chem - An Asian J 9(1):319–327. https://doi.org/10.1002/asia.201301105Huh S, Wiench JW, Yoo J et al (2003) Organic functionalization and morphology control of mesoporous silicas via a co-condensation synthesis method. Chem Mater 15(22):4247–4256. https://doi.org/10.1021/cm0210041Ikari K, Suzuki K, Imai H (2006) Structural control of mesoporous silica nanoparticles in a binary surfactant system. Langmuir 22(2):802–806. https://doi.org/10.1021/la0525527Iliade P, Miletto I, Coluccia S, Berlier G (2012) Functionalization of mesoporous MCM-41 with aminopropyl groups by co-condensation and grafting: a physico-chemical characterization. Res Chem Intermed 38(3-5):785–794. https://doi.org/10.1007/s11164-011-0417-5IUPAC (1985) Reporting physisorption data for gas/solid systems. Pure Appl Chem 57:603–619IUPAC (2014) Compendium of chemical terminology-gold book, 2.3.3. International Union of Pure and Applied ChemistryKhezri K, Roghani-Mamaqani H, Sarsabili M, Sobani M, Mirshafiei-Langari SA (2014) Spherical mesoporous silica nanoparticles/tailor-made polystyrene nanocomposites by in situ reverse atom transfer radical polymerization. Polym Sci Ser B 56(6):909–918. https://doi.org/10.1134/S1560090414660026Kresge CT, Leonowicz ME, Roth WJ, Vartuli JC, Beck JS (1992) Ordered mesoporous molecular sieves synthesized by a liquid-crystal template mechanism. Nature 359(6397):710–712. https://doi.org/10.1038/359710a0Lelong G, Bhattacharyya S, Kline S, Cacciaguerra T, Gonzalez MA, Saboungi ML (2008) Effect of surfactant concentration on the morphology and texture of MCM-41 materials. J Phys Chem C 112(29):10674–10680. https://doi.org/10.1021/jp800898nLv X, Zhang L, Xing F, Lin H (2016) Controlled synthesis of monodispersed mesoporous silica nanoparticles: particle size tuning and formation mechanism investigation. Microporous Mesoporous Mater 225:238–244. https://doi.org/10.1016/j.micromeso.2015.12.024Mamaeva V, Sahlgren C, Lindén M (2013) Mesoporous silica nanoparticles in medicine: recent advances. Adv Drug Deliv Rev 65(5):689–702. https://doi.org/10.1016/j.addr.2012.07.018Manzano M, Aina V, Areán CO, Balas F, Cauda V, Colilla M, Delgado MR, Vallet-Regí M (2008) Studies on MCM-41 mesoporous silica for drug delivery: effect of particle morphology and amine functionalization. Chem Eng J 137(1):30–37. https://doi.org/10.1016/j.cej.2007.07.078Merkus HG (2009) Particle size measurements: fundamentals, practice, quality. Springer Science +Businees Media B.V, The NetherlandsMorishige K, Fujii H, Uga M, Kinukawa D (1997) Capillary critical point of argon, nitrogen, oxygen, ethylene, and carbon dioxide in MCM-41. Langmuir 13(13):3494–3498. https://doi.org/10.1021/la970079ude Padua Oliveira DC, de Barros ALB, Belardi RM et al (2016) Mesoporous silica nanoparticles as a potential vaccine adjuvant against Schistosoma mansoni. J Drug Deliv Sci Technol 35:234–240. https://doi.org/10.1016/j.jddst.2016.07.002Phillips E, Penate-Medina O, Zanzonico PB, Carvajal RD, Mohan P, Ye Y, Humm J, Gonen M, Kalaigian H, Schoder H, Strauss HW, Larson SM, Wiesner U, Bradbury MS (2014) Clinical translation of an ultrasmall inorganic optical-PET imaging nanoparticle probe. Sci Transl Med 6(260):260ra149. https://doi.org/10.1126/scitranslmed.3009524Qu F, Zhu G, Lin H, Zhang W, Sun J, Li S, Qiu S (2006) A controlled release of ibuprofen by systematically tailoring the morphology of mesoporous silica materials. J Solid State Chem 179(7):2027–2035. https://doi.org/10.1016/j.jssc.2006.04.002Rafi AA, Mahkam M, Davaran S, Hamishehkar H (2016) A smart pH-responsive nano-carrier as a drug delivery system: a hybrid system comprised of mesoporous nanosilica MCM-41 (as a nano-container) & a pH-sensitive polymer (as smart reversible gatekeepers): preparation, characterization and in vitro releas. Eur J Pharm Sci 93:64–73. https://doi.org/10.1016/j.ejps.2016.08.005Rouquerol J, Rouquerol F, Llewellyn P, et al (2014) Adsorption by powders and porous solids: principles, methodology and applications. Elsevier Ltd.Selvam P, Bhatia SK, Sonwane CG (2001) Recent advances in processing and characterization of periodic mesoporous MCM-41 silicate molecular sieves. Ind Eng Chem Res 40(15):3237–3261. https://doi.org/10.1021/ie0010666Shi YT, Cheng HY, Geng Y, Nan HM, Chen W, Cai Q, Chen BH, Sun XD, Yao YW, Li HD (2010) The size-controllable synthesis of nanometer-sized mesoporous silica in extremely dilute surfactant solution. Mater Chem Phys 120(1):193–198. https://doi.org/10.1016/j.matchemphys.2009.10.045Shibata H, Chiba Y, Kineri T, Matsumoto M, Nishio K (2010) The effect of heat treatment on the interplanar spacing of the mesostructure during the synthesis of mesoporous MCM-41 silica. Colloids Surfaces A Physicochem Eng Asp 358(1-3):1–5. https://doi.org/10.1016/j.colsurfa.2009.12.020Slowing II, Vivero-Escoto JL, Wu C-W, Lin VSY (2008) Mesoporous silica nanoparticles as controlled release drug delivery and gene transfection carriers. Adv Drug Deliv Rev 60(11):1278–1288. https://doi.org/10.1016/j.addr.2008.03.012Sun R, Wang W, Wen Y, Zhang X (2015) Recent advance on mesoporous silica nanoparticles-based controlled release system: intelligent switches open up. Nano 5(4):2019–2053. https://doi.org/10.3390/nano5042019U.S. Department of Health & Human Services (2015) Cancer Nanotechnology PlanUkmar T, Maver U, Planinšek O, Kaučič V, Gaberšček M, Godec A (2011) Understanding controlled drug release from mesoporous silicates: theory and experiment. J Control Release 155(3):409–417. https://doi.org/10.1016/j.jconrel.2011.06.038Vallet-Regi M, Arcos Navarrete D (2016) Nanoceramics in clinical use, 1st edn. The Royal Society of Chemistry, CambridgeVallet-Regi M, Rámila A, Del Real RP, Pérez-Pariente J (2001) A new property of MCM-41: drug delivery system. Chem Mater 13(2):308–311. https://doi.org/10.1021/cm0011559Varga N, Benko M, Sebok D et al (2015) Mesoporous silica core-shell composite functionalized with polyelectrolytes for drug delivery. Microporous Mesoporous Mater 213:134–141. https://doi.org/10.1016/j.micromeso.2015.02.008Wang Y, Zhao Q, Han N, Bai L, Li J, Liu J, Che E, Hu L, Zhang Q, Jiang T, Wang S (2015) Mesoporous silica nanoparticles in drug delivery and biomedical applications. Nanomed Nanotechnol Biol Med 11(2):313–327. https://doi.org/10.1016/j.nano.2014.09.014Wanyika H, Gatebe E, Kioni P et al (2011) Synthesis and characterization of ordered mesoporous silica nanoparticles with tunable physical properties by varying molar composition of reagents. African J Pharm Pharmacol 5(21):2402–2410. https://doi.org/10.5897/AJPP11.592Wu SH, Mou CY, Lin HP (2013) Synthesis of mesoporous silica nanoparticles. Chem Soc Rev 42(9):3862–3875. https://doi.org/10.1039/c3cs35405aXu X, Lü S, Gao C, Wang X, Bai X, Gao N, Liu M (2015a) Facile preparation of pH-sensitive and self-fluorescent mesoporous silica nanoparticles modified with PAMAM dendrimers for label-free imaging and drug delivery. Chem Eng J 266:171–178. https://doi.org/10.1016/j.cej.2014.12.075Xu X, Lü S, Gao C, Wang X, Bai X, Duan H, Gao N, Feng C, Liu M (2015b) Polymeric micelle-coated mesop orous silica nanoparticle for enhanced fluorescent imaging and pH-responsive drug delivery. Chem Eng J 279:851–860. https://doi.org/10.1016/j.cej.2015.05.085Xu X, Lü S, Gao C, Feng C, Wu C, Bai X, Gao N, Wang Z, Liu M (2016) Self-fluorescent and stimuli-responsive mesoporous silica nanoparticles using a double-role curcumin gatekeeper for drug delivery. Chem Eng J 300:185–192. https://doi.org/10.1016/j.cej.2016.04.087Yang Y, Yu C (2015) Advances in silica based nanoparticles for targeted cancer therapy. Nanomedicine nanotechnology. Biol Med 12(2):317–332. https://doi.org/10.1016/j.nano.2015.10.018Zhang H, Tong C, Sha J, Liu B, Lü C (2015) Fluorescent mesoporous silica nanoparticles functionalized graphene oxide: a facile FRET-based ratiometric probe for Hg2+. Sensors Actuators B Chem 206:181–189. https://doi.org/10.1016/j.snb.2014.09.051Zhou C, Yan C, Zhao J, Wang H, Zhou Q, Luo W (2016) Rapid synthesis of morphology-controlled mesoporous silica nanoparticles from silica fume. J Taiwan Inst Chem Eng 62:307–312. https://doi.org/10.1016/j.jtice.2016.01.03