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  1. Voon SH, Kiew LV, Lee HB, Lim SH, Noordin MI, Kamkaew A, et al.
    Small, 2014 Dec 29;10(24):4993-5013.
    PMID: 25164105 DOI: 10.1002/smll.201401416
    Animal models, particularly rodents, are major translational models for evaluating novel anticancer therapeutics. In this review, different types of nanostructure-based photosensitizers that have advanced into the in vivo evaluation stage for the photodynamic therapy (PDT) of cancer are described. This article focuses on the in vivo efficacies of the nanostructures as delivery agents and as energy transducers for photosensitizers in animal models. These materials are useful in overcoming solubility issues, lack of tumor specificity, and access to tumors deep in healthy tissue. At the end of this article, the opportunities made possible by these multiplexed nanostructure-based systems are summarized, as well as the considerable challenges associated with obtaining regulatory approval for such materials. The following questions are also addressed: (1) Is there a pressing demand for more nanoparticle materials? (2) What is the prognosis for regulatory approval of nanoparticles to be used in the clinic?
  2. Lim JK, Chieh DC, Jalak SA, Toh PY, Yasin NH, Ng BW, et al.
    Small, 2012 Jun 11;8(11):1683-92.
    PMID: 22438107 DOI: 10.1002/smll.201102400
    Magnetic collection of the microalgae Chlorella sp. from culture media facilitated by low-gradient magnetophoretic separation is achieved in real time. A removal efficiency as high as 99% is accomplished by binding of iron oxide nanoparticles (NPs) to microalgal cells in the presence of the cationic polyelectrolyte poly(diallyldimethylammonium chloride) (PDDA) as a binder and subsequently subjecting the mixture to a NdFeB permanent magnet with surface magnetic field ≈6000 G and magnetic field gradient <80 T m(-1) . Surface functionalization of magnetic NPs with PDDA before exposure to Chlorella sp. is proven to be more effective in promoting higher magnetophoretic removal efficiency than the conventional procedure, in which premixing of microalgal cells with binder is carried out before the addition of NPs. Rodlike NPs are a superior candidate for enhancing the magnetophoretic separation compared to spherical NPs due to their stable magnetic moment that originates from shape anisotropy and the tendency to form large NP aggregates. Cell chaining is observed for nanorod-tagged Chlorella sp. which eventually fosters the formation of elongated cell clusters.
  3. Setyawati MI, Kutty RV, Leong DT
    Small, 2016 Oct;12(40):5601-5611.
    PMID: 27571230 DOI: 10.1002/smll.201601669
    Targeted drug delivery is one of the key challenges in cancer nanomedicine. Stoichiometric and spatial control over the antibodies placement on the nanomedicine vehicle holds a pivotal role to overcome this key challenge. Here, a DNA tetrahedral is designed with available conjugation sites on its vertices, allowing to bind one, two, or three cetuximab antibodies per DNA nanostructure. This stoichiometrically definable cetuximab conjugated DNA nanostructure shows enhanced targeting on the breast cancer cells, which results with higher overall killing efficacy of the cancer cells.
  4. Kamei KI, Mashimo Y, Yoshioka M, Tokunaga Y, Fockenberg C, Terada S, et al.
    Small, 2017 05;13(18).
    PMID: 28272774 DOI: 10.1002/smll.201603104
    Cellular microenvironments are generally sophisticated, but crucial for regulating the functions of human pluripotent stem cells (hPSCs). Despite tremendous effort in this field, the correlation between the environmental factors-especially the extracellular matrix and soluble cell factors-and the desired cellular functions remains largely unknown because of the lack of appropriate tools to recapitulate in vivo conditions and/or simultaneously evaluate the interplay of different environment factors. Here, a combinatorial platform is developed with integrated microfluidic channels and nanofibers, associated with a method of high-content single-cell analysis, to study the effects of environmental factors on stem cell phenotype. Particular attention is paid to the dependence of hPSC short-term self-renewal on the density and composition of extracellular matrices and initial cell seeding densities. Thus, this combinatorial approach provides insights into the underlying chemical and physical mechanisms that govern stem cell fate decisions.
  5. Lew TTS, Wong MH, Kwak SY, Sinclair R, Koman VB, Strano MS
    Small, 2018 Nov;14(44):e1802086.
    PMID: 30191658 DOI: 10.1002/smll.201802086
    The ability to control the subcellular localization of nanoparticles within living plants offers unique advantages for targeted biomolecule delivery and enables important applications in plant bioengineering. However, the mechanism of nanoparticle transport past plant biological membranes is poorly understood. Here, a mechanistic study of nanoparticle cellular uptake into plant protoplasts is presented. An experimentally validated mathematical model of lipid exchange envelope penetration mechanism for protoplasts, which predicts that the subcellular distribution of nanoparticles in plant cells is dictated by the particle size and the magnitude of the zeta potential, is advanced. The mechanism is completely generic, describing nanoparticles ranging from quantum dots, gold and silica nanoparticles, nanoceria, and single-walled carbon nanotubes (SWNTs). In addition, the use of imaging flow cytometry to investigate the influence of protoplasts' morphological characteristics on nanoparticle uptake efficiency is demonstrated. Using DNA-wrapped SWNTs as model nanoparticles, it is found that glycerolipids, the predominant lipids in chloroplast membranes, exhibit stronger lipid-nanoparticle interaction than phospholipids, the major constituent in protoplast membrane. This work can guide the rational design of nanoparticles for targeted delivery into specific compartments within plant cells without the use of chemical or mechanical aid, potentially enabling various plant engineering applications.
  6. Tan KH, Lim FS, Toh AZY, Zheng XX, Dee CF, Majlis BY, et al.
    Small, 2018 May;14(20):e1704053.
    PMID: 29665226 DOI: 10.1002/smll.201704053
    Observation of visible light trapping in zinc oxide (ZnO) nanorods (NRs) correlated to the optical and photoelectrochemical properties is reported. In this study, ZnO NR diameter and c-axis length respond primarily at two different regions, UV and visible light, respectively. ZnO NR diameter exhibits UV absorption where large ZnO NR diameter area increases light absorption ability leading to high efficient electron-hole pair separation. On the other hand, ZnO NR c-axis length has a dominant effect in visible light resulting from a multiphoton absorption mechanism due to light reflection and trapping behavior in the free space between adjacent ZnO NRs. Furthermore, oxygen vacancies and defects in ZnO NRs are associated with the broad visible emission band of different energy levels also highlighting the possibility of the multiphoton absorption mechanism. It is demonstrated that the minimum average of ZnO NR c-axis length must satisfy the linear regression model of Z p,min = 6.31d to initiate the multiphoton absorption mechanism under visible light. This work indicates the broadening of absorption spectrum from UV to visible light region by incorporating a controllable diameter and c-axis length on vertically aligned ZnO NRs, which is important in optimizing the design and functionality of electronic devices based on light absorption mechanism.
  7. Li F, Ao M, Pham GH, Sunarso J, Chen Y, Liu J, et al.
    Small, 2020 Apr;16(14):e1906276.
    PMID: 32130789 DOI: 10.1002/smll.201906276
    Direct conversion of syngas to dimethyl ether (DME) through the intermediate of methanol allows more efficient DME production in a simpler reactor design relative to the conventional indirect route. Although Cu/ZnO-based multicomponent catalysts are highly active for methanol synthesis in this process, the sintering issue of Cu during the prolonged reaction generally deteriorates their performance. In this work, Cu/ZnO catalysts in a novel octahedron structure are prepared by a two-step pyrolysis of Zn-doped Cu-BTC metal-organic framework (MOF) in N2 and air. The catalyst CZ-350/A, hybrid of MOF-derived Cu/ZnO sample CZ-350 and γ-Al2 O3 for methanol dehydration, displays the best activity for DME formation (7.74% CO conversion and 70.05% DME selectivity) with the lowest deterioration rate over 40 h continuous reaction. Such performance is superior to its counterpart CZ-CP/A made via the conventional coprecipitation method. This is mainly due to the confinement of Cu nanoparticles within the octahedron matrix hindering their migration and aggregation. Besides, partial reduction of ZnO in the activated CZ-350 prompts the formation of Cu+ -O-Zn, further facilitating the DME production with the highest selectivity compared to literature results. The results clearly indicate that Cu and ZnO distribution in the catalyst architecture plays an important role in DME formation.
  8. Ma C, Yin P, Khan K, Tareen AK, Huang R, Du J, et al.
    Small, 2021 Jan 27.
    PMID: 33502109 DOI: 10.1002/smll.202006891
    In this paper, 2D borophene is synthesized through a liquid-phase exfoliation. The morphology and structure of as-prepared borophene are systemically analyzed, and the Z-scan is used to measure the nonlinear optical properties. It is found that the saturable absorber (SA) properties of borophene make it serve as an excellent broadband optical switch, which is strongly used for mode-locking in near- and mid-infrared laser systems. Ultrastable pulses with durations as short as 792 and 693 fs are successfully delivered at the central wavelengths of 1063 and 1560 nm, respectively. Furthermore, stable pulses at a wavelength of 1878 nm are demonstrated from a thulium mode-locked fiber laser based on the same borophene SA. This research reveals a significant potential for borophene used in lasers helping extending the frontiers of photonic technologies.
  9. Nazarzadeh Zare E, Mudhoo A, Ali Khan M, Otero M, Bundhoo ZMA, Patel M, et al.
    Small, 2021 Aug;17(34):e2007840.
    PMID: 33899324 DOI: 10.1002/smll.202007840
    A noticeable interest and steady rise in research studies reporting the design and assessment of smart adsorbents for sequestering aqueous metal ions and xenobiotics has occurred in the last decade. This motivates compiling and reviewing the characteristics, potentials, and performances of this new adsorbent generation's metal ion and xenobiotics sequestration. Herein, stimuli-responsive adsorbents that respond to its media (as internal triggers; e.g., pH and temperature) or external triggers (e.g., magnetic field and light) are highlighted. Readers are then introduced to selective adsorbents that selectively capture materials of interest. This is followed by a discussion of self-healing and self-cleaning adsorbents. Finally, the review ends with research gaps in material designs.
  10. Yu X, Ng SF, Putri LK, Tan LL, Mohamed AR, Ong WJ
    Small, 2021 12;17(48):e2006851.
    PMID: 33909946 DOI: 10.1002/smll.202006851
    Graphitic carbon nitride (g-C3 N4 ) is a kind of ideal metal-free photocatalysts for artificial photosynthesis. At present, pristine g-C3 N4 suffers from small specific surface area, poor light absorption at longer wavelengths, low charge migration rate, and a high recombination rate of photogenerated electron-hole pairs, which significantly limit its performance. Among a myriad of modification strategies, point-defect engineering, namely tunable vacancies and dopant introduction, is capable of harnessing the superb structural, textural, optical, and electronic properties of g-C3 N4 to acquire an ameliorated photocatalytic activity. In view of the burgeoning development in this pacey field, a timely review on the state-of-the-art advancement of point-defect engineering of g-C3 N4 is of vital significance to advance the solar energy conversion. Particularly, insights into the intriguing roles of point defects, the synthesis, characterizations, and the systematic control of point defects, as well as the versatile application of defective g-C3 N4 -based nanomaterials toward photocatalytic water splitting, carbon dioxide reduction and nitrogen fixation will be presented in detail. Lastly, this review will conclude with a balanced perspective on the technical and scientific hindrances and future prospects. Overall, it is envisioned that this review will open a new frontier to uncover novel functionalities of defective g-C3 N4 -based nanostructures in energy catalysis.
  11. Ukrainskaya V, Rubtsov Y, Pershin D, Podoplelova N, Terekhov S, Yaroshevich I, et al.
    Small, 2021 11;17(45):e2102643.
    PMID: 34605165 DOI: 10.1002/smll.202102643
    Development of CAR-T therapy led to immediate success in the treatment of B cell leukemia. Manufacturing of therapy-competent functional CAR-T cells needs robust protocols for ex vivo/in vitro expansion of modified T-cells. This step is challenging, especially if non-viral low-efficiency delivery protocols are used to generate CAR-T cells. Modern protocols for CAR-T cell expansion are imperfect since non-specific stimulation results in rapid outgrowth of CAR-negative T cells, and removal of feeder cells from mixed cultures necessitates additional purification steps. To develop a specific and improved protocol for CAR-T cell expansion, cell-derived membrane vesicles are taken advantage of, and the simple structural demands of the CAR-antigen interaction. This novel approach is to make antigenic microcytospheres from common cell lines stably expressing surface-bound CAR antigens, and then use them for stimulation and expansion of CAR-T cells. The data presented in this article clearly demonstrate that this protocol produced antigen-specific vesicles with the capacity to induce stronger stimulation, proliferation, and functional activity of CAR-T cells than is possible with existing protocols. It is predicted that this new methodology will significantly advance the ability to obtain improved populations of functional CAR-T cells for therapy.
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