Professional Education

  • Doctor of Philosophy, McGill University, Chemistry (2019)
  • Bachelor of Science, Korea Advanced Institute of Science and Technology, Chemistry (2014)

All Publications

  • Heat-activated growth of metastable and length-defined DNA fibers expands traditional polymer assembly. Nature communications Dore, M. D., Rafique, M. G., Yang, T. P., Zorman, M., Platnich, C. M., Xu, P., Trinh, T., Rizzuto, F. J., Cosa, G., Li, J., GuarnĂ©, A., Sleiman, H. F. 2024; 15 (1): 4384


    Biopolymers such as nucleic acids and proteins exhibit dynamic backbone folding, wherein site-specific intramolecular interactions determine overall structure. Proteins then hierarchically assemble into supramolecular polymers such as microtubules, that are robust yet dynamic, constantly growing or shortening to adjust to cellular needs. The combination of dynamic, energy-driven folding and growth with structural stiffness and length control is difficult to achieve in synthetic polymer self-assembly. Here we show that highly charged, monodisperse DNA-oligomers assemble via seeded growth into length-controlled supramolecular fibers during heating; when the temperature is lowered, these metastable fibers slowly disassemble. Furthermore, the specific molecular structures of oligomers that promote fiber formation contradict the typical theory of block copolymer self-assembly. Efficient curling and packing of the oligomers - or 'curlamers' - determine morphology, rather than hydrophobic to hydrophilic ratio. Addition of a small molecule stabilises the DNA fibers, enabling temporal control of polymer lifetime and underscoring their potential use in nucleic-acid delivery, stimuli-responsive biomaterials, and soft robotics.

    View details for DOI 10.1038/s41467-024-48722-2

    View details for PubMedID 38782917

    View details for PubMedCentralID PMC11116425

  • Supramolecular Nucleic Acid-Based Organosilica Nanoparticles Responsive to Physical and Biological Inputs. Journal of the American Chemical Society Picchetti, P., Volpi, S., Sancho-Albero, M., Rossetti, M., Dore, M. D., Trinh, T., Biedermann, F., Neri, M., Bertucci, A., Porchetta, A., Corradini, R., Sleiman, H., De Cola, L. 2023


    Organosilica nanoparticles that contain responsive organic building blocks as constitutive components of the silica network offer promising opportunities for the development of innovative drug formulations, biomolecule delivery, and diagnostic tools. However, the synthetic challenges required to introduce dynamic and multifunctional building blocks have hindered the realization of biomimicking nanoparticles. In this study, capitalizing on our previous research on responsive nucleic acid-based organosilica nanoparticles, we combine the supramolecular programmability of nucleic acid (NA) interactions with sol-gel chemistry. This approach allows us to create dynamic supramolecular bridging units of nucleic acids in a silica-based scaffold. Two peptide nucleic acid-based monoalkoxysilane derivatives, which self-assemble into a supramolecular bis-alkoxysilane through direct base pairing, were chosen as the noncovalent units inserted into the silica network. In addition, a bridging functional NA aptamer leads to the specific recognition of ATP molecules. In a one-step bottom-up approach, the resulting supramolecular building blocks can be used to prepare responsive organosilica nanoparticles. The supramolecular Watson-Crick-Franklin interactions of the organosilica nanoparticles result in a programmable response to external physical (i.e., temperature) and biological (i.e., DNA and ATP) inputs and thus pave the way for the rational design of multifunctional silica materials with application from drug delivery to theranostics.

    View details for DOI 10.1021/jacs.3c04345

    View details for PubMedID 37844092

  • Responsive Nucleic Acid-Based Organosilica Nanoparticles. Journal of the American Chemical Society Picchetti, P., Volpi, S., Rossetti, M., Dore, M. D., Trinh, T., Biedermann, F., Neri, M., Bertucci, A., Porchetta, A., Corradini, R., Sleiman, H., De Cola, L. 2023


    The development of smart nanoparticles (NPs) that encode responsive features in the structural framework promises to extend the applications of NP-based drugs, vaccines, and diagnostic tools. New nanocarriers would ideally consist of a minimal number of biocompatible components and exhibit multiresponsive behavior to specific biomolecules, but progress is limited by the difficulty of synthesizing suitable building blocks. Through a nature-inspired approach that combines the programmability of nucleic acid interactions and sol-gel chemistry, we report the incorporation of synthetic nucleic acids and analogs, as constitutive components, into organosilica NPs. We prepared different nanomaterials containing single-stranded nucleic acids that are covalently embedded in the silica network. Through the incorporation of functional nucleic acids into the organosilica framework, the particles respond to various biological, physical, and chemical inputs, resulting in detectable physicochemical changes. The one-step bottom-up approach used to prepare organosilica NPs provides multifunctional systems that combine the tunability of oligonucleotides with the stiffness, low cost, and biocompatibility of silica for different applications ranging from drug delivery to sensing.

    View details for DOI 10.1021/jacs.3c00393

    View details for PubMedID 37734737

  • A Photoresponsive Intramolecular Triplex Motif That Enables Rapid and Reversible Control of Aptamer Binding Activity. ACS nano Trinh, T., Thompson, I. A., Clark, F., Remington, J. M., Eisenstein, M., Li, J., Soh, H. T. 2022


    DNA switches that can change conformation in response to certain wavelengths of light could enable rapid and noninvasive control of chemical processes for a wide range of applications. However, most current photoresponsive DNA switches are limited by either irreversible switching or reversible switching with impractically slow kinetics. Here, we report the design of an intramolecular triplex photoswitch (TPS) design based on single-stranded DNA that undergoes rapid and reversible photoswitching between folded and unfolded states through isomerization of internal azobenzene modifications. After optimizing the performance of our photoswitch design, we used molecular dynamics simulations to reveal how individual azobenzenes contribute to the stabilization or destabilization of the triplex depending on their photoisomerization state. By coupling our TPS to an existing aptamer, we can reversibly modulate its binding affinity with less than 15 s of UV light exposure. We further demonstrate reproducible shifting in affinity over multiple cycles of UV and blue light irradiation without substantial photobleaching.

    View details for DOI 10.1021/acsnano.2c05010

    View details for PubMedID 36094303

  • Asymmetric patterning drives the folding of a tripodal DNA nanotweezer CHEMICAL SCIENCE Saliba, D., Trinh, T., Lachance-Brais, C., Prinzen, A. L., Rizzuto, F. J., de Rochambeau, D., Sleiman, H. F. 2021; 13 (1): 74-80


    DNA tweezers have emerged as powerful devices for a wide range of biochemical and sensing applications; however, most DNA tweezers consist of single units activated by DNA recognition, limiting their range of motion and ability to respond to complex stimuli. Herein, we present an extended, tripodal DNA nanotweezer with a small molecule junction. Simultaneous, asymmetric elongation of our molecular core is achieved using polymerase chain reaction (PCR) to produce length- and sequence-specific DNA arms with repeating DNA regions. When rigidified, our DNA tweezer can be addressed with streptavidin-binding ligands. Full control over the number, separation, and location of these ligands enables site-specific streptavidin recognition; all three arms of the DNA nanotweezer wrap around multiple streptavidin units simultaneously. Our approach combines the simplicity of DNA tile arrays with the size regime normally provided by DNA origami, offering an integrated platform for the use of branched DNA scaffolds as structural building blocks, protein sensors, and dynamic, stimuli-responsive materials.

    View details for DOI 10.1039/d1sc04793k

    View details for Web of Science ID 000728939800001

    View details for PubMedID 35059153

    View details for PubMedCentralID PMC8694393

  • Thermosetting supramolecular polymerization of compartmentalized DNA fibers with stereo sequence and length control CHEM Dore, M. D., Trinh, T., Zorman, M., de Rochambeau, D., Platnich, C. M., Xu, P., Luo, X., Remington, J. M., Toader, V., Cosa, G., Li, J., Sleiman, H. F. 2021; 7 (9): 2395-2414
  • Amplified Self-Immolative Release of Small Molecules by Spatial Isolation of Reactive Groups on DNA-Minimal Architectures ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Prinzen, A. L., Saliba, D., Hennecker, C., Trinh, T., Mittermaier, A., Sleiman, H. F. 2020; 59 (31): 12900-12908


    Triggering the release of small molecules in response to unique biomarkers is important for applications in drug delivery and biodetection. Due to low quantities of biomarker, amplifying release is necessary to gain appreciable responses. Nucleic acids have been used for both their biomarker-recognition properties and as stimuli, notably in amplified small-molecule release by nucleic-acid-templated catalysis (NATC). The multiple components and reversibility of NATC, however, make it difficult to apply in vivo. Herein, we report the use of the hybridization chain reaction (HCR) for the amplified, conditional release of small molecules from standalone nanodevices. We couple HCR with a DNA-templated reaction resulting in the amplified, immolative release of small molecules. We integrate the HCR components into single nanodevices as DNA tracks and spherical nucleic acids, spatially isolating reactive groups until triggering. This could be applied to biosensing, imaging, and drug delivery.

    View details for DOI 10.1002/anie.202001123

    View details for Web of Science ID 000535268900001

    View details for PubMedID 32277788

  • "Printing" DNA Strand Patterns on Small Molecules with Control of Valency, Directionality, and Sequence ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Trinh, T., Saliba, D., Liao, C., de Rochambeau, D., Prinzen, A., Li, J., Sleiman, H. F. 2019; 58 (10): 3042-3047


    The incorporation of synthetic molecules as corner units in DNA structures has been of interest over the last two decades. In this work, we present a facile method for generating branched small molecule-DNA hybrids with controllable valency, different sequences, and directionalities (5'-3') using a "printing" process from a simple 3-way junction structure. We also show that the DNA-imprinted small molecule can be extended asymmetrically using polymerase chain reaction (PCR) and can be replicated chemically. This strategy provides opportunities to achieve new structural motifs in DNA nanotechnology and introduce new functionalities to DNA nanostructures.

    View details for DOI 10.1002/anie.201809251

    View details for Web of Science ID 000459709300012

    View details for PubMedID 30290048

  • DNA Nanotubes with Hydrophobic Environments: Toward New Platforms for Guest Encapsulation and Cellular Delivery ADVANCED HEALTHCARE MATERIALS Rahbani, J. F., Vengut-Climent, E., Chidchob, P., Gidi, Y., Tuan Trinh, Cosa, G., Sleiman, H. F. 2018; 7 (6): e1701049


    Natural systems combine different supramolecular interactions in a hierarchical manner to build structures. In contrast, DNA nanotechnology relies almost exclusively on DNA base pairing for structure generation. Introducing other supramolecular interactions can expand the structural and functional range of DNA assemblies, but this requires an understanding of the interplay between these interactions. Here, an economic strategy to build DNA nanotubes functionalized with lipid-like polymers is reported. When these polymers are linked to the nanotube using a spacer, they fold inside to create a hydrophobic environment within the nanotube; the nanotube can encapsulate small molecules and conditionally release them when specific DNA strands are added, as monitored by single-molecule fluorescence microscopy. When the polymers are directly linked to the nanostructure without spacers, they interact intermolecularly to form a network of DNA bundles. This morphological switch can be directly observed using a strand displacement strategy. The two association modes result in different cellular uptake behavior. Nanotubes with internal hydrophobic association show dye-mediated mitochondrial colocalization inside cells; while the bundles disassemble into smaller polymer-coated structures that reduce the extent of nonspecific cellular uptake. This approach uncovers parameters to direct the hierarchical assembly of DNA nanostructures, and produces promising materials for targeted drug delivery.

    View details for DOI 10.1002/adhm.201701049

    View details for Web of Science ID 000428311900012

    View details for PubMedID 29356412

  • DNA-imprinted polymer nanoparticles with monodispersity and prescribed DNA-strand patterns NATURE CHEMISTRY Tuan Trinh, Liao, C., Toader, V., Barlog, M., Bazzi, H. S., Li, J., Sleiman, H. F. 2018; 10 (2): 184-192


    As colloidal self-assembly increasingly approaches the complexity of natural systems, an ongoing challenge is to generate non-centrosymmetric structures. For example, patchy, Janus or living crystallization particles have significantly advanced the area of polymer assembly. It has remained difficult, however, to devise polymer particles that associate in a directional manner, with controlled valency and recognition motifs. Here, we present a method to transfer DNA patterns from a DNA cage to a polymeric nanoparticle encapsulated inside the cage in three dimensions. The resulting DNA-imprinted particles (DIPs), which are 'moulded' on the inside of the DNA cage, consist of a monodisperse crosslinked polymer core with a predetermined pattern of different DNA strands covalently 'printed' on their exterior, and further assemble with programmability and directionality. The number, orientation and sequence of DNA strands grafted onto the polymeric core can be controlled during the process, and the strands are addressable independently of each other.

    View details for DOI 10.1038/NCHEM.2893

    View details for Web of Science ID 000423144000014

    View details for PubMedID 29359762

  • Light-induced picosecond rotational disordering of the inorganic sublattice in hybrid perovskites. Science advances Wu, X. n., Tan, L. Z., Shen, X. n., Hu, T. n., Miyata, K. n., Trinh, M. T., Li, R. n., Coffee, R. n., Liu, S. n., Egger, D. A., Makasyuk, I. n., Zheng, Q. n., Fry, A. n., Robinson, J. S., Smith, M. D., Guzelturk, B. n., Karunadasa, H. I., Wang, X. n., Zhu, X. n., Kronik, L. n., Rappe, A. M., Lindenberg, A. M. 2017; 3 (7): e1602388


    Femtosecond resolution electron scattering techniques are applied to resolve the first atomic-scale steps following absorption of a photon in the prototypical hybrid perovskite methylammonium lead iodide. Following above-gap photoexcitation, we directly resolve the transfer of energy from hot carriers to the lattice by recording changes in the mean square atomic displacements on 10-ps time scales. Measurements of the time-dependent pair distribution function show an unexpected broadening of the iodine-iodine correlation function while preserving the Pb-I distance. This indicates the formation of a rotationally disordered halide octahedral structure developing on picosecond time scales. This work shows the important role of light-induced structural deformations within the inorganic sublattice in elucidating the unique optoelectronic functionality exhibited by hybrid perovskites and provides new understanding of hot carrier-lattice interactions, which fundamentally determine solar cell efficiencies.

    View details for PubMedID 28782016

  • DNA micelles as nanoreactors: efficient DNA functionalization with hydrophobic organic molecules CHEMICAL COMMUNICATIONS Trinh, T., Chidchob, P., Bazzi, H. S., Sleiman, H. F. 2016; 52 (72): 10914-10917


    We report a micelle-templated method to enhance the reactivity of DNA with highly hydrophobic molecules. Lipids, chromophores and polymers can be conjugated to DNA in high yield and under mild conditions. This method expands the range of DNA-templated reactions for DNA-encoded libraries, oligonucleotide and drug delivery, nanopore mimetics and DNA nanotechnology.

    View details for DOI 10.1039/c6cc04970b

    View details for Web of Science ID 000382673600023

    View details for PubMedID 27533528

  • Antisense precision polymer micelles require less poly(ethylenimine) for efficient gene knockdown (vol 7, pg 20625, 2015) NANOSCALE Fakhoury, J. J., Edwardson, T. G., Conway, J. W., Trinh, T., Khan, F., Barlog, M., Bazzi, H. S., Sleiman, H. F. 2016; 8 (19): 10453


    Correction for 'Antisense precision polymer micelles require less poly(ethylenimine) for efficient gene knockdown' by Johans J. Fakhoury, et al., Nanoscale, 2015, 7, 20625-20634.

    View details for DOI 10.1039/c6nr90089e

    View details for Web of Science ID 000376047200061

    View details for PubMedID 27126130

  • Antisense precision polymer micelles require less poly(ethylenimine) for efficient gene knockdown NANOSCALE Fakhoury, J. J., Edwardson, T. G., Conway, J. W., Tuan Trinh, Khan, F., Barlog, M., Bazzi, H. S., Sleiman, H. F. 2015; 7 (48): 20625-20634


    Therapeutic nucleic acids are powerful molecules for shutting down protein expression. However, their cellular uptake is poor and requires transport vectors, such as cationic polymers. Of these, poly(ethylenimine) (PEI) has been shown to be an efficient vehicle for nucleic acid transport into cells. However, cytotoxicity has been a major hurdle in the development of PEI-DNA complexes as clinically viable therapeutics. We have synthesized antisense-polymer conjugates, where the polymeric block is completely monodisperse and sequence-controlled. Depending on the polymer sequence, these can self-assemble to produce micelles of very low polydispersity. The introduction of linear poly(ethylenimine) to these micelles leads to aggregation into size-defined PEI-mediated superstructures. Subsequently, both cellular uptake and gene silencing are greatly enhanced over extended periods compared to antisense alone, while at the same time cellular cytotoxicity remains very low. In contrast, gene silencing is not enhanced with antisense polymer conjugates that are not able to self-assemble into micelles. Thus, using antisense precision micelles, we are able to achieve significant transfection and knockdown with minimal cytotoxicity at much lower concentrations of linear PEI then previously reported. Consequently, a conceptual solution to the problem of antisense or siRNA delivery is to self-assemble these molecules into 'gene-like' micelles with high local charge and increased stability, thus reducing the amount of transfection agent needed for effective gene silencing.

    View details for DOI 10.1039/c5nr05157f

    View details for Web of Science ID 000365982700034

    View details for PubMedID 26597764