Dr. Rusiou (Alice) Hsu is a postdoc research fellow in the Department of Chemistry, a group member of Prof. Honjie Dai at Stanford University. She was mentored by Prof. Shang-Hsiu Hu and received her Ph.D. degree in Biomedical engineering and environmental science from National Tsing Hua University. Her research interests include droplet-based microfluidic systems, biomaterials, and she focuses on neuroscience in peripheral nerve and brain repair and continues her study on nerve image at Stanford University now. Dr. Hsu was a high school teacher before her Ph. D studies and loves to share life science with her students as she said: “It is a beautiful thing when career and passion come together.”
Honors & Awards
SPARK Translational Pilot Grant Award, Stanford University (2023)
Bio-X travel Award, Stanford University, USA (2022)
Emerging Scholar Award, Society for Biomaterials (SFB), USA (2022)
Fellowship of Postdoctoral Research. (40,000 USD/year), Ministry of Science and Technology, Taiwan. (2021)
Honor member of the Phi Tau Phi Scholastic Honor Society, Phi Tau Phi Scholastic Honor Society of the Republic of China (2021)
Excellent Dissertation Award (200,000 NTD), Tien-Te Lee Biomaterial Foundation (2020)
International inventor Prize (IIP) (Praised by the president of Taiwan), Taiwan (2020)
16th National innovation Award, Ministry of Economic Affairs, Taiwan (2019)
President Scholarship (4-years), Natioonal Tsing-Hau University (2016)
Doctor of Science, National Tsing Hua University (2021)
Ph. D, National Tsing Hua University, Taiwan, Department of Biomedical Engineering and Environmental Science (2021)
Hongjie Dai, Postdoctoral Faculty Sponsor
Current Research and Scholarly Interests
1. Droplet-based microfluidic technology.
2. Polymer synthesis and hydrogel scaffold for tissue regeneration.
3. Drug controlled- released and Nanocarrier design.
4. NIR II window of images for real-time diagnosis.
Wireless charging-mediated angiogenesis and nerve repair by adaptable microporous hydrogels from conductive building blocks
2022; 13 (1): 5172
Traumatic brain injury causes inflammation and glial scarring that impede brain tissue repair, so stimulating angiogenesis and recovery of brain function remain challenging. Here we present an adaptable conductive microporous hydrogel consisting of gold nanoyarn balls-coated injectable building blocks possessing interconnected pores to improve angiogenesis and recovery of brain function in traumatic brain injury. We show that following minimally invasive implantation, the adaptable hydrogel is able to fill defects with complex shapes and regulate the traumatic brain injury environment in a mouse model. We find that placement of this injectable hydrogel at peri-trauma regions enhances mature brain-derived neurotrophic factor by 180% and improves angiogenesis by 250% in vivo within 2 weeks after electromagnetized stimulation, and that these effects facilitate neuron survival and motor function recovery by 50%. We use blood oxygenation level-dependent functional neuroimaging to reveal the successful restoration of functional brain connectivity in the corticostriatal and corticolimbic circuits.
View details for DOI 10.1038/s41467-022-32912-x
View details for Web of Science ID 000849365000011
View details for PubMedID 36056007
View details for PubMedCentralID PMC9440098
High-precision tumor resection down to few-cell level guided by NIR-IIb molecular fluorescence imaging.
Proceedings of the National Academy of Sciences of the United States of America
2022; 119 (15): e2123111119
SignificanceSurgical removal of tumors has been performed to combat cancer for over a century by surgeons relying on visual inspection and experience to identify margins between malignant and healthy tissues. Herein, we present a rare-earth down-conversion nanoparticle-anti-CD105 conjugate for cancer targeting and a handheld imager capable of concurrent photographic imaging and fluorescence/luminescence imaging. An unprecedented tumor-to-muscle ratio was achieved by near-infrared-IIb (NIR-IIb, 1,500 to 1,700 nm) imaging during surgery, 100 times higher than previous organic dyes for unambiguous determination of tumor margin. The sensitivity/biocompatibility/safety of the probes and instrumentation developed here open a paradigm of imaging-guided surgery at the single-cell level, meeting all major requirements for clinical translation to combat cancer and save human lives.
View details for DOI 10.1073/pnas.2123111119
View details for PubMedID 35380898
Marginative Delivery-Mediated Extracellular Leakiness and T Cell Infiltration in Lung Metastasis by a Biomimetic Nanoraspberry
2021; 21 (3): 1375-1383
T lymphocytes infiltrate the most devastating metastatic tumors for immunotherapy, allowing the potential for tumor metastasis suppression. However, tumor heterogeneity often restricts the infiltration of immune cells and possesses immune privilege that leads to protection from the immune attack, especially for invading metastatic clusters. Here, an exosome-camouflaged nanoraspberry (RB@Exo) doubling as a metastases-targeting agent and T cell-infiltration inducer that delivers an anticancer drug and energy is reported. The RB@Exo integrated an exosome-derived margination effect, and density-mediated nanoparticle-induced extracellular leakiness (nanoEL) exhibited more than a 70% colocalization of the RB@Exo to metastatic tumors in the lung in vivo. The release of cancer cell-cell interactions at the metastasis via nanoEL also elicited the 10-fold infiltration of T lymphocytes. The synergy of the T cell infiltration and photolytic effects transported by the RB@Exo deep into the metastatic tumors effectively inhibited the tumor in 60 days when treated with a single alternating magnetic field (AMF).
View details for DOI 10.1021/acs.nanolett.0c04122
View details for Web of Science ID 000619638600024
View details for PubMedID 33562964
4D printing of stretchable nanocookie@conduit material hosting biocues and magnetoelectric stimulation for neurite sprouting
NPG ASIA MATERIALS
2020; 12 (1)
View details for DOI 10.1038/s41427-020-00244-1
View details for Web of Science ID 000571838900003
Transdermal Composite Microneedle Composed of Mesoporous Iron Oxide Nanoraspberry and PVA for Androgenetic Alopecia Treatment
2020; 12 (6)
The transdermal delivery of therapeutic agents amplifying a local concentration of active molecules have received considerable attention in wide biomedical applications, especially in vaccine development and medical beauty. Unlike oral or subcutaneous injections, this approach can not only avoid the loss of efficacy of oral drugs due to the liver's first-pass effect but also reduce the risk of infection by subcutaneous injection. In this study, a magneto-responsive transdermal composite microneedle (MNs) with a mesoporous iron oxide nanoraspberry (MIO), that can improve the drug delivery efficiency, was fabricated by using a 3D printing-molding method. With loading of Minoxidil (Mx, a medication commonly used to slow the progression of hair loss and speed the process of hair regrowth), MNs can break the barrier of the stratum corneum through the puncture ability, and control the delivery dose for treating androgenetic alopecia (AGA). By 3D printing process, the sizes and morphologies of MNs is able to be, easily, architected. The MIOs were embedded into the tip of MNs which can deliver Mx as well as generate mild heating for hair growth, which is potentially attributed by the expansion of hair follicle and drug penetration. Compared to the mice without any treatments, the hair density of mice exhibited an 800% improvement after being treated by MNs with MF at 10-days post-treatment.
View details for DOI 10.3390/polym12061392
View details for Web of Science ID 000550735500001
View details for PubMedID 32580298
View details for PubMedCentralID PMC7362218
Injectable DNA-architected nanoraspberry depot-mediated on-demand programmable refilling and release drug delivery
2020; 12 (20): 11153-11164
Drug delivery depots boosting a local concentration of therapeutic agents have received great attention in clinical applications due to their low occurrence of side effects and high therapeutic efficacy. However, once the payload is exhausted, the local drug concentration will be lower than the therapeutic window. To address this issue, an injectable double-strand deoxyribonucleic acid (DNA)-architected nanoraspberry depot (DNR-depot) was developed that can refill doxorubicin (Dox, an anticancer drug) from the blood and remotely control drug release on demand. The large porous surface on a uniform nanoraspberry (NR) filled covalently with DNA serves as a Dox sponge-like refilling reservoir, and the NR serves as a magnetic electrical absorber. Via the strong affinity between Dox and DNA molecules, the refilling process of Dox can be achieved on DNR-depot both in vitro and in vivo. Upon high-frequency magnetic field (HFMF) treatment, the remotely triggered release of Dox is actuated by the dissociation of Dox and DNA molecules, facilitating an approximately 800% improvement in drug concentration at the tumor site compared to free Dox injection alone. Furthermore, the cycles of refilling and release can be carried out more than 3 times in vivo within 21 days. The combination of refilling and HFMF-programmable Dox release in tumors via DNR-depot can effectively inhibit tumor growth for 30 days.
View details for DOI 10.1039/d0nr01185a
View details for Web of Science ID 000541868300024
View details for PubMedID 32400827
Adaptable Microporous Hydrogels of Propagating NGF-Gradient by Injectable Building Blocks for Accelerated Axonal Outgrowth
2019; 6 (16): 1900520
Injectable hydrogels in regeneration medicine can potentially mimic hierarchical natural living tissue and fill complexly shaped defects with minimally invasive implantation procedures. To achieve this goal, however, the versatile hydrogels that usually possess the nonporous structure and uncontrollable spatial agent release must overcome the difficulties in low cell-penetrative rates of tissue regeneration. In this study, an adaptable microporous hydrogel (AMH) composed of microsized building blocks with opposite charges serves as an injectable matrix with interconnected pores and propagates gradient growth factor for spontaneous assembly into a complex shape in real time. By embedding gradient concentrations of growth factors into the building blocks, the propagated gradient of the nerve growth factor, integrated to the cell-penetrative connected pores constructed by the building blocks in the nerve conduit, effectively promotes cell migration and induces dramatic bridging effects on peripheral nerve defects, achieving axon outgrowth of up to 4.7 mm and twofold axon fiber intensity in 4 days in vivo. Such AMHs with intrinsic properties of tunable mechanical properties, gradient propagation of biocues and effective induction of cell migration are potentially able to overcome the limitations of hydrogel-mediated tissue regeneration in general and can possibly be used in clinical applications.
View details for DOI 10.1002/advs.201900520
View details for Web of Science ID 000474835300001
View details for PubMedID 31453065
View details for PubMedCentralID PMC6702647
The Penetrated Delivery of Drug and Energy to Tumors by Lipo-Graphene Nanosponges for Photolytic Therapy
2016; 10 (10): 9420-9433
Delivery of drug and energy within responsive carriers that effectively target and accumulate in cancer cells promises to mitigate side effects and to enhance the uniquely therapeutic efficacy demanded for personalized medicine. To achieve this goal, however, these carriers, which are usually piled up at the periphery of tumors near the blood vessel, must simultaneously overcome the challenges associated with low tumor penetration and the transport of sufficient cargos to deep tumors to eradicate whole cancer cells. Here, we report a sponge-like carbon material on graphene nanosheet (graphene nanosponge)-supported lipid bilayers (lipo-GNS) that doubles as a photothermal agent and a high cargo payload platform and releases a burst of drug/energy (docetaxel (DTX) and gasified perfluorohexane (PFH)) and intense heat upon near-infrared irradiation. Ultrasmall lipo-GNS (40 nm) modified with a tumor-targeting protein that penetrates tumor spheroids through transcytosis exhibited a 200-fold increase in accumulation relative to a 270 nm variant of the lipo-GNS. Furthermore, a combination of therapeutic agents (DTX and PFH) delivered by lipo-GNS into tumors was gasified and released into tumor spheroids and successfully ruptured and suppressed xenograft tumors in 16 days without distal harm when subjected to a single 10 min near-infrared laser treatment. Moreover, no tumor recurrence was observed over 60 days post-treatment. This sophisticated lipo-GNS is an excellent delivery platform for penetrated, photoresponsive, and combined gasification/chemo-thermotherapy to facilitate tumor treatment and for use in other biological applications.
View details for DOI 10.1021/acsnano.6b04414
View details for Web of Science ID 000386423600042
View details for PubMedID 27684199
A stepwise mechanism for intercalating hydrophobic organics into multilayered clay nanostructures
2013; 3 (31): 12847-12854
View details for DOI 10.1039/c3ra42037j
View details for Web of Science ID 000321791200047
Mechanism of Silicate Platelet Self-Organization during Clay-Initiated Epoxy Polymerization
JOURNAL OF PHYSICAL CHEMISTRY C
2010; 114 (23): 10373-10378
View details for DOI 10.1021/jp101830a
View details for Web of Science ID 000278479700008
Nanohybrids of Magnetic Iron-Oxide Particles in Hydrophobic Organoclays for Oil Recovery
ACS APPLIED MATERIALS & INTERFACES
2010; 2 (5): 1349-1354
Nanohybrids with magnetic iron-oxide nanoparticles (FeNPs) embedded in the multilayered silicate clay were synthesized by in situ Fe(2+)/Fe(3+) coprecipitation. The natural clay, sodium montmorillonite (Na(+)-MMT), was first modified with hydrophobic poly(oxypropylene)amine salts (POP at 2000 and 4000 g/mol M(w)). The two POP-intercalated organoclays, with a silicate interlayer expansion from 1.2 to 5.2 and 9.2 nm, respectively, are suitable for embedding FeNPs. The presence of POP organics in layered structure created the space for intercalating with FeNPs of 2-4 nm in diameter, observed by transmission electronic microscope. The synthesized nanohybrids of POP4000/MMT-FeNP was composed of 17% iron oxide and 51 wt % POP within the silicate basal spacing of 5.0 nm. In contrast, the lower molecular weight of POP2000 intercalated MMT failed to encapsulate FeNPs in a significant amount, but resulting a "crowding-out effect" that caused the silicate interlayer space to shrink from 5.2 to 1.8 nm because of the replacement of the POP salt by Fe(2+)/Fe(3+) ions. The synthesis required the use of high molecular weight POP4000 and low temperatures (<4 degrees C) for a better dispersion in the reaction medium. The presence of POP in the layered silicate facilitated a homogeneous POP/MMT in water, associating with Fe(2+)/Fe(3+) ions and spatially accommodating for the subsequently generated FeNPs. The synthesized nanostructure consisting of POP and FeNP could be used as a pollutant remedy because of its ability to adsorbing crude oil and it is maneuverable under an applied magnetism.
View details for DOI 10.1021/am100019t
View details for Web of Science ID 000277977400013
View details for PubMedID 20402492
Thermoresponsive Dual-Phase Transition and 3D Self-Assembly of Poly(N-Isopropylacrylamide) Tethered to Silicate Platelets
CHEMISTRY OF MATERIALS
2009; 21 (17): 4071-4079
View details for DOI 10.1021/cm901560e
View details for Web of Science ID 000269485300020
Synthesis of acrylic copolymers consisting of multiple amine pendants for dispersing pigment
JOURNAL OF COLLOID AND INTERFACE SCIENCE
2009; 334 (1): 42-49
A class of acrylic copolymers with narrow molecular weight distribution from butyl methacrylate and glycidyl methacrylate comonomers via atom transfer radical polymerization was synthesized. Various types of polarities including hydroxyl-amines, glycols, and carboxylic acids were then grafted onto the oxirane side groups. The resultant comb-like copolymers with different polar pendants were tested for homogenizing a representative Yellow pigment in 1,6-hexanediol diacrylate medium. Specifically, the polyacrylates with 1,3-diamine pendants (7-10 multiplicity on each polymer strain) enabled to homogeneously disperse the pigment than the analogous copolymers with hydroxyl or carboxylic acid groups. Ultimately, the pigment dispersion with an average size of ca. 20 nm in diameter, high transmittance and low viscosity was achieved. Furthermore, the pigment dispersion was allowed to UV-cure into a film, and for the first time, the primary structures of the pigment particles (ca. 50 nm in diameter) were observed by transmission electronic microscope.
View details for DOI 10.1016/j.jcis.2009.03.069
View details for Web of Science ID 000266303500007
View details for PubMedID 19364609