FOCAL POINTS
Welcome to Yang’s Drug and Gene Delivery Laboratory !
Dr. Hu Yang’s Drug and Gene Delivery Laboratory at Missouri S&T is committed to conducting cutting-edge biomedical engineering research through convergence research and interdisciplinary collaborations. The laboratory focuses on developing innovative solutions to facilitate drug and gene delivery, promoting improved patient compliance and contributing to the progress of personalized medicine. By integrating various disciplines, including biology, chemistry, materials science, and engineering, the laboratory fosters a collaborative environment that enables researchers to tackle complex challenges in the biomedical field. Dr. Yang’s laboratory serves as an exemplar of Missouri S&T’s commitment to nurturing interdisciplinary partnerships and promoting groundbreaking research, ultimately positioning the university at the forefront of bioengineering advancements. Dr. Yang’s team concentrates on developing novel targeted pharmaceuticals and theranostics biomaterials for diagnosing and treating various cancers, atherosclerosis, and ocular disorders.
LATEST RESEARCH
Nanoassemblies – Artherosclerosis
We synthesized a reactive oxygen species (ROS)-responsive and size-reducible nanoassemblies, formed by multivalent host-guest interactions between β-cyclodextrins (β-CD)-anchored discoidal recombinant high-density lipoprotein (NP3ST) and hyaluronic acid-ferrocene (HA-Fc) conjugates. The HA-Fc/NP3ST nanoassemblies have extended blood circulation time, specifically accumulate in atherosclerotic plaque mediated by the HA receptors CD44 highly expressed in injured endothelium, rapidly disassemble in response to excess ROS in the intimal and release smaller NP3ST, allowing for further plaque penetration, macrophage-targeted cholesterol efflux and drug delivery. (He J, Zhang W, Zhou X, Xu F, Zou J, Zhang Q, Zhao Y, He H, Yang H, Liu J. Reactive oxygen species (ROS)-responsive size-reducible nanoassemblies for deeper atherosclerotic plaque penetration and enhanced macrophage-targeted drug delivery. Bioactive Materials. 2023 Jan 1;19:115-26.)
BIOMIMETICS – CANCER THERAPHY
Extracted cancer cell membrane carries the antigens of the parent tumor cell. This autologous antigen repertoire presents cancer cell membrane-derived nanoparticles highly immunogenic to the body’s immune system. Cancer cell membrane-derived nanoparticles antigenically recapitulate the parental cancer cells and can be exploited to induce immune response reactive with tumor-associated antigens (TAAs). The use of the cancer cell membrane-derived nanoparticles to deliver immunostimulatory adjuvants facilitates the cross-presentation of tumor antigens by antigen-presenting cells and their costimulation, triggering potent antigen-specific T responses to eliminate established tumors. These nanoparticles can be engineered to carry immunostimulatory signals to facilitate the cross-presentation of TAAs and the induction of potent antitumor immunity. In this study, cancer cell membrane-based vesicles (CCMVs) are prepared from B16 melanoma cells and engineered to deliver the immunological agent polyinosinic:polycytidylic acid (poly-IC). We show that CCMV is preferentially uptaken by bone marrow-derived dendritic cells (BMDCs) as compared to other cell types (macrophages, fibroblasts). The efficient delivery of poly-IC to BMDCs results in enhanced antigen cross-presenting capability of BMDCs and T-cell activation. Additionally, immunization of mice with poly-IC-carrying CCMV elicits a potent antitumor immune response. In conclusion, poly-IC-decorated tumor-derived CCMV may be used as a therapeutic vaccine to potentiate antitumor immunity.(He H, Guo C, Liu W, Chen S, Wang XY, Yang H. Engineering nanostructured pure cancer cell membrane‐derived vesicles as a novel therapeutic cancer vaccine. MedComm–Biomaterials and Applications. 2022 Sep;1(2):e22)
Plant–Nanoparticle interactions in soil ecosystems
To study the plant–NP interactions in soil ecosystems exposed to multiple NPs at the same time.soil-grown lettuce was exposed to different concentrations of silver nanoparticles (AgNPs) alone (0–200 mg/kg) or in combination with 100 mg/kg cerium oxide nanoparticles (CeO2NPs) in a greenhouse study. As expected, the concentrations of AgNPs and CeO2NPs in plant tissues were markedly increased in plant tissues grown in NP-treated soil. Surprisingly, the size of AgNPs in roots was much smaller than those in shoots and in freshly prepared suspensions, suggesting that smaller AgNPs were preferably taken up by plant roots and then aggregated into large NPs in lettuce shoots. CeO2NPs significantly modified the uptake and in planta distribution of AgNPs in lettuce. (Xu L, Wang X, Shi H, Hua B, Burken JG, Ma X, Yang H, Yang JJ. Uptake of Engineered Metallic Nanoparticles in Soil by Lettuce in Single and Binary Nanoparticle Systems. ACS Sustainable Chemistry & Engineering. 2022 Dec 7;10(50):16692-700)
Adenovirus-based cancer immunotherapy
In this work, we describe a “double-punch” strategy by combining dendrimer platform and injectable hydrogel encapsulation for delivery of an adenovirus encoding Flagrp170 (Adv-Flagrp170), which has been shown to effectively mount a cytotoxic T lymphocyte response through enhanced tumor immunogenicity and optimized antigen cross-presentation. We first complexed PAMAM generation 4 (G4) with Adv (G4/Adv) to strengthen its transfection efficiency and then loaded G4/Adv into a biocompatible and injectable supramolecular hydrogel (SH) made of α-cyclodextrin and 4-arm polyethylene glycol via host-guest interaction. When tested in a murine melanoma model, the G4/Adv complex was shown to have improved retention at the tumor site. The presence of SH facilitated the targeted gene expression in tumor-infiltrating leukocytes, including antigen-presenting dendritic cells. (Wang J, Guo C, Wang XY, Yang H. “Double-punch” strategy for delivery of viral immunotherapy with prolonged tumor retention and enhanced transfection efficacy. Journal of Controlled Release. 2021 Jan 10;329:328-36.)
