Author: admin

Developing two-dimensional nano-adjuvant for improving immunogenicity of HIV vaccine

Yekkuni L. BALACHANDRAN | 22/12/2021

 

Controlling the spread of the human immunodeficiency (HIV) virus might be the only feasible route for completely avoiding the intractable disease. However, crucial immunities are still difficult to be sufficiently triggered by vaccines alone, which greatly limits its practical application.

Researchers from the Microfluidic-Biomaterials Lab at the Southern University of Science and Technology (SUSTech) have developed a two-dimensional nano-adjuvant comprising of rare-earth elements that improve the immunities generated by vaccines (HIV DNA vaccine in this case).

The research article, titled “Two-dimensional nanosheets as immunoregulator improve HIV vaccine efficacy,” was published in Chemical Sciences, a scientific journal covering all aspects of chemistry.

Introducing applicable immunoregulatory building blocks to endow planar materials with inherent immunoregulatory characteristics is a strenuous task. Some rare earths or rare-earth based complexes, because of their inherent immunoregulatory capability, can regulate the behavior of macrophages (antigen-representing cells) and immunity. Considering that multiple types of rare earths have immunoregulatory effects on the functions or behaviors of immune effector cells, selecting rare earths rationally is a core question for the design of immunoregulatory nanomaterials.

Two rare earths, erbium (Er) and dysprosium (Dy), can activate macrophages and improve phagocytosis capability and bioactivity for the increased presentation of antigens. The heterogeneity of two-dimensional nanosheets (2D NSs) comprehensively regulates immune functions of both Er (ROS-based mechanism) and Dy (NO-based mechanism), in comparison with either Er- or Dy-alone 2D NSs.

Because of their planar morphology, these 2D NSs target the mice lymph nodes without the use of any lymph node targeting functional molecules. Considering lymph nodes are a critical type of immunological tissue for mediating immune responses, the lymph node targeting capability of nanosheets effectively improve the efficacy of vaccines.

Figure 1. Characterization of rare-earth 2D NSs.

In regulating DNA vaccine-triggered immune responses, the 2D NSs simultaneously improve both humoral and cellular immune responses, compared to most other reported immunoregulators, which can only enhance either humoral or cellular responses. 2D NSs significantly improve the HIV-specific humoral response of IgG and the four subclasses (IgG1, IgG2a, IgG2b, and IgG3).

Furthermore, the 2D NSs can boost the enhancement of cytotoxic T lymphocytes to produce HIV-specific IFN-γ to neutralize HIV-infected cells. The balanced enhancement of HIV-specific humoral and cellular immune responses regulated by 2D NSs gives an unparalleled advantage for realizing the neutralization (mediated by humoral response) and cytotoxicity (cellular response) against HIV.

Figure 2. 2D NSs regulating HIV DNA vaccine-triggered immune responses

2D NSs-regulated HIV vaccine triggers six critical genes associated with various immunoregulation-related networks. The three natural killer cell lectin-like receptor subfamily genes Klrk1, Klrd1, and Klrc1, are triggered by nanosheets, which can effectively enhance the presentation of antigens. The 2D NSs induce the upregulation of the genes Ccr2 and Serpinb9 to regulate cytokine production. The 2D NSs are found to significantly up-regulate the expression of Msr1, a critical gene that activates the macrophages. The 2D NSs influences the immunoregulation-related network involving the activation of immune cells, antigen presentation, and the production of immune effectors to facilitate the HIV DNA vaccine to trigger stronger immune responses.

Figure 3. Transcriptome profiling of 2D NSs improving HIV DNA vaccine

In summary, the realization of the concept of 2D NSs immunoregulator dramatically broadens the choices to optimize the vaccination of infectious diseases, tumor immunotherapy, and other immune-based preventive treatment and therapy.

The Microfluidic-Biomaterials Lab at SUSTech is the corresponding author of this paper.

This work was supported by the National Natural Science Foundation of China (NSFC), the National Key R&D Program of China, the Chinese Academy of Sciences, Tencent Foundation through the XPLORER PRIZE, the Shenzhen Key Laboratory of Smart Healthcare Engineering, the Leading Medical Talents Program of Health Commission of Yunnan Province, the Young and Middle-Aged Academic and Technical Leaders Program of Yunnan Province, and the Basic Research Program of Yunnan Province.

Paper link: https://pubs.rsc.org/en/content/articlelanding/2022/SC/D1SC04044H 

Scholars from Microfluidic-Biomaterials Lab at SUSTech win Cell Press award

Recently, scientists of the Microfluidic-Biomaterials Lab at the Southern University of Science and Technology (SUSTech) received the Chinese Scientists with Cell Press Best Paper Award 2020.

Their paper, titled “Electronic Blood Vessel,” was published in Matter, a journal under the Cell Press publishing organization that covers the field of materials science.

The team from SUSTech developed an electronic blood vessel by using poly(L-lactide-co-ε-caprolactone) (PLC) which encapsulates liquid metal to make a flexible and biodegradable circuit.

The electronic blood vessels could integrate flexible electrons with three layers of blood vessel cells to imitate and surpass natural blood vessels. It can effectively promote cell proliferation and migration in the wound healing model through electrical stimulation. It can controllably deliver genes to specific parts of the blood vessel through electro-transfection.

Through a 3-month in vivo study of the rabbit carotid artery replacement model, the authors evaluated the electronic blood vessel’s efficacy and biological safety in the vascular system. They confirmed its patency through ultrasound imaging and angiography.

The research paves the way for the integration of flexible, degradable bioelectronics into the vascular system, which can be used as a platform for further treatments, such as gene therapy, electrical stimulation, and electronically controlled drug release.

In the future, the electronic blood vessel can be integrated with other electronic components and devices to achieve diagnostic and therapeutic functions. This will enhance significantly personalized medical functions by establishing a direct connection in the blood vessel tissue-machine interface.

Cell Press is an internationally renowned academic publishing organization. Since 2015, it has looked at Chinese papers published in its journals and promotes the scientific research achievements of Chinese scientists in life sciences, materials science, and interdisciplinary science.

Paper link: https://www.sciencedirect.com/science/article/pii/S2590238520304938

SUSTech Changfeng Wu’s group develops highly bright polymer dots for three-dimensional multicolor super-resolution imaging applications

Recently, a research team led by Professor Changfeng Wu from the Department of Biomedical Engineering at the Southern University of Science and Technology (SUSTech) developed a series of highly bright polymer dots probes. Through the functionalization of polymer dots probes and application in expansion microscopy, fine subcellular structures with a resolution of ≈ 30 nm can be resolved on a conventional fluorescent microscope. Their research, entitled “Expansion Microscopy with Multifunctional Polymer Dots,” was published in Advanced Materials, a top journal in the field of materials science.

 

 

Super-resolution optical imaging won the 2014 Nobel Prize in Chemistry for its ability to provide resolution below the diffraction limit. The current super-resolution technology mainly contains two categories, one of which relies on patterned illumination modulation and the other one based on single-molecule positioning. Expansion microscopy uses a completely different strategy that physically enlarges the samples to allow clear distinction of adjacent molecules that are originally within the diffraction limit. This method does not rely on a complex imaging system, and nanoscale resolution can be achieved on a common confocal microscope. However, the fluorescence brightness attenuation caused by chemical quenching and density dilution during sample preparation has long been a challenge for further applications.   

 

Changfeng Wu’s research group developed multifunctional polymer dots for application in multicolor expansion microscopy to address this issue. The fluorescence intensity of Pdots in ExM was up to 6 times higher than those achieved using commercially available Alexa dyes. The impressive brightness of the Pdots facilitated multicolor ExM, thereby enabling a variety of subcellular structures, such as mitochondria, clathrin-coated pits, and neuron synapses to be visualized on traditional fluorescent microscopes (Figure 1a-c). Furthermore, the research group combined polymer dots probes, expansion microscopy, and super-resolution optical fluctuation microscopy to achieve ultrahigh-resolution imaging of subcellular structures on a conventional wide-field microscope. As a result, this reflected the actual size of microtubules and the hollow membrane structure of mitochondria (Figure 1d-j). These findings highlight the immense potential of highly bright polymer dots for biological imaging.

Figure 1. Three-dimensional super-resolution expansion and optical fluctuation imaging of subcellular structures

 

The immunofluorescence staining of samples is tedious and time-consuming. To improve the efficiency of the project, Zhihe Liu, a postdoctoral fellow in the research group, designed an automatic cell immunostaining system (Figure 2). As a result, this could replace manual work for immunofluorescence staining experiments.

Figure 2. Automatic cell immunostaining system

 

Jie Liu, a doctoral student supported by the joint Ph.D. program between SUSTech and the Hong Kong Baptist University (HKBU), is the first author of this paper. SUSTech is the correspondence unit of this paper. The above research has been supported by the National Natural Science Foundation of China (NSFC), the National Key R&D Program of China, and the Shenzhen Science and Technology Innovation Commission. 

 

Paper link: https://doi.org/10.1002/adma.202007854

Department of Biomedical Engineering holds 5th Anniversary Achievement Exhibition

On May 22, 2021, the Department of Biomedical Engineering (BME) at the Southern University of Science and Technology (SUSTech) celebrated its 5th anniversary by holding an Achievement Exhibition.

The achievement exhibition was made accessible for both online and offline participation. Yusheng ZHAO, Acting Vice President of SUSTech and Dean of the SUSTech Academy for Advanced Interdisciplinary Studies, attended the event.

 

 

Yusheng ZHAO said that BME has developed rapidly in the past five years and has achieved remarkable results. He hopes that the department will continue to strengthen and grow in the future while also promoting the cross-integration of disciplines and innovation of advanced technology.  

Xingyu JIANG, Head of BME, expressed his gratitude to everyone who has helped and supported the development of BME over the past few years. He added that its success wouldn’t have been possible without the support of the leadership team at SUSTech, faculty members, students, and other volunteers that have assisted the department since its formation.

All 17 research groups of BME participated in the exhibition, attracting more than 100 experts, scholars, faculty members, and students within SUSTech to participate in the event.

SUSTech Kai Li’s team makes progress in type-I photosensitizers with tumor-associated macrophages polarizing activity

Recently, Kai Li’s laboratory at the Department of Biomedical Engineering of the Southern University of Science and Technology (SUSTech) has made significant experimental progress in tumor photodynamic immunotherapy. The research paper, titled “Acceptor Engineering for Optimized ROS Generation Facilitates Reprogramming Macrophages to M1 Phenotype in Photodynamic Immunotherapy” was published by Angewandte Chemie International Edition.

Reprogramming tumor‐associated macrophage cells by photodynamic therapy (PDT) is a promising approach to overcoming the suppression of tumor microenvironment for boosted immunotherapy. It remains unclear how the reactive oxygen species (ROS) generated from type I and II mechanisms relate to the macrophage polarization efficacy. Prof. Li’s team designed and synthesized three photosensitizers with varied ROS‐generating effectiveness.

Surprisingly, they discovered that the extracellular ROS generated from type I mechanisms are mainly responsible for reprogramming the macrophages from a pro‐tumor type (M2) to an anti‐tumor state (M1). In vivo experiments prove that the photosensitizer can produce effective suppression of the tumor growth, while the therapeutic outcome is eliminated with depleted macrophages. Overall, their strategy highlights the design guideline of macrophage‐activated photosensitizers.

Here were the key findings from their analysis:

1. Three donor-acceptor (D-A) structured AIEgen photosensitizers have been synthesized using the compound triphenylamine as the electron donor, and their ROS-generating efficiencies are adjusted by using acceptor units with varied electron deficiencies.

2. Using commercial photosensitizers, such as chlorin 6 (Ce6) and rose bengal (RB), they discover that the extracellular ROS generated from type I mechanism rather than type II mechanism plays a key role in reprogramming the macrophages to M1 phenotype. This is of high importance in in vivo anti-tumor applications, taking into account the lower oxygen dependence of type I PDT mechanism and the hypoxic tumor microenvironment.

3. In vivo results suggest that the tTDCR nanoparticles can lead to a complete removal of a tumor in mice without any relapse, upon a single PDT treatment in the absence of any immune checkpoint inhibitor or immunoadjuvant. This would appear to be attributed to its excellent performance in the activating macrophages. 

Dr. Guang Yang, a post-doctoral at SUSTech, is the first author of this paper. Prof. Kai Li, also of SUSTech, is the corresponding author. Jen-Shyang Ni, Yaxi Li, Menglei Zha, and Yao Tu are the co-authors of the paper.

This research was financially supported by the National Natural Science Foundation of China (NSFC), Ministry of Science and Technology of China (MOST), Guangdong Science and Technology Department, and the Shenzhen Science and Technology Program.

Paper Link: https://onlinelibrary.wiley.com/doi/10.1002/anie.202013228

Piconewton-force Dots created for Nanoscale Biomechanics Measurement

Optical tweezers are widely used in materials assembly, characterization, biomechanical force sensing, and the in vivo manipulation of cells and organs. The trapping force has primarily been generated through the refractive index mismatch between a trapped object and its surrounding medium. This poses a fundamental challenge for the optical trapping of low-refractive-index nanoscale objects, including nanoparticles and intracellular organelles.

Prof. Dayong Jin, Chair Professor at SUSTech Department of Biomedical Engineering (BME) and Distinguished Professor at the University of Technology Sydney (UTS), was part of an international collaborative research team that published an article on February 18, 2021, in Nature Nanotechnology, titled as “Optical tweezers beyond refractive index mismatch using highly doped upconversion nanoparticles.”

The research focuses on a technology that employs a resonance effect to enhance the permittivity and polarizability of nanocrystals, leading to enhanced optical trapping forces by orders of magnitude. This effectively bypasses the requirement of refractive index mismatch at the nanoscale.

Figure 1. Comparison between optical trapping of low refractive index nanoparticles with or without doping by lanthanide ions

The study shows that under resonance conditions, highly doping lanthanide ions in NaYF4 nanocrystals makes the real part of the Clausius–Mossotti factor approach its asymptotic limit, thereby achieving a maximum optical trap stiffness of 0.086 pN μm–1 mW–1 for 23.3-nm-radius low-refractive-index (1.46) nanoparticles, that is, more than 30 times stronger than the reported value for gold nanoparticles of the same size.

Figure 2. Escape velocity measurements to quantify the trap stiffness for HeLa cells with and without lanthanide-doped nanoparticles.

In conclusion, this study discovered that highly doping lanthanide ions in single nanoparticles can generate a strong oscillation resonance effect in the electromagnetic field and thereby substantially enhance the optical trapping force. This strategy can bypass the limitation set by the refractive index mismatch between an object and its surrounding medium, suggesting a new way to design far-field optical tweezers on the nanoscale. Also, benefiting from the limited heat generation, compared with gold nanoparticles, this work opens the door to a highly efficient, long-term, optical manipulation of biological samples. Furthermore, lanthanide-doped nanoparticles can be designed to be responsive to the surrounding temperature and pH values, and to enable multimodal manipulation.

Mr. Xuchen Shan from the UTS Institute for Biomedical Materials & Devices (IBMD) was the lead author of the paper. Dr. Fan Wang of UTS, Dr. Peter J. Reece of the University of New South Wales (UNSW Sydney), and Prof. Dayong Jin of SUSTech and UTS, are the corresponding authors.

The scholars acknowledge financial support from a UTS Chancellor’s Postdoctoral Research Fellowship, Australian Research Council (ARC) DECRA fellowship, the ARC Discovery Project, the National Natural Science Foundation of China (NSFC), Science and Technology Innovation Commission of Shenzhen, and the Australia–China Science and Research Fund Joint Research Centre for Point-of-Care Testing.

Paper link: https://www.nature.com/articles/s41565-021-00852-0