City University of Seattle

Scientists have achieved a significant breakthrough by inventing a new class of near-infrared-activated photo-oxidants that can effectively kill cancer cells without requiring oxygen. The photo-oxidants induce a unique form of cancer cell death that can overcome cancer cell resistance. The findings offer a new strategy, called 'photo-oxidation therapy', and provide a promising direction for the development of anti-cancer drugs. A research team led by scientists from City University of Hong Kong (CityU) has achieved a significant breakthrough by inventing a new class of near-infrared-activated photo-oxidants that can effectively kill cancer cells without requiring oxygen. The photo-oxidants induce a unique form of cancer cell death that can overcome cancer cell resistance. The findings offer a new strategy, called 'photo-oxidation therapy', and provide a promising direction for the development of anti-cancer drugs. Photodynamic therapy, an innovative cancer treatment approach, utilizes photosensitizers to generate reactive oxygen species (ROSs), which when irradiated by light, selectively kill cancer cells. However, most existing photodynamic therapies rely on the presence of oxygen, while solid cancer tumours often feature a hypoxic microenvironment with very low oxygen levels, limiting the therapeutic efficiency of this approach. To address this limitation, a research team led by Professor Zhu Guangyu, in the Department of Chemistry, and Professor He Mingliang, in the Department of Biomedical Sciences (BMS) at CityU, discovered an effect called "metal-enhanced photo-oxidation." By conjugating metals like platinum with organic photosensitive ligands, they significantly enhanced the photo-oxidation capability. This breakthrough led them to develop a new class of near-infrared-activated platinum(IV) photo-oxidants (Pt(IV) photo-oxidants) that can be activated by near-infrared (NIR) light to directly oxidize biomolecules and effectively kill cancer cells without the need for oxygen. In their experiments, the team administered Pt(IV) photo-oxidants to mice with tumours through intravenous injection. Four hours later, they applied near-infrared radiation to the mice to activate the photo-oxidants to attack the cancer cells. The results demonstrated a significant reduction in tumour volume and weight of 89% and 76%, respectively, indicating the potent tumour-inhibitory effect of the Pt(IV) photo-oxidants. "Intriguingly, we found that the 'death mode' of cancer cells induced by the Pt(IV) photo-oxidants differs from that of any other anticancer agents," said Professor Zhu. "A unique mode of cancer cell destruction was initiated through the dual-action effect of strong intracellular oxidative stress and reduced intracellular pH value." Their experimental data show that after the Pt(IV) photo-oxidants that accumulated in the endoplasmic reticulum inside the cancer cells were activated by near-infrared radiation, they vigorously oxidized crucial biomolecules inside the cancer cells without requiring oxygen, generating ROSs, lipid peroxides and protons. The ROSs and lipid peroxides then triggered intensive oxidative bursts, while the protons lowered the intracellular pH value, creating an unfavourable acidic microenvironment for the cancer cells. Moreover, their experiments confirmed that Pt(IV) photo-oxidants effectively activate the immune system in both in vitro and in vivo settings. The Pt(IV) photo-oxidants triggered immunogenic cell death, stimulating the proliferation and activation of immune cells. The number of T helper and T killer cells, which are crucial for triggering the body's immune response, in the mice treated with photoactivated Pt(IV) photo-oxidants increased by 7- and 23-fold, respectively, compared to the control group. "By inducing nonclassical necrosis, Pt(IV) photo-oxidants can overcome the resistance of cancer cells to traditional photodynamic therapies and chemotherapy agents, activate the immune system, and effectively eliminate cancer cells," explained Professor Zhu. "These findings serve as proof of concept and suggest that the development of photo-oxidants based on metal-enhanced photo-oxidation is a promising new direction for developing metal-based anticancer drugs," said Professor He. The research team plans to conduct preclinical studies to fully characterize the chemical, biological and pharmaceutical properties of the newly invented Pt(IV) photo-oxidants. Their ultimate goal is to identify lead compounds for clinical testing. The co-first authors of the study are Dr Deng Zhiqin and Dr Li Huangcan, both from CityU. The corresponding authors are Professor Zhu and Professor He. Collaborators from CityU include Professor Michael Yang Mengsu, Professor Lu Jian, Professor Li Yangyang, Professor Lo Pui-chi, Professor Lei Dangyuan, Dr Ou Weihui, Dr Wang Na, Dr Chen Shu and PhD students Mr Liu Gongyuan, Mr Xu Feijie and Mr Wang Xiong. The study received support from various funding sources, including the Hong Kong Research Grants Council, the National Natural Science Foundation of China, and the Science Technology and Innovation Committee of Shenzhen Municipality.

A research team has achieved a groundbreaking advancement in nanomaterials by successfully developing a highly efficient electrocatalyst which can enhance the generation of hydrogen significantly through electrochemical water splitting. This major breakthrough has great application potential for the clean energy industry. An international team led by City University of Hong Kong (CityU) has announced a groundbreaking step forward that has added significantly to the technical know-how required to clean up the planet. The discovery, published in the journal Nature, centres on developing a highly efficient electrocatalyst that can enhance hydrogen generation through electrocatalytic water splitting. Titled "Phase-dependent growth of Pt on MoS2 for highly efficient H2 evolution," the paper was published on 13 September in London. Cleaner energy sources are desperately needed, but the challenges in weaning the world off fossil fuels and onto more sustainable energies are enormous. "Hydrogen generated by electrocatalytic water splitting is regarded as one of the most promising clean energies for replacing fossil fuels in the near future, reducing environmental pollution and the greenhouse effect," said Professor Zhang Hua, Herman Hu Chair Professor of Nanomaterials at CityU, who is spearheading the research. Professor Zhang's collaborators include Professor Anthony R. J. Kucernak from the Department of Chemistry at Imperial College London and researchers from universities and research institutes in Hong Kong, mainland China, Singapore and the UK. The critical development in the CityU-led research is establishing novel catalysts by using the transition-metal dichalcogenide (TMD) nanosheets as supports, enabling superior efficiency and high stability during the electrocatalytic hydrogen evolution reaction (HER), a vital step in electrocatalytic water-splitting, also known as the water electrolysis technique, for hydrogen production. The team has been exploring how to enhance the performance of the HER process by engineering the crystal phase of nanomaterials for several years. Although TMD nanosheets with unconventional crystal phases possess great potential to be used as catalyst supports, fabricating such sheets pure enough for HER is far from straightforward. But in this research, Professor Zhang's team has developed a new method to prepare unconventional-phase TMD nanosheets with high phase-purity and quality. Furthermore, they have investigated the crystal phase-dependent growth of noble metals on the TMD nanosheet supports. Technically speaking, they found that the 2H-phase template facilitates the epitaxial growth of Pt nanoparticles, whereas the 1T′-phase template supports single-atomically dispersed Pt atoms (s-Pt). The synthesised s-Pt/1T′-MoS2 serves as a highly efficient catalyst for HER and can work for 500 hours in the water electrolyser, demonstrating that 1T′-TMD nanosheets could be effective supports for catalysts. "We will develop more efficient catalysts based on this finding and explore their applications in various catalytic reactions," said Dr Shi Zhenyu, a postdoctoral researcher in CityU's Department of Chemistry and the first author of the paper. These findings expand the scope of phase engineering in nanomaterials, paving the way for the design and synthesis of highly efficient catalysts, contributing to cleaner energies and more sustainable development.

A research team has recently made a significant advancement in spinal cord injury treatment by using genetically modified human neural stem cells (hNSCs). They found that specifically modulating a gene expression to a certain level in hNSCs can effectively promote the reconstruction of damaged neural circuits and restore locomotor functions, offering great potential for new therapeutic opportunities for patients with spinal cord injury. A research team co-led by City University of Hong Kong (CityU) and The University of Hong Kong (HKU) has recently made a significant advancement in spinal cord injury treatment by using genetically modified human neural stem cells (hNSCs). They found that specifically modulating a gene expression to a certain level in hNSCs can effectively promote the reconstruction of damaged neural circuits and restore locomotor functions, offering great potential for new therapeutic opportunities for patients with spinal cord injury. Traumatic spinal cord injury is a devastating condition that commonly results from accidents such as falls, car crashes or sport-related injuries. Spinal neurons with long axons play critical roles in transmitting signals between the brain and the rest of the body, controlling our movement and sensory perception. Spinal cord injury causes irreversible damage to neurons and axons, which significantly interrupts signal transmission, hence leading to defective locomotion and somatosensory functions. "Currently, there are no effective clinical management or treatment regimens for patients with spinal cord injury, often leaving them with lifelong disabilities," explained Professor Jessica Liu Aijia, Assistant Professor in the Department of Neuroscience at CityU and the co-leader of the research. "While recent progress has been made in promoting spinal cord regeneration through transplantation of hNSCs derived from human induced pluripotent stem cells, the degree of functional recovery obtained has been modest. This is largely due to the hostile micro-environment around the lesion site, such as the formation of barrier-like structures called astroglial scars and the lack of neurotrophic factors in adults for neuronal differentiation. These factors hinder functional neuronal regeneration, resulting in prolonged repairing and limited functional recovery." A gene -- SOX9 was reported with a high-level expression at the injury site in previous studies, and the gene itself is the leading cause of the glial scars' formation and the hindrance of neuronal survival and differentiation. To overcome the adverse effects of the post-injury micro-environment, the joint-research team engineered the transplanted neural stem cells with a graded reduction of SOX9 by approximately 50%. The genetically modified hNSCs expressing half-dose of SOX9 resulted in robust neuronal differentiation and maturation (a process by which immature cells in the nervous system become specialised nerve cells) after transplantation in a hostile microenvironment, promoting neural circuits reconstruction in the spinal cord within a shorter period of time. It also remarkably reduced glial scar accumulation, facilitating long-distance axon outgrowth. The team recorded a large number of axons extending more than 35mm at 3 months post-graft, while relatively less in number with shorter extensions to 25mm with non-modified neural stem cells. To further explore the therapeutic effects of the modified hNSCs in treating spinal cord injury, the research team used a severe spinal cord injury rat model to evaluate the locomotion recovery after transplantation, including grid walking and consecutive walk. The former recorded limb coordination, such as the capability to grasp a grid rung with correct placement, and the latter recorded stepping patterns to demonstrate their gait and fingertip motor ability. Compared to rats' graft with non-modified hNSCs, rats' graft with SOX9 gene-modified hNSCs performed much better in placing their affected hind paws on the grid, with fewer misdirected steps after 10 weeks post-injury. In addition, these treated rats demonstrated a good gait with clear paw position and toe movement when walking across a metre-long narrow corridor. "Our findings reveal a new treatment direction by using a genetically modified strategy to alter the grafts' response to the deleterious microenvironment in vivo after injury, improving cell tolerance to the niche and self-differentiation potential. This brings a new treatment direction for repairing damaged spinal cord," said Professor Liu. "This genetic modification of hNSCs, particularly those derived from patient-specific human-induced pluripotent stem cells, which can be generated from a patient's skin or blood cells, eliminates ethical concerns in using embryonic stem cells and minimises the risk of rejection by the immune system. It provides a more effective autologous stem cell therapy for severe traumatic spinal cord injury," she added.