Dr Xu’s research field has been focused on nanomaterials, nanobiotechnology, biomedicine and cancer therapy. He is one of the leading experts in the controlled preparation of anionic clay nanomaterials (hydrotalcite), and has done a lot of excellent investigations in biomedicine and plant protection. These include application of anionic clay nanomaterials to deliver drugs, genes and vaccines to animal and plant cells for synergistic functions, which provides useful means to protect the health of plants, animals and human beings. His research focuses in Shen Zhen Bay Laboratory include:

1.Multi-functional inorganic nanomaterials targeting the therapy of tumors, cardiovascular diseases and bone diseases；

2.Developing new therapy for combination cancer treatment using inorganic nanocarriers;

3.Cancer immunotherapy based on T cells activated with inorganic nanomaterials；

4.Effects of metal ions in inorganic nanomaterials on the immune system.

Professor Xu is a world-renowned scientist in nanobiotechnology and nanomedicine and one pioneering expert in the controlled preparation of clay nanomaterials (hydrotalcite, layered double hydroxide). He has developed several multifunctional nanoplatforms based on clay nanoparticles to effectively deliver drugs, genes and vaccines in vitro and in vivo for combination treatments of cancerous, infectious and cardiovascular diseases. He has published over 350 papers and book chapters, with the citation over 19,600 times and the H-index of 76 until the end of 2022. His research has been funded with over A$30 million together with his collaborators. He has filed 4 international patents, one of which has been transferred to an UK company for further developing Clay-non-steroidal anti-inflammatory drugs (NSAID) nanohybrids with the bitterness masked and side effects on the stomach and intestine minimized. The other patent is being now transferred to a listed pesticide company to develop BioClay systems as efficient gene-pesticide spray for crop protection against viruses and pests and increase the crop yield, without any damages to the ecosystem. These two products will generate huge benefits in economy and community.  

Four representative achievements are as follows：

1. Preparation of homogeneous suspensions of clay nanoparticles with the controlled particle size.

Prof Xu has developed a reliable yet simple approach to precisely control the clay particles with the average size in 20-2000 nm that are homogeneously dispersed as stable suspensions. This approach has been patented, and widely employed by many researchers to develop LDH nanoparticles as an efficient drug/gene/protein delivery system.

2. First discovery of clay nanoparticle being able to effectively deliver protein-based vaccines and elucidation of the mechanism

Prof Xu has found that clay nanoparticles are able to efficiently load protein-based vaccines. The subcutaneously injected nanovaccines durably promote the high level of specific antibodies, which effectively inhibit the proliferation of bacteria and the growth of tumor tissues. Further investigations have shown that clay nanoparticles stimulate the immune cells as nano-adjuvants and that nanovaccines form a much looser nodulus upon subcutaneous injection, which facilitates the recruitment of immune cells and the subsequent uptake of nanovaccines, generating long-term immune responses.

3. Development of novel combinations of cancer therapies based on clay nanoparticles

Prof Xu’s group has innovatively developed several clay-based nanoplatforms for the combination cancer therapy. These nanoplatforms have been demonstrated to be applied in several new cancer combination therapies, such as photothermo-chemo, photothermo-geno, light-driven gaso-chemo, ultrasound-driven gaso-chemo, and photo-immuno combination therapies. Combining two or more modules has significantly enhanced the treatment efficacy, reduced the therapeutic dose and promoted the long-term anti-cancer immunity. 

4. First innovation to use clay nanoparticle as vehicles to topically deliver dsRNA for crop protection against viruses and pests 

Prof Xu and his collaborators have for the first time demonstrated that sprayed clay nanoparticles carry and sustainably release dsRNA on the leaf surface to generate a long term (20-30 days) protection of plants from virus attack, in comparison with the short term (5-7 days) protection if naked dsRNA is sprayed in the same conditions. This breakthrough technology enables the clay-dsRNA nanohybrids into commercial products for efficient crop protection, which has been now under intensive investigations to develop the products by optimizing preparation conditions, scaling up production, enhancing the shelf stability and conducting glasshouse and field trials.  

Yang, XM; Lin, XD; Shi, W; Xie, SX; Huang, XN; Yin, SH; Jiang, XB; Hammock, BD; Xu, ZP*; Lu, XL*: “Nanobody-based bispecific T-cell engager (Nb-BiTE): a new platform for enhanced T-cell immunotherapy”. Signal Transduction and Targeted Therapy 8, 328, 2023.

Zhang, LX; Hou, SJ; Movahedi, F; Li, ZJ; Li, L; Hu, J; Jia, YB; Huang, YR; Zhu, J; Sun, XY; Zeng, LH; Liu, RT*; Xu, ZP*: “Amyloid-β/Tau burden and neuroinflammation dual-targeted nanomedicines synergistically restore memory and recognition of Alzheimer’s disease mice”. Nano Today 49, 101788, 2023.

Sun, LY; Gao, WD; Wang, JJ; Niu, XM; Kurniawan, N; Li, L*; Xu, ZP*: “A new sono-chemo sensitizer overcoming tumor hypoxia for augmented sono/chemo-dynamic therapy and robust immune-activating response”, Small 19, 2206078, 2023.

Zhang, LX; Jia, YB; Yang, JJ; Zhang, L; Hou, SJ; Niu, XY; Zhu, J; Huang, YR; Sun, XY; Xu, ZP*; Liu, RT*: “Efficient Immunotherapy of Drug-Free Layered Double Hydroxide Nanoparticles via Neutralizing Excess Acid and Blocking Tumor Cell Autophagy”. ACS Nano, 16, 12036-12048, 2022.

Sun, LY; Gao, WD; Liu, J; Wang, JJ; Li, L*; Yu, HJ; Xu, ZP*: “O2-Supplying Nanozymes Alleviate Hypoxia and Deplete Lactate to Eliminate Tumors and Activate Anti-Tumor Immunity”, ACS Appl. Mater. Interface 14, 56644–56657, 2022.

Liu, JP; Liu, K; Zhang, LM; Zhong, M; Hong, TL; Zhang, R; Gao, YF; Li, R; Xu, TF*; Xu, Z.P*: “Heat/pH-boosted release of 5-fluorouracil and albumin-bound paclitaxel from Cu-doped layered double hydroxide nanomedicine for synergistical chemo-photo-therapy of breast cancer”. J Control Release 335, 49-58, 2021.

Zhang, LX; Sun, XM; Jia, YB; Liu, XG; Dong, MD; Xu, ZP*; Liu, RT*: “Nanovaccine's Rapid Induction of Anti-tumor Immunity Significantly Improves Malignant Cancer Immunotherapy”. Nano Today 35, 100923, 2020.

Chen, WY; Zuo, HL; Li, B; Duan, C; Zhang, B; Rolfe, R; Mahony, TJ*; Xu, ZP*: “Clay nanoparticles elicit long-term immune responses by forming biodegradable depots for sustained antigen stimulation”, Small 14, e1704465, 2018.

Mitter, N*; Worrall, EA; Robinson, K; Li, P; Jain, RG; Taochy, C; Fletcher, SJ; Carroll, BJ; Lu, GQ; Xu, ZP*: “Clay nanosheets for stable delivery of RNA interference as a topical application to protect plants against viruses”. Nature Plants, 3, 16207, 2017.

Li, B; Gu, Z*; Kurniawan, N; Chen, WY; Xu ZP*: “Manganese-based Layered Double Hydroxide Nanoparticle as a T1-MRI Contrast Agent with Ultrasensitive pH Response and High Relaxivity”. Adv. Mater. 29, 201700373, 2017.