Breakthrough in macromolecular machines
The toxicity of anticancer drugs has spurred scientific innovation into developing technology for controlled targeted drug delivery and release to extirpate tumour cells with minimal damage to normal cells. A team of scholars from Faculty of Science achieved a world-first breakthrough with their design and synthesis of a smart globular macromolecular machine vehicle for actively controlled cancer drug delivery. The paper authored by the team comprising Associate Professor Dr Ken Leung, Founding Kwok Yat Wai Endowed Chair of Environmental and Biological Analysis Professor Cai Zongwei and PhD student Kwan Chak-shing of the Department of Chemistry; Head of Department of Physics Chair Professor Michel A Van Hove and former Postdoctoral Fellow Dr Zhao Rundong, was published in renowned journal Nature Communications.
The team synthesised a novel rotaxane dendrimer – interlocked molecules that combine a series of hyperbranched macromolecules with mechanical bonds at the branching unit. Mechanical bonds are a novel and exciting class of non-covalent bonds similar to familiar chains and hooks. Actively responding to acidic stimuli, these macromolecules produce an overall extension-contraction molecular motion via collective and controllable molecular back-and-forth shuttling, which gives them the ability to encapsulate drug molecules and release them. The type III-B with at most 15 mechanical bonds developed by the team possesses the most complicated molecular structure and exhibits the largest extension-contraction properties of all rotaxane dendrimers.
Life-saving bots working from within
Dr Ken Leung, who led the research, says the 15 mechanical bonds resemble 15 mechanical arms that actively control the delivery and suitable amount of drugs released to targeted cancer cells, tackling a major problem in current cancer therapy, such as leukemia treatment where the amount of drugs released to kill the free-floating cancer cells in the blood and bone marrow cannot be effectively controlled.
With its complexity and minute size, this synthetic molecule resembles a small virus. Due to its relative low toxicity, it could be left in the human body as an ideal long-term drug delivery molecular machine. The molecular masses of these new macromolecules were characterised by mass spectrometry, and their chemical structures and physical properties were also verified with supercomputer simulations.
Challenging but rewarding research
Kwan Chak-shing recounts how complicated the syntheses of macromolecular machines are and that the intermediate compounds require the formation of mechanical bonds followed by careful purification and characterisation using high-tech facilities. Despite the exacting process, the team is excited to be part of this research funded by the Area of Excellence Scheme of the University Grants Committee of Hong Kong, a Collaborative Research Fund of the Hong Kong Research Grants Council, and the HKBU Institute of Creativity which is supported by the Hung Hin Shiu Charitable Foundation. The team believes the breakthrough in the synthesis and the control of particle size of higher-generation rotaxane dendrimers could give scientists an insight to develop more sophisticated molecular machines to be applied in functional materials and nanotechnology, such as the delivery of drugs or biomolecules.
Click to learn more: