2018-02-08
HKBU’s world-first breakthrough in macromolecular machines for actively controlled cancer drug delivery
Hong Kong Baptist University (HKBU) scholars demonstrated the
design and synthesis of a smart globular macromolecular machine vehicle
for actively controlled cancer drug delivery, which would enhance the
drug’s efficacy. This world-first breakthrough gives insight to targeted
therapy drugs such as Chlorambucil in the treatment of leukemia. The
paper entitled “Higher-Generation Type III-B Rotaxane Dendrimers with
Controlling Particle Size in Three-Dimensional Molecular Switching” was
published in renowned journal Nature Communications (DOI: 10.1038/s41467-018-02902-z).
All authors of the paper are from HKBU Faculty of Science. The team
comprises HKBU scholars in Chemistry and Physics: 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 Postdoctoral Fellow Dr Zhao
Rundong.
The team reported on a series of novel hyperbranched macromolecules with
at most 15 mechanical bonds at the branching unit: mechanical bonds are
a novel and exciting class of non-covalent bonds similar to familiar
chains and hooks, for example. These macromolecules can induce an
overall extension-contraction molecular motion via collective and
controllable molecular back-and-forth shuttling, providing the ability
to encapsulate drug molecules and release them actively by acidic
stimuli.
Dr Ken Leung, who led the research, said that in current leukemia
treatment, drugs are delivered to kill leukemia cells that may be
present in the blood and bone marrow. The amount of drugs released to
kill the free-floating cancer cells cannot be effectively controlled,
however. He said the 15 mechanical bonds resemble 15 mechanical arms
that actively control the delivery and suitable amount of drugs released
to targeted cancer cells.
Dr Leung added that this smart material combines molecular machines and
dendrimers with a new breakthrough in synthesis as well as controlled
and active drug release. With its complexity and size, this synthetic
molecule resembles a small virus. Due to the relatively low toxicity of
this smart globular molecular vehicle, it can also serve as a potential
ideal long-term drug delivery molecular machine submerged in the human
body. 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.
Kwan Chak-shing, who completed the synthesis of macromolecules, said, “I
am delighted that HKBU has all I need to complete this challenging
task. The syntheses of macromolecular machines are complicated whereas
the intermediate compounds require the formation of mechanical bonds
followed by careful purification and characterisation. I look forward to
seeing more creative research work done in HKBU.”
Molecular machines are assembled with their molecular counterparts that
are responsive to specific stimuli (input) and produce mechanical
movements (output). Rotaxane dendrimers are molecular interlocked
molecules that combine hyperbranched macromolecules with molecular
machines. Among various types of rotaxane dendrimer, type III-B
possesses the most complicated molecular structure and exhibits the
largest extension-contraction properties. 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.
This research is mainly 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.