Molecular Machines Make Drug Delivery More Precise

Researchers in Hong Kong have developed macromolecules with ‘mechanical arms’ that can actively control the delivery of drugs released to targeted cancer cells.

AsianScientist (Feb. 16, 2018) – In a study published in Nature Communications, researchers in Hong Kong have designed and synthesized a molecular machine that helps deliver cancer drugs specifically to tumor sites.

Molecular machines are assembled with their molecular counterparts that are responsive to specific stimuli (input) and produce mechanical movements (output). This makes them ideal for delivering drug cargo to tumors which offer different inputs than normal tissue.

In this study, a research group led by Associate Professor Dr Ken Leung Cham-fai at the Hong Kong Baptist University created a smart globular macromolecular machine vehicle for actively controlled cancer drug delivery.

The team reported 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 analogous to chains and hooks. 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.

Leung 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 noted that the 15 mechanical bonds resemble 15 ‘mechanical arms’ that actively control the delivery and suitable amount of drugs released to targeted cancer cells.

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 characterized by mass spectrometry, and their chemical structures and physical properties were also verified with supercomputer simulations.

The researchers hope that their method of synthesis and control of particle size will give scientists insights into developing more sophisticated molecular machines to be applied in functional materials and nanotechnology.

The article can be found at: Kwan et al. (2018) Higher-generation Type III-B Rotaxane Dendrimers with Controlling Particle Size in Three-dimensional Molecular Switching.


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Source: Hong Kong Baptist University; Photo: Shutterstock.
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