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DRUG DELIVERY

Ultrastable micelles boost chemotherapy

Nature Biomedical Engineering volume 2, pages 273–274 (2018)Cite this article

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Micelles of a superhydrophilic zwitterionic polymer covalently linked to a superhydrophobic lipid remain stable at extremely dilute conditions and enhance the delivery of hydrophobic chemotherapeutics in vivo.

Cao and co-authors’ lipid–zwitterionic-polymer9, which consists of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) and poly(carboxybetaine) (PCB), suggests that the ultrastability of its micelles is a consequence of ‘polarity contrast’, which for DSPE–PCB is drastically sharper than for most conventional surfactant molecules. The authors show that DSPE–PCB with a molecular weight of 5,000 for PCB (DSPE–PCB 5K) has a CMC that is below 2.7 × 10–6 mM. Such ultralow CMC is at least four orders of magnitude lower than the CMCs of commonly used surfactants, such as the non-ionic polysorbate 80 (CMC = 0.012 mM) and sodium dodecyl sulfate (CMC = 8.2 mM), and cannot be measured by the pyrene fluorescence probe method (considered to be the most sensitive and precise method for CMC determination10) because the final concentration for pyrene must be maintained at 6 × 10–4 mM to provide fluorescence spectra of good quality (a micellar concentration below 10–4 mM cannot significantly change the aggregation behaviour and fluorescence spectrum of pyrene). To measure low CMCs, the authors designed a method that involved diluting and then concentrating DSPE–PCB micelles stabilizing insoluble gold nanoparticles (AuNPs). If the micelles disassembled, the AuNPs would aggregate to larger sizes, which could be reflected by dynamic light scattering or ultraviolet–visible spectroscopic measurements after concentrating the samples by evaporating water at 35 °C under reduced pressure. Because the strong aggregation of hydrophobic AuNPs cannot be reversed via concentration of the sample, this method serves as an indirect measurement of the CMC. The authors verified that the method reliably detects the CMCs of commercially available surfactants. For DSPE–PCB 5K, however, they could not determine its CMC, as lowering the detection limit below 2.7 × 10–6 mM required an impracticably large container.

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Fig. 1: Ultrastable micelles of the DSPE–PCB 5K surfactant enhance the delivery of the anticancer drug docetaxel in melanoma tumours.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore

    Yuting Wen & Jun Li

  2. NUS Graduate School for Integrative Sciences and Engineering (NGS), National University of Singapore, Singapore, Singapore

    Jun Li

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  1. Yuting Wen
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  2. Jun Li
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Correspondence to Jun Li.

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Wen, Y., Li, J. Ultrastable micelles boost chemotherapy. Nat Biomed Eng 2, 273–274 (2018). https://doi.org/10.1038/s41551-018-0238-6

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