Innovation Center of NanoMedicine (iCONM; Center Director: Kazunori Kataoka; Location: Kawasaki, Japan) has announced with the Graduate School of Engineering of The University of Tokyo that a group led by Prof. Kanjiro Miyata, Visiting Scientist of iCONM (Professor, Department of Materials Engineering, The University of Tokyo), has found that the threshold for tissue permeability of brain tumours was in the range of 10−30 nm, using “Nanoruler” which is a biocompatible polymer used for measurement of “gaps in the body”.
Especially, by adjusting the size of the nanoruler to 10 nm, it achieves an unprecedentedly high brain tumour accumulation.
Obtained results have provided significant guidance for the design of future brain tumour nanomedicine.
Currently, there is no effective treatment for glioblastoma multiforme (GBM), the most frequent and malignant type of brain tumours.
Some low molecular weight antitumor agents are used to permeate the gaps between endothelial cells in the BBTB (Blood−Brain Tumor Barrier), which is a characteristic blood vessel structure and formed by the partial collapse of the blood−brain barrier, but they are rapidly excreted from the kidneys, resulting in low GBM accumulation.
Besides, their nonspecific distribution in healthy tissues often induces severe side effects such as myelosuppression and immunosuppression.
It is known that 30−100 nm-sized nanomedicines avoid rapid renal excretion and increase drug accumulation efficiency in some tumour models.
However, the GBM accumulation level of such nanomedicines remains limited, presumably because of the relatively low blood vessel permeability in the BBTB. Thus, Miyata et al. studied about size-dependent GBM targetability using a size-tunable stealth polymer, termed “polymeric nanoruler”, and reported the results in an international journal “Bioconjugate Chemistry” as follows:
Y. Ishibashi, M. Naito,* Y. Watanuki, M. Hori, S. Ogura, K. Taniwaki, M. Cho, R. Komiya, Y. Mochida, and K. Miyata*, Bioconjugate Chemistry, in press.
In conclusion, this study explored the size effect of nanomedicine on passive GBM targeting with size-tunable poly(ethylene glycol)-grafted copolymers (gPEGs) as polymeric nanorulers (ranging from 8.5 to 30 nm).
Small gPEGs exhibited efficient brain tumour accumulation, with 10 nm of gPEGs achieving the highest accumulation level (19 times higher than that in the normal brain region and 4.2 times higher than that of 30 nm of gPEGs), presumably because of the optimal size associated with enhanced BBTB permeability and prolonged blood circulation.
Miyata et al. will report the drug conjugation and optimisation for the enhanced GBM-targeted drug delivery in their future work.
Overall, this study provides a useful molecular design to develop GBM-targeted nanomedicines for chemotherapy, radiation therapy, photodynamic/thermal therapy, and diagnostics.
The novelty of this study
The future contribution of this study
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