Analysis of nanoparticle delivery to tumours

Abstract

Targeting nanoparticles to malignant tissues for improved diagnosis and therapy is a popular concept. However, after surveying the literature from the past 10 years, only 0.7% (median) of the administered nanoparticle dose is found to be delivered to a solid tumour. This has negative consequences on the translation of nanotechnology for human use with respect to manufacturing, cost, toxicity, and imaging and therapeutic efficacy. In this article, we conduct a multivariate analysis on the compiled data to reveal the contributions of nanoparticle physicochemical parameters, tumour models and cancer types on the low delivery efficiency. We explore the potential causes of the poor delivery efficiency from the perspectives of tumour biology (intercellular versus transcellular transport, enhanced permeability and retention effect, and physicochemical-dependent nanoparticle transport through the tumour stroma) as well as competing organs (mononuclear phagocytic and renal systems) and present a 30-year research strategy to overcome this fundamental limitation. Solving the nanoparticle delivery problem will accelerate the clinical translation of nanomedicine.

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Figure 1: Analysis of nanoparticle delivery efficiency to solid tumours from studies published in 2005–2015.
Figure 2: Estimation of nanoparticle dose for human tumour treatment.
Figure 3: Tumour blood vessels and mode for nanoparticle extravasation in mother vessels versus capillaries.
Figure 4: Mechanisms for nanoparticle elimination from the bloodstream.
Figure 5: Proposed 30-year strategy for nanoparticle delivery research.

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Acknowledgements

The authors thank all authors of the studies that were surveyed for providing additional information on request to calculate the nanoparticle delivery efficiencies (Supplementary information S1 (table)).The authors thank M. Samarakoon and A. Göpferich for fruitful discussions. The authors also thank S. Patel, M. Chalsev, A. Mahmood, J. D. Mora, and Y. Y. Chen for creating the database system. W.C.W.C. acknowledges the Canadian Institutes of Health Research (CIHR), Natural Sciences and Engineering Research Council (NSERC), and Prostate Cancer Canada for supporting his research program. H.F.D. acknowledges financial support from the US National Institutes of Health (NIH) grant P01 CA92644 and by a contract from the National Foundation for Cancer Research. S.O. acknowledges the Japan Society for the Promotion of Science (JSPS) for a Research Fellowship (PD, No. 5621) and the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan for a Grant-in-Aid for Young Scientists (B) (No. 26820356).

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Correspondence to Warren C. W. Chan.

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Wilhelm, S., Tavares, A., Dai, Q. et al. Analysis of nanoparticle delivery to tumours. Nat Rev Mater 1, 16014 (2016). https://doi.org/10.1038/natrevmats.2016.14

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