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Nanoparticle therapeutics: an emerging treatment modality for cancer

Key Points

  • Nanoparticles are emerging as a new class of therapeutics for cancer because they can perform in ways that other therapeutic modalities cannot.

  • Newer nanoparticle therapeutics are showing enhanced efficacy with lower side effects than traditional small-molecule chemotherapeutics in early clinic studies, and are doing so without creating additional new side effects due to the nanoparticle.

  • Although there are many types of nanoparticles, few will have the proper attributes to reach clinical use because of the issues involved in translating research grade nanoparticles to clinic grade nanoparticles.

  • Newer nanoparticle therapeutics have a greater degree of multifunctionality and involve not only delivery to the tumour but intracellular delivery so that multidrug resistance can be bypassed and therapeutic agents such as siRNA that require intracellular delivery can be utilized.

  • Nanoparticles that contain cancer cell-surface targeting ligands are now in the clinic.

Abstract

Nanoparticles — particles in the size range 1–100 nm — are emerging as a class of therapeutics for cancer. Early clinical results suggest that nanoparticle therapeutics can show enhanced efficacy, while simultaneously reducing side effects, owing to properties such as more targeted localization in tumours and active cellular uptake. Here, we highlight the features of nanoparticle therapeutics that distinguish them from previous anticancer therapies, and describe how these features provide the potential for therapeutic effects that are not achievable with other modalities. While large numbers of preclinical studies have been published, the emphasis here is placed on preclinical and clinical studies that are likely to affect clinical investigations and their implications for advancing the treatment of patients with cancer.

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Figure 1: Major classes of nanoparticles that are in clinical trials and some of their properties.
Figure 2: Nanoparticles with numerous targeting ligands can provide multivalent binding to the surface of cells with high receptor density.
Figure 3: Nanoparticles can overcome surface efflux pump mediated drug resistance.

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Acknowledgements

This article is partially supported (Z.C. and D.M.S.) by a grant from the US National Cancer Institute, Center for Cancer Nanotechnology of Excellence (U54 CA119338).

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Correspondence to Mark E. Davis.

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Glossary

Clearance

This is the volume of blood/plasma cleared of the drug per time. Lower clearances are indicative of higher circulation times.

Neutropaenia

Neutropaenia, usually induced by chemotherapy, is a myelosuppression that involves mainly the neutrophil lineage of white blood cells. Severe (grade 3 or 4) neutropaenia with infection is life-threatening, which should be prevented by treatment with growth factors. For more information see the Common Toxicity Criteria at the US National Cancer Institute web site (see Further information).

Haematological toxicity

This includes suppression of red blood cells, white blood cells or platelet counts, and is usually induced by chemotherapeutic agents. Grade 4 toxicity, including severe anaemia, leucopaneia or thrombocytopaenia, requires immediate intervention to prevent life-threatening conditions. For more information see the Common Toxicity Criteria at the US National Cancer Institute web site (see Further information).

Cardiotoxicity

Cardiotoxicity is a toxicity that affects the heart functions. It includes arrhythmia, cardiac pumping dysfunction and eventually heart failure when it develops in severity. Grade 4 (severe) cardiotoxicity is associated with the life-threatening condition of arrhythmia or heart failure. For more information see the Common Toxicity Criteria at the US National Cancer Institute web site (see Further information).

Neuropathy

Neuropathy is a disorder of the nervous system that includes dysfunction of cranial, motor and sensory nerves. When grade 3 or 4 neuropathy is developed, it can significantly jeopardize normal functions. Severe neuropathy includes paralysis, paraesthesia and disabling cognitive impairments. For more information see the Common Toxicity Criteria at the US National Cancer Institute web site (see Further information).

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Davis, M., Chen, Z. & Shin, D. Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat Rev Drug Discov 7, 771–782 (2008). https://doi.org/10.1038/nrd2614

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