Review Article | Published:

Cancer nanomedicine: progress, challenges and opportunities

Nature Reviews Cancer volume 17, pages 2037 (2017) | Download Citation

Abstract

The intrinsic limits of conventional cancer therapies prompted the development and application of various nanotechnologies for more effective and safer cancer treatment, herein referred to as cancer nanomedicine. Considerable technological success has been achieved in this field, but the main obstacles to nanomedicine becoming a new paradigm in cancer therapy stem from the complexities and heterogeneity of tumour biology, an incomplete understanding of nano–bio interactions and the challenges regarding chemistry, manufacturing and controls required for clinical translation and commercialization. This Review highlights the progress, challenges and opportunities in cancer nanomedicine and discusses novel engineering approaches that capitalize on our growing understanding of tumour biology and nano–bio interactions to develop more effective nanotherapeutics for cancer patients.

Key points

  • Although first-generation cancer nanomedicines have been in clinical practice for more than 20 years, the total number of papers related to 'nanoparticle' on PubMed nearly doubled every 2 years between 2000 and 2014, and more than half of the papers on nanoparticles have been published in the past 5 years, indicating that our knowledge and arsenal of cancer nanomedicines is rapidly expanding.

  • Cancer nanomedicines accumulate in solid tumours through the enhanced permeability and retention (EPR) effect, which is increasingly appreciated to be complex, dynamic and heterogeneous across tumours and even within the same tumour.

  • Identifying biomarkers for the EPR effect may enable selection of cancer patients most likely to benefit from nanotherapeutics, prompting the development of personalized nanomedicine.

  • Effective systemic delivery of nanotherapeutics to solid tumours requires a deeper understanding of the biological factors involved, such as nanoparticle–protein interaction, blood circulation, extravasation to and interaction with the perivascular tumour microenvironment (TME), tumour tissue penetration, tumour cell internalization and intracellular trafficking.

  • The physicochemical properties of nanotherapeutics (for example, size, geometry, surface features, elasticity, stiffness, porosity, composition, targeting ligand and drug release kinetics) affect systemic delivery to tumours, thus determining the EPR effect and therapeutic outcomes.

  • Targeting the TME and the premetastatic niche with nanotechnologies offers another promising strategy for cancer therapy.

  • Addressing the challenges of controllable, reproducible and scalable nanoparticle synthesis will facilitate the clinical translation of cancer nanomedicines.

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Acknowledgements

We thank R. Weissleder, R. K. Jain, U. H. von Andrian and M. Mahmoudi for helpful discussions. This work was supported by the grants US National Institutes of Health (NIH) CA151884 (O.C.F.), EB015419 (O.C.F.), R00CA160350 (J.S.) and CA200900 (J.S.); US Department of Defense (DoD) Prostate Cancer Research Program (PCRP) Synergistic Idea Development Award W81XWH-15-1-0728 (O.C.F. and J.S.); David Koch–Prostate Cancer Foundation (PCF) Award in Nanotherapeutics (O.C.F. and P.W.K.); Movember–PCF Challenge Award (O.C.F. and J.S.); PCF Young Investigator Award (J.S.); and National Research Foundation of Korea (K1A1A2048701) (O.C.F.).

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Affiliations

  1. Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.

    • Jinjun Shi
    •  & Omid C. Farokhzad
  2. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.

    • Philip W. Kantoff
  3. Tarveda Therapeutics, Watertown, Massachusetts 02472, USA.

    • Richard Wooster
  4. King Abdulaziz University, Jeddah 21589, Saudi Arabia.

    • Omid C. Farokhzad

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Competing interests

O.C.F. declares financial interests in Selecta Biosciences, Tarveda Therapeutics and Placon Therapeutics. P.W.K. has financial interest in Tarveda Therapeutics. R.W. is an employee and shareholder of Tarveda Therapeutics.

Corresponding author

Correspondence to Omid C. Farokhzad.

Glossary

Nanoparticle

(NP). Particle of any shape with dimensions in the 1–100 nm range, as defined by the International Union of Pure and Applied Chemistry (IUPAC). Despite this size restriction, the term nanoparticles commonly applies to structures that are up to several hundred nanometres in size, although key is that design of the nanostructure produces a unique function and property.

Enhanced permeability and retention (EPR) effect

The mechanism resulting from pathophysiological processes (for example, leaky tumour vasculature, poor lymphatic drainage and tumour microenvironment interactions) that leads to the accumulation and retention of nanoparticles or macromolecules in tumours.

Nano–bio interactions

The interactions between nanoparticles and biological systems (for example, serum proteins, extracellular matrix, cells and organelles) that determine the biological fates of nanoparticles, such as circulation half-life, biodistribution, tumour accumulation, tumour cell internalization and tumour microenvironment distribution.

Excipients

Substances other than the active pharmaceutical ingredient (API) that are included in the manufacturing process of a medication or are contained in a finished pharmaceutical product dosage form.

Cmax

The maximum serum concentration that a drug or nanoparticle achieves after administration.

Area under the curve

(AUC). The area between the curve and the x-axis in a plot of drug or nanoparticle blood plasma concentration against time.

Payloads

The therapeutic or diagnostic agents carried by nanoparticles.

Opsonins

Plasma proteins (for example, immunoglobulins, complement proteins and fibrinogen) that coat a foreign particle to facilitate its uptake and destruction by phagocytic cells.

Mononuclear phagocyte system

(MPS). Part of the immune system composed of scavenging monocytes and macrophages, located in reticular connective tissue surrounding, for example, the liver, spleen, lung and bone marrow.

Nanomics

The collective study and characterization of the interactions between nanomaterials and biological systems.

Circulation half-life

The period required for drugs or nanoparticles in the blood to be reduced by one-half of a given concentration or amount.

Oncotic pressure

A form of osmotic pressure exerted by colloids in a solution, such as proteins in the plasma of a blood vessel.

Polydispersity

The heterogeneity of particle or molecule size in a mixture.

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DOI

https://doi.org/10.1038/nrc.2016.108

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