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Targeted drug delivery strategies for precision medicines

Abstract

Progress in the field of precision medicine has changed the landscape of cancer therapy. Precision medicine is propelled by technologies that enable molecular profiling, genomic analysis and optimized drug design to tailor treatments for individual patients. Although precision medicines have resulted in some clinical successes, the use of many potential therapeutics has been hindered by pharmacological issues, including toxicities and drug resistance. Drug delivery materials and approaches have now advanced to a point where they can enable the modulation of a drug’s pharmacological parameters, without compromising the desired effect on molecular targets. Specifically, they can modulate a drug’s pharmacokinetics, stability, absorption and exposure to tumours and healthy tissues, and facilitate the administration of synergistic drug combinations. This Review highlights recent progress in precision therapeutics and drug delivery, and identifies opportunities for strategies to improve the therapeutic index of cancer drugs and, consequently, clinical outcomes.

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Fig. 1: Major side effects of kinase inhibitors.
Fig. 2: Pharmacological properties of kinase inhibitors.
Fig. 3: Nanoscale delivery approaches for small-molecule cargoes.
Fig. 4: Delivery routes and targets in the tumour microenvironment.
Fig. 5: Organ targeting with drug delivery systems.
Fig. 6: Proposed patient selection and clinical correlate measurements for a precision drug nanomedicine trial.

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Acknowledgements

This work is supported, in part, by the NIH Director’s New Innovator Award (DP2-HD075698) and NIH grants R01-CA215719, R01-DK114321, R01-NS116353, R01-CA190642, UL1-TR002384, T32-CA062948 and P30-CA008748, the National Science Foundation (CAREER 1752506 and PHY 1545832), the American Cancer Society Research Scholar Grant (GC230452), the Pershing Square Sohn Cancer Research Alliance, the Breast Cancer Foundation, the Stand Up to Cancer Foundation, the Geoffrey Beene Cancer Research Center, the Expect Miracles Foundation - Financial Services Against Cancer, the Anna Fuller Fund, the Louis V. Gerstner Jr. Young Investigator’s Fund, the Frank A. Howard Scholars Program, the Honorable Tina Brozman Foundation for Ovarian Cancer Research, Cycle for Survival, the Alan and Sandra Gerry Metastasis and Tumor Ecosystems Center, Mr. William H. Goodwin and Mrs. Alice Goodwin and the Commonwealth Foundation for Cancer Research, the Center for Experimental Therapeutics, the Imaging & Radiation Sciences Program and the Center for Molecular Imaging and Nanotechnology of Memorial Sloan Kettering Cancer. Y.S. is a Jack Klein fellow. The opinions, results, findings and/or interpretations of data contained therein are the responsibility of the contractor and do not necessarily represent the opinions, interpretations or policy of the state or, if funded with federal funds, the applicable federal funding agency. Special thanks to S. D’Angelo for helpful discussions.

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M.T.M., Y.S. and H.K. contributed equally to the literature research for the article, creating figures, writing the manuscript and contributing to the discussion of the content. D.A.H., N.R. and M.S. discussed the content of the article and wrote perspective content relevant to their respective fields of expertise. D.A.H. conceived the article. All authors contributed to reviewing and editing the manuscript.

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Correspondence to Daniel A. Heller.

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D.A.H. is a co-founder and officer with equity interest in Goldilocks Therapeutics, Inc., LipidSense, Inc. and Nirova BioSense, Inc., as well as a member of the scientific advisory boards of Concarlo Holdings, LLC and Nanorobotics, Inc. M.S. is a full-time employee at AstraZeneca, has received research funds from Puma Biotechnology, AstraZeneca, Daiichi Sankyo, Immunomedics, Targimmune and Menarini Ricerche, is a co-founder of Medendi.org and is on the advisory board of Menarini Ricerche. N.R. is on the scientific advisory board (SAB) of Chugai, BeiGene, Fortress Biotech, Daiichi Sankyo, AstraZeneca, F-Prime, Zai Lab, Arvinas and Array BioPharma, and is a past SAB member of Millennium Takeda, Kadmon, Kura Oncology and Araxes. N.R. is also a consultant to Novartis Biomedical, Boehringer Ingelheim, Tarveda, Foresite Capital, Array BioPharma and Revolution Medicines, and, in recent years, has also consulted with Eli Lilly, Merrimack, Kura Oncology, Araxes and Kadmon. N.R. owns equity in BeiGene, Zai Lab, Fortress Biotech, Kura Oncology, Araxes, Kadmon and Effector. N.R. is a full-time employee at National Resilience Inc., collaborates with Plexxikon and receives research support from Chugai.

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Manzari, M.T., Shamay, Y., Kiguchi, H. et al. Targeted drug delivery strategies for precision medicines. Nat Rev Mater 6, 351–370 (2021). https://doi.org/10.1038/s41578-020-00269-6

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