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Tumor spheroid-based microtumor models for preclinical evaluation of anticancer nanomedicines

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Abstract

Background

Cancer nanomedicines (NMs) have emerged as potential anticancer therapeutics with advantages of tumor-targeting drug delivery for improved efficacy against human solid tumors. Despite promising data obtained in preclinical studies, few clinical trials have demonstrated successful results. The failure in the bench-to-bedside translation of NM efficacy may be related to the lack of clinical relevance of the tumor models used for preclinical screening and evaluation. Consideration of the pathophysiological factors that reduce drug distribution and activity in solid tumor tissues should be part of the selection of models used in preclinical evaluations of NMs.

Area covered

We briefly describe the fundamental concepts of NM targeting strategies and current issues related to their preclinical evaluation. We then provide an overview of the conventional and three-dimensional (3D) models utilized in preclinical evaluations of the target-site pharmacokinetics and pharmacodynamics of anticancer NMs. We further describe factors of the tumor microenvironment (TME) in solid tumors that significantly hinder the tissue distribution and therapeutic efficacy of anticancer drugs. Moreover, we focus on tumor spheroid (TS)-based microtumor models in terms of how they recapitulate TME conditions to represent a promising in vitro 3D tumor model for preclinical evaluations of anticancer NMs. Current state-of-the-art TS and TS-based microtumor generation methods are also reviewed.

Expert opinion

TS-based microtumors are promising in vitro models for the preclinical evaluation of NMs. The use of microtumor models is strongly recommended as the method of choice for the screening and evaluation of NMs with promising clinical efficacy.

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Funding

This research was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT (grant numbers 2019R1A5A2027588 and 2019R1A2B5B02070524).

Author information

Author notes

  1. Iftikhar Ali Khawar

    Present address: Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, Saint Louis, MO, USA

  2. Torsha Ghosh

    Present address: School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon, Republic of Korea

Authors and Affiliations

  1. Department of Biomedicine & Health Sciences, Graduate School, The Catholic University of Korea, Seoul, Republic of Korea

    Iftikhar Ali Khawar, Torsha Ghosh & Hyo-Jeong Kuh

  2. Department of Biomedical Science, Research Institute for Bioscience & Biotechnology, Hallym University, Chuncheon, Gangwon-do, Republic of Korea

    Jong Kook Park

  3. Department of Medical Life Sciences, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 137-701, Republic of Korea

    Hyo-Jeong Kuh

Authors
  1. Iftikhar Ali Khawar
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  2. Torsha Ghosh
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  3. Jong Kook Park
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  4. Hyo-Jeong Kuh
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Corresponding author

Correspondence to Hyo-Jeong Kuh.

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All the authors (I. A. Khawar, T. Gosh, J. K. Park and H. J. Kuh) declare that they have no conflict of interest.

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Khawar, I.A., Ghosh, T., Park, J.K. et al. Tumor spheroid-based microtumor models for preclinical evaluation of anticancer nanomedicines. J. Pharm. Investig. 51, 541–553 (2021). https://doi.org/10.1007/s40005-021-00534-y

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