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KMID : 1146920210510050541
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Journal of Pharmaceutical Investigation
2021 Volume.51 No. 5 p.541 ~ p.553
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Tumor spheroid-based microtumor models for preclinical evaluation of anticancer nanomedicines
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Khawar Iftikhar Ali
Ghosh Torsha
Park Jong-Kook
Kuh Hyo-Jeong
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Abstract
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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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KEYWORD
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Nanomedicines, Anticancer therapeutics, Tumor microenvironment, Tumor spheroid-based microtumors, Extracellular matrix, Peclinical evalution, 3D Tumor model
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