4.7 Review

An EPR-Independent extravasation Strategy: Deformable leukocytes as vehicles for improved solid tumor therapy

Journal

ADVANCED DRUG DELIVERY REVIEWS
Volume 187, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.addr.2022.114380

Keywords

Leukocyte-based Vehicles; Extravasation; EPR; Drug Delivery; Solid Tumor

Funding

  1. National Natural Science Foundation of China [81930099, 82130102, 92159304, 81773664, 82073785]
  2. Natural Science Foundation of Jiangsu Province [BK20212011]
  3. Double First-Class University project [CPU2018GY47]
  4. 111 Project from the Ministry of Education of China
  5. State Administration of Foreign Expert Affairs of China [111-2-07, B17047]
  6. Open Project of State Key Laboratory of Natural Medicines [SKLNMZZ202017, SKLNMKF202206]
  7. China National Postdoctoral Program for Innovation Talents [BX2021375]

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This article reviews the concept and applications of leukocytes as drug delivery vehicles. Leukocytes have the ability to cross the vessel wall and crawl through tissue interstitium, making them a promising delivery carrier.
Effective delivery of therapeutic modality throughout the tumorous nidus plays a crucial role in successful solid tumor treatment. However, conventional nanomedicines based on enhanced permeability and retention (EPR) effect have yielded limited delivery/therapeutic efficiency, due mainly to the heterogeneity of the solid tumor. Leukocytes, which could intrinsically migrate across the vessel wall and crawl through tissue interstitium in a self-deformable manner, have currently emerged as an alternative drug delivery vehicle. In this review, we start with the intrinsic properties of leukocytes (e.g., extravasation and crawling inside tumor), focusing on unveiling the conceptual rationality of leveraging leukocytes as EPR-independent delivery vehicles. Then we discussed various cargoes-loading/unloading strategies for leukocyte-based vehicles as well as their promising applications. This review aims to serve as an up-to-date compilation, which might provide inspiration for scientists in the field of drug delivery.(c) 2022 Elsevier B.V. All rights reserved.

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