Abstract

Achievement of high targeting efficiency for a drug delivery system remains a challenge of tumor diagnoses and nonsurgery therapies. Although nanoparticle-based drug delivery systems have made great progress in extending circulation time, improving durability, and controlling drug release, the targeting efficiency remains low. And the development is limited to reducing side effects since overall survival rates are mostly unchanged. Therefore, great efforts have been made to explore cell-driven drug delivery systems in the tumor area. Cells, particularly those in the blood circulatory system, meet most of the demands that the nanoparticle-based delivery systems do not. These cells possess extended circulation times and innate chemomigration ability and can activate an immune response that exerts therapeutic effects. However, new challenges have emerged, such as payloads, cell function change, cargo leakage, and in situ release. Generally, employing cells from the blood circulatory system as cargo carriers has achieved great benefits and paved the way for tumor diagnosis and therapy. This review specifically covers (a) the properties of red blood cells, monocytes, macrophages, neutrophils, natural killer cells, T lymphocytes, and mesenchymal stem cells; (b) the loading strategies to balance cargo amounts and cell function balance; (c) the cascade strategies to improve cell-driven targeting delivery efficiency; and (d) the features and applications of cell membranes, artificial cells, and extracellular vesicles in cancer treatment.

Highlights

  • According to the World Health Organization (WHO) report in 2018, cancer remains one of the top 10 global causes of death [1]

  • Immune and stem cells can chemomigrate and transverse blood barriers, including the blood-brain barrier (BBB); they can penetrate the deep tumor matrix [18] instead of enhanced permeability and retention (EPR)-dependent intracellular extravasation [12]. These results have provided a new drug delivery system (DDS) and shed light on improving circulating and targeting delivery efficiency in vivo for cancer diagnosis and therapy

  • They can be recruited to sites via several tumor-related factors: (a) cancer-related cytokines (e.g., CSF-1, VEGF, and PDGF); (b) chemokines (e.g., CCL-2/5/7/8/12); (c) fibrinogen; and (d) fibronectin and other factors produced during extracellular matrix (ECM) cleavage (in Figure 1(b)) [26]

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Summary

Introduction

According to the World Health Organization (WHO) report in 2018, cancer remains one of the top 10 global causes of death [1]. From intravenous injection to tumor sites, cargo-loaded nanoparticles (NPs) go through a CAPIR cascade: Circulation, Accumulation, Penetration, Internalization, and Drug Release [4]. Immune and stem cells can chemomigrate and transverse blood barriers, including the BBB; they can penetrate the deep tumor matrix [18] instead of EPR-dependent intracellular extravasation [12]. These results have provided a new DDS and shed light on improving circulating and targeting delivery efficiency in vivo for cancer diagnosis and therapy. This article will focus on (a) the properties of circulatory cells, mainly red blood cells (RBCs), leukocytes, and mesenchymal stem cells (MSCs); (b) the loading strategies for balancing payload amounts and cell functions; (c) the cascade strategies for improving cell-driven targeting delivery efficiency; and (d) the cell membrane and small extracellular vesicles (EVs) as drug carriers for targeting delivery

Utilizable Properties of Circulatory Cells
Loading Strategies for Cargo Amounts and Cell Function Balance
Cascade Strategies for Improving Cell-Driven Targeting Delivery Efficiency
Cell Derivatives as Drug Carriers for Targeting Delivery
Cell Membrane
Challenges
Findings
Conclusion
Full Text
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