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Drug Deliv. 2020 Dec;27(1):1-14. doi: 10.1080/10717544.2019.1701141.

Neutrophils, as "Trojan horses", participate in the delivery of therapeutical PLGA nanoparticles into a tumor based on the chemotactic effect.

Author information

1
College of Pharmacy, Shandong First Medical University & Shandong Academy of Medical Science, Taian, PR China.
2
The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine of Ministry of Education (KLOBM), School & Hospital of Stomatology, Wuhan University, Wuhan, PR China.
3
Institute of Immunology, Shandong First Medical University & Shandong Academy of Medical Science, Taian, PR China.
4
Shanghai Public Health Clinical Center, Fudan University, Shanghai, PR China.

Abstract

Inspired by the fact that leukocytes have innate phagocytic functions and oriented migration capabilities in response to chemoattractants, we have unveiled that endogenous neutrophils as "Trojan horses", participate in the delivery of nanoparticles in an "in vivo self-armed assembly" manner. Neutrophils were the main population to preferentially sequester the intravenous administrated nanoparticles with an average size of 260 nm. The pre-implantation of CXCL1-laden hydrogels could trigger and induce a targeted signal to attract an influx of neutrophils carrying the therapeutic goods to the desired position. In mouse models of melanoma, the combinatorial regimen of using the PLGA nanoparticles with the CXCL1 hydrogels exhibited superior tumor inhibition capability. This work leveraged the natural phagocytosis of neutrophile and the chemotactic effect of chemokines for targeted delivery. We believe this strategy will improve the therapeutic efficiency of nanoparticle-based delivery systems, especially when the chemokines are implanted at sites of surgical tumor removal, during cancer treatment at the clinic.

KEYWORDS:

Neutrophils; PLGA nanoparticles; Trojan horse; chemokines; paclitaxel

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