Oncotarget

Research Papers:

Engineered human platelet-derived microparticles as natural vectors for targeted drug delivery

Jyotsna Kailashiya, Vineeta Gupta and Debabrata Dash _

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Oncotarget. 2019; 10:5835-5846. https://doi.org/10.18632/oncotarget.27223

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Abstract

Jyotsna Kailashiya1, Vineeta Gupta2 and Debabrata Dash1

1 Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh 221005, India

2 Department of Pediatrics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh 221005, India

Correspondence to:

Debabrata Dash,email: ddash.biochem@gmail.com

Keywords: cancer targeting; drug-delivery vector; doxorubicin; leukemia; platelet-derived microparticles

Received: May 09, 2019     Accepted: September 10, 2019     Published: October 08, 2019

ABSTRACT

Drug targeting has opened a new paradigm in therapeutics with development of delivery vectors like liposomes and polymeric nanoparticles. Although their clinical application is crippled by limited biological adaptability. Off-target toxicity and biocompatibility still remains one of the critical problems in anticancer therapeutics that can be life-threatening. Here we report a quick, simple and facile method of engineering human platelets to generate drug loaded platelet-derived microparticles (PMPs) by top-down approach, which are biocompatible and naturally target leukemia cells. Drug loaded PMPs and cancer cell uptake were characterized by flow cytometry, confocal microscopy, Nanoparticle Tracking Analysis and fluorimetry. Effective drug delivery was tested in cancer cell lines as well as in clinical samples from leukemia patients. We explored that PMPs are capable of carrying multiple drug payloads, have long shelf life and can be harvested in large quantity in short period. Importantly, PMPs exhibited remarkably higher toxicity towards cancer cells than free drug and had lower escape into extravascular spaces. Transfer of drug to cancer cells of leukemia patients was significantly higher than free drug, when delivered through PMPs. Our experiments validated therapeutic application of PMPs as biocompatible drug delivery vector against cancer cells with minimal off-target delivery.


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PII: 27223