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Issue 7, 2018

Transglutaminase mediated PEGylation of nanobodies for targeted nano-drug delivery

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Abstract

Targeted delivery of anticancer drugs that selectively accumulate in malignant cells could enhance drug efficacy and reduce side effects of conventional chemotherapy. In this work, we designed a single domain antibody (nanobody) based drug delivery system for targeted delivery of anticancer drugs. An anti-EGFR nanobody (Nb) was constructed with a C3-tag and a Q-tag for site specific modifications under physiological conditions. The site specific PEGylation of the nanobody was achieved via a transglutaminase catalyzed reaction through the coupling of the Q-tag with PEG-NH2. As a proof of concept, the PEGylated nanobody was tethered to HSA coated upconversion nanoparticles (UCNPs) through the C3-tag, and an anticancer drug, doxorubicin (DOX), was loaded. Results showed that the Nb-conjugated drug delivery system exhibits superior specificity to the EGFR positive tumor cells. The drug delivery system is highly accumulated in the EGFR positive tumor cells (A431), whereas there was no detectable accumulation in the EGFR negative cells (MCF-7). Consequently, the drug loaded particles demonstrated significantly higher anti-proliferation to A431 cells than to MCF-7 cells. This work provides an effective approach for site-specific modification of nanobodies for the construction of targeted drug delivery systems.

Graphical abstract: Transglutaminase mediated PEGylation of nanobodies for targeted nano-drug delivery

Supplementary files

Article information


Submitted
04 Dec 2017
Accepted
16 Jan 2018
First published
17 Jan 2018

J. Mater. Chem. B, 2018,6, 1011-1017
Article type
Paper

Transglutaminase mediated PEGylation of nanobodies for targeted nano-drug delivery

T. Wu, H. Huang, Y. Sheng, H. Shi, Y. Min and Y. Liu, J. Mater. Chem. B, 2018, 6, 1011 DOI: 10.1039/C7TB03132G

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