Lectin-Mediated pH-Sensitive Doxorubicin Prodrug for Pre-Targeted Chemotherapy of Colorectal Cancer with Enhanced Efficacy and Reduced Side Effects

Theranostics
Meinan YaoFan Wang

Abstract

Doxorubicin (DOX) has been clinically used as a broad-spectrum chemotherapeutic agent for decades, but its clinical application is hindered by the lack of tumour specificity, severe cardiotoxicity and haematotoxicity. Pre-targeted strategies are highly tumour-specific, therapeutic approaches. Herein, a novel pre-targeted system was constructed, aiming to enhance anticancer efficacy of DOX and maximally reduce its side effects. Methods: The DOX prodrug (bDOX) was first synthesized by conjugating DOX with mini-PEGylated (mPEGylated) biotin through a pH-sensitive bond. During the pre-targeted treatment, avidin was first administrated. After an optimized interval, bDOX was second administrated. The nontoxic prodrug bDOX was eventually transformed into the toxic anticancer form (DOX) by a pH-triggered cleavage specifically in tumour cells. The drug efficacy and side effect of the two-step, pre-targeted treatment were fully compared with free DOX in vitro and in vivo. Results: The prodrug bDOX was quite stable under neutral conditions and nearly nontoxic, but was immediately transformed into the toxic anticancer form (DOX) under acidic conditions. Compared to free DOX, the pre-targeted bDOX exhibited a higher cellular uptake by human...Continue Reading

Citations

Aug 15, 2020·Frontiers in Oncology·Sudath Hapuarachchige, Dmitri Artemov
Apr 23, 2021·Life Sciences·Sruthi Sritharan, Nageswaran Sivalingam

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Methods Mentioned

BETA
ELISA
flow cytometry
bioluminescence imaging
xenografts
fluorescence imaging

Software Mentioned

GraphPad Prism
Prism

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