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A multifunctional SN38-conjugated nanosystem for defeating myelosuppression and diarrhea induced by irinotecan in esophageal cancer

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Abstract

A combination of chemotherapy and phototherapy has been proposed as a promising treatment for esophageal cancer (EC). Irinotecan as a first-line treatment option is widely prescribed for metastatic EC, however, its clinical application is extremely restricted by the low conversion rate to SN38, severe myelosuppression and diarrhea. As a more potent active metabolite of irinotecan, SN38 is a better substitution for irinotecan, but the poor water solubility and the difficulty of encapsulation hindered its medical application. Herein, a multifunctional SN38-conjugated nanosystem (FA-PDA@PZM/SN38@BSA-MnO2, denoted as FA-PPSM) is designed for overcoming the above-mentioned drawbacks and achieving collaborative chemotherapy, photodynamic therapy (PDT) and photothermal therapy (PTT). The tumor acidic microenvironment induces decomposition of BSA-MnO2 nanoparticles into O2 and Mn2+, thus enhancing oxygen-dependent PDT efficacy; meanwhile, Mn2+ can be employed as a magnetic resonance imaging (MRI) contrast agent. Under 650 and 808 nm laser irradiation, the FA-PPSM nanocomposites exhibit superior antitumor efficacy in Eca-109-tumor bearing mice. Notably, there is low gastrointestinal toxicity and myelosuppression in the FA-PPSM treated mice compared with those treated with irinotecan (alone). Taken together, this work highlights the great potential of the FA-PPSM nanocomposites for MRI-guided chemotherapy in combination with endoscopic light therapy for esophageal cancer.

Graphical abstract: A multifunctional SN38-conjugated nanosystem for defeating myelosuppression and diarrhea induced by irinotecan in esophageal cancer

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Supplementary files

Article information


Submitted
30 Aug 2020
Accepted
20 Sep 2020
First published
21 Sep 2020

Nanoscale, 2020, Advance Article
Article type
Paper

A multifunctional SN38-conjugated nanosystem for defeating myelosuppression and diarrhea induced by irinotecan in esophageal cancer

J. Chen, L. Zhou, C. Wang, Y. Sun, Y. Lu, R. Li, X. Hu, M. Chen, L. Chen, K. Chai, T. Yao, S. Shi and C. Dong, Nanoscale, 2020, Advance Article , DOI: 10.1039/D0NR06266A

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