A multifunctional SN38-conjugated nanosystem for defeating myelosuppression and diarrhea induced by irinotecan in esophageal cancer. Issue 41 (16th October 2020)

• Record Type: Journal Article
• Authors: Chen, Jinjin; Zhou, Lulu; Wang, Chunhui; Sun, Yunhao; Lu, Yonglin; Li, Ruihao; Hu, Xiaochun; Chen, Mengyao; Chen, Lv; Chai, Keke; Yao, Tianming; Shi, Shuo; Dong, Chunyan
• Is Part Of: Nanoscale. Volume 12:Issue 41(2020)
• Page Start: 21234
• Page End: 21247
• Publication Date: 2020-10-16
• Subjects: Nanoscience -- Periodicals; Nanotechnology -- Periodicals; 620.505
• DOI: 10.1039/d0nr06266a
• Languages: English
• ISSNs: 2040-3364

Abstract

Abstract : A multifunctional tumor-targeting SN38-conjugated nanosystem was developed to defeat myelosuppression and diarrhea induced by irinotecan. 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 Mn 2+, thus enhancing oxygen-dependent PDT efficacy; meanwhile, Mn 2+ 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.