Jianhua Liu1, Liantao Guo1, Yan Rao2, Weijie Zheng1, Dongcheng Gao1, Jing Zhang2, Lan Luo1, Xinwen Kuang1, Saraswati Sukumar3, Yi Tu1, Chuang Chen1, Shengrong Sun1. 1. Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China. 2. Animal Biosafety Level III Laboratory at the Center for Animal Experiment, Wuhan University School of Medicine, Wuhan, People's Republic of China. 3. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Abstract
Purpose: Triple-negative breast cancer (TNBC) is challenging to treat with traditional "standard of care" therapy due to the lack of targetable biomarkers and rapid progression to distant metastasis. Methods: We synthesized a novel combination regimen that included chemotherapy and photothermal therapy (PTT) to address this problem. Here, we tested a magnetic nanosystem (MNs-PEG/IR780-DOX micelles) loaded with the near-infrared (NIR) photothermal agent IR780 and doxorubicin (DOX) to achieve chemo-photothermal and boost antitumor immunity. Intraductal (i.duc) administration of MNs-PEG/IR780-DOX could increase the concentration of the drug in the tumor while reducing systemic side effects. Results: We showed more uptake of MNs-PEG/IR780-DOX by 4T1-luc cells and higher penetration in the tumor. MNs-PEG/IR780-DOX exhibited excellent photothermal conversion in vivo and in vitro. The release of DOX from MNs-PEG/IR780-DOX is pH- and temperature-sensitive. Facilitated by i.duc administration, MNs-PEG/IR780-DOX displayed antitumor effects and prevented distant organs metastasis under NIR laser (L) irradiation and magnetic field (MF)while avoiding DOX-induced toxicity. More importantly, MNs-PEG/IR780-DOX alleviated tumor immunosuppressive microenvironment by increasing tumor CD8+ T cells infiltration and reducing the proportion of myeloid-derived suppressor cells (MDSCs) and Tregs. Conclusion: Intraductal administration of pH- and temperature-sensitive MNs-PEG/IR780-DOX with L and MF had the potential for achieving minimally invasive, targeted, and accurate treatment of TNBC.
Purpose: Triple-negative breast cancer (TNBC) is challenging to treat with traditional "standard of care" therapy due to the lack of targetable biomarkers and rapid progression to distant metastasis. Methods: We synthesized a novel combination regimen that included chemotherapy and photothermal therapy (PTT) to address this problem. Here, we tested a magnetic nanosystem (MNs-PEG/IR780-DOX micelles) loaded with the near-infrared (NIR) photothermal agent IR780 and doxorubicin (DOX) to achieve chemo-photothermal and boost antitumor immunity. Intraductal (i.duc) administration of MNs-PEG/IR780-DOX could increase the concentration of the drug in the tumor while reducing systemic side effects. Results: We showed more uptake of MNs-PEG/IR780-DOX by 4T1-luc cells and higher penetration in the tumor. MNs-PEG/IR780-DOX exhibited excellent photothermal conversion in vivo and in vitro. The release of DOX from MNs-PEG/IR780-DOX is pH- and temperature-sensitive. Facilitated by i.duc administration, MNs-PEG/IR780-DOX displayed antitumor effects and prevented distant organs metastasis under NIR laser (L) irradiation and magnetic field (MF)while avoiding DOX-induced toxicity. More importantly, MNs-PEG/IR780-DOX alleviated tumor immunosuppressive microenvironment by increasing tumor CD8+ T cells infiltration and reducing the proportion of myeloid-derived suppressor cells (MDSCs) and Tregs. Conclusion: Intraductal administration of pH- and temperature-sensitive MNs-PEG/IR780-DOX with L and MF had the potential for achieving minimally invasive, targeted, and accurate treatment of TNBC.
Authors: Rajendar K Mittapalli; Xinli Liu; Chris E Adkins; Mohamed I Nounou; Kaci A Bohn; Tori B Terrell; Hussaini S Qhattal; Werner J Geldenhuys; Diane Palmieri; Patricia S Steeg; Quentin R Smith; Paul R Lockman Journal: Mol Cancer Ther Date: 2013-09-03 Impact factor: 6.261
Authors: Satoshi Murata; Scott L Kominsky; Mustafa Vali; Zhe Zhang; Elizabeth Garrett-Mayer; Dorian Korz; David Huso; Sharyn D Baker; James Barber; Elizabeth Jaffee; R Todd Reilly; Saraswati Sukumar Journal: Cancer Res Date: 2006-01-15 Impact factor: 12.701