Johnstone PA Sindelar WF Patterns
 Johnstone PA, Sindelar WF. Patterns of disease recurrence following defini-tive therapy of adenocarcinoma of the Spectinomycin using surgery and adjuvant radiotherapy: correlations of a clinical trial. Int J Radiat Oncol Biol Phys 1993;27:831–4.
 Bosset JF, Pavy JJ, Gillet M, Mantion G, Pelissier E, Schraub S. Conventional exter-nal irradiation alone as adjuvant treatment in resectable pancreatic cancer: results of a prospective study. Radiother Oncol 1992;24:191–4.
 Kalser MH, Ellenberg SS. Pancreatic cancer Adjuvant combined radia-tion and chemotherapy following curative resection. Arch Surg 1985;120: 899–903.
 Foo ML, Gunderson LL, Nagorney DM, Mcllrath DC, van Heerden JA, Robinow JS, et al. Patterns of failure in grossly resected pancreatic ductal adenocarcinoma treated with adjuvant irradiation ± 5 fluorouracil. Int J Radiat Oncol Biol Phys 1993;26:483–9.
 Dholakia AS, Kumar R, Raman SP, Moore JA, Ellsworth S, McNutt T, et al. Map-ping patterns of local recurrence after pancreaticoduodenectomy for pancreatic adenocarcinoma: a new approach to adjuvant radiation field design. Int J Radiat Oncol Biol Phys 2013;87:1007–15.
 Yu W, Hu W, Shui Y, Zhu X, Li C, Ren X, et al. Pancreatic cancer adjuvant radio-therapy target volume design: based on the postoperative local recurrence spatial location. Radiat Oncol 2016;11:138.
 Allen AM, Zalupski MM, Robertson JM, Eckhauser FE, Simone D, Brown D, et al. Adjuvant therapy in pancreatic cancer: phase I trial of radiation dose escalation with concurrent full-dose gemcitabine. Int J Radiat Oncol Biol Phys 2004;59:1461–7.
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Colloids and Surfaces B: Biointerfaces
journal homepage: www.elsevier.com/locate/colsurfb
A new drug carrier with oxygen generation function for modulating tumor T hypoxia microenvironment in cancer chemotherapy
Zhe Zhanga, Na Niua,b, , Xi Gaoa, Fuqin Hana, Zhijun Chenb, Shujun Lib, , Jian Lib
a College of Science, Northeast Forestry Universtiy, Harbin, 150001, PR China
b Key Laboratory of Bio-Based Materials Science and Technology, Ministry of Education, Northeast Forestry Universtiy, Harbin, 150001, PR China
Oxygen generation function
Drug release Magnetic Fe3O4 Au2O3
Hypoxia is the main characteristic of tumor microenvironment, and the one of the key factors that cause the drug resistance of cancer cells for chemotherapy. Anticancer drug such as DOX cannot react with suﬃcient oxygen to produce reactive oxygen species (ROS) in hypoxic environment, which aﬀects the therapeutic eﬃciency of the drug. In this work, we constructed a multi-functional nano-carrier (named as FeSiAuO) containing Fe3O4, me-soporous SiO2 and Au2O3 with magnetic, large surface ratio and light induced oxygen production properties. The Au2O3 may decompose into oxygen (O2) and Au under the light irradiation to improve the oxygen concentration of the microenvironment of cancer cells, which increases the sensitivity of cancer cells to drug (DOX), reduces the drug resistance, and eﬀectively exerts the anticancer eﬀect of DOX. Meanwhile, the release of the as-loaded DOX molecule from the porous of SiO2 will be also promoted under light irradiation in diverse pH conditions. With the helping of the magnet eﬀect of the Fe3O4, the DOX can be also targeted delivered to the tumor site under the magnetic field. All of above results were thoroughly examined by the cell and small animal assays, which demonstrate that the FeSiAuO can be served as the multifunctional drug nano-carrier to achieve the targeted high-eﬃcient cancer therapy.
At present, the precise diagnosis and eﬃcient treatment of cancer/ tumor have posed enormous challenges to researchers in the field of biomedicine [1–4]. As the main method of cancer treatment, the che-motherapy which refers to the treatment using chemical drugs such as doxorubicin (DOX) can react with intracellular oxygen to generate re-active oxygen species (ROS), and then kill or damage cancer cells, whose therapy eﬀect is relatively more obvious for now [5–9]. How-ever, drug therapy was seriously hindered in clinical application owning to its weakness of multi-drug resistance of tumor cell . One of the main reasons for drug resistance is the hypoxic microenviron-ment at the tumor site and within the tumor cells, which is derived from the formation mechanism of the tumor, including overgrowth of the cancer cells in the early stage, blood abnormalities during the neo-vascularization and overlong oxygen diﬀusion distance [11–15]. As for the DOX, its therapeutic eﬀect can be strongly decreased by the low oxygen concentration level of the cancer cells [16–19]. Therefore, in order to break through the diﬃcult point with resistance of tumor cells to DOX for cancer therapy, it is essential to take measures to increase