cRGD-Conjugated Fe3O4@PDA-DOX Multifunctional Nanocomposites…

cRGD-Conjugated Fe3O4@PDA-DOX Multifunctional Nanocomposites for MRI and Antitumor Chemo-Photothermal Therapy Xi Fan,1,2,* Zeting Yuan,1,* Chenting Shou,3,* Guohua Fan,1 Hong Wang,2 Feng Gao,3 Yuanpeng Rui,4 Ke Xu,1 Peihao Yin1,2,5,6 1Interventional Cancer Institute of Chinese Integrative Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2School of Medicine and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 3Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology, Shanghai, People’s Republic of China; 4Department of Image, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 5Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 6Shanghai Putuo Central School of Clinical Medicine, Anhui Medical University, Anhui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peihao YinDepartment of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of ChinaTel +86-21-2223 3836Fax +86-21-5266 5957Email yinpeihao@shutcm.edu.cnKe XuInterventional Cancer Institute of Chinese Integrative Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of ChinaTel +86-21-2223 3222Email kexu2577@shutcm.edu.cnBackground: Photothermal therapy (PTT) has great potential in the clinical treatment of tumors. However, most photothermal materials are difficult to apply due to their insufficient photothermal conversion efficiencies (PCEs), poor photostabilities and short circulation times. Furthermore, tumor recurrence is likely to occur using PTT only. In the present study, we prepared cyclo (Arg-Gly-Asp-d-Phe-Cys) [c(RGD)] conjugated doxorubicin (DOX)-loaded Fe3O4@polydopamine (PDA) nanoparticles to develop a multifunctional-targeted nanocomplex for integrated tumor diagnosis and treatment.Materials and methods: Cytotoxicity of Fe3O4@PDA-PEG-cRGD-DOX against HCT-116 cells was determined by cck-8 assay. Cellular uptake was measured by confocal laser scanning microscope (CLSM). Pharmacokinetic performance of DOX was evaluated to compare the differences between free DOX and DOX in nanocarrier. Performance in magnetic resonance imaging (MRI) and antitumor activity of complex nanoparticles were evaluated in tumor-bearing nude mice.Results: Fe3O4@PDA-PEG-cRGD-DOX has a particle size of 200–300 nm and a zeta potential of 22.7 mV. Further studies in vitro and in vivo demonstrated their excellent capacity to target tumor cells and promote drug internalization, and significantly higher cytotoxicity with respect to that seen in a control group was shown for the nanoparticles. In addition, they have good thermal stability, photothermal conversion efficiencies (PCEs) and pH responsiveness, releasing more DOX in a mildly acidic environment, which is very conducive to their chemotherapeutic effectiveness in the tumor microenvironment. Fe3O4@PDA-PEG-cRGD-DOX NPs were used in a subcutaneous xenograft tumor model of nude mouse HCT-116 cells showed clear signal contrast in T2-weighted images and effective anti-tumor chemo-photothermal therapy under NIR irradiation.Conclusion: According to our results, Fe3O4@PDA-PEG-cRGD-DOX had a satisfactory antitumor effect on colon cancer in nude mice and could be further developed as a potential integrated platform for the diagnosis and treatment of cancer to improve its antitumor activity against colon cancer.Keywords: Fe3O4 nanoparticles, polydopamine, cRGD, magnetic resonance imaging, MRI, chemo-photothermal therapy, tumor target

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