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Tumor metastases account for about 90% of cancer-related death, among which lymphatic metastases play a pivotal role. Therefore, high-efficiency sentinel lymph node (SLN) identification is significant for lymph node (LN) metastasis diagnosis in clinic. Herein, a novel in vivo covalent albumin-binding near-infrared (NIR) fluorescent IR820-maleimide conjugate (IR-Mal) is firstly designed as a SLN dual-mode imaging agent. The IR-Mal conjugate exhibits bright blue appearance and its large Stokes shift (over 100 nm) increases the fluorescent imaging resolution effectively. The fluorescence intensity of covalent albumin-binding IR-Mal (BSA-IR-Mal) complex is considerably stronger than that of IR-Mal. In vivo, IR-Mal could rapidly covalently bind the tissue interstitial albumin following subcutaneous administration and BSA-IR-Mal complexes could specifically accumulate on LN, and detect both normal and metastatic SLN through naked-eye and fluorescence imaging with high resolution. Moreover, the light stability and enhanced fluorescence intensity of BSA-IR-Mal complex facilitates its diagnosis accuracy. These findings suggest that such in vivo irreversible albumin-binding fluorescence conjugates could serve as a new agent for dual-mode imaging and have a great potential to be applied in the SLNs imaging and diagnosis., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Patients suffering from cancer have benefited from combination therapy. Nanocarriers are the ideal candidates for combination therapy. In this study, we constructed docetaxel (DTX) loaded micellar nanomedicines co-loaded with near infrared (NIR) dye-IR820 for photothermal therapy (PTT)/photodynamic therapy (PDT)/chemotherapy of breast cancer. Lyp-1, a tumor homing peptide, was introduced into the nanosystems to construct the active targeting nanomedicine. In order to deliver IR820 to the tumor site and overcome its short lifetime in vivo, a PEI derivative-PCL-g-PEI was introduced. IR820 with negative charge was formed stable static interaction with the amine groups, meanwhile, the absorption of IR820 in the NIR region was weakened. It indicated that the nanosystem constructed in this study may provide an alternative candidate for mild PTT. By the evaluation of the photothermal conversion in vivo, we can confirm that IR820 has been successfully delivered and effectively accumulated in the tumor site. Furthermore, the tumor cells targeting and anticancer performances of this nanosystem have been studied in vitro and in vivo. The results demonstrated Lyp-1 modification has enhanced the tumor targeting delivery of DTX and IR820. By combining PTT and PDT, DTX nanomedicine efficiently inhibited the growth and metastasis of breast cancer in mice. This nanosystem is a promising candidate for combination therapy of breast cancer., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Nanoparticle-assisted two-photon imaging and near infrared (NIR) imaging are two important technologies in biophotonics research. In the present paper, organically modified silica (ORMOSIL) nanoparticles encapsulated with either PpIX (protoporphyrin IX) photosensitizers or IR-820 NIR fluorophores were synthesized and optically characterized. Using the former ORMOSIL nanoparticles, we showed: (i) direct excitation of the fluorescence of PpIX through its efficient two-photon absorption in the intracellular environment of tumor cells, and (ii) cytotoxicity towards tumor cells by PpIX under two-photon irradiation. The latter ORMOSIL nanoparticles can be used as efficient NIR fluorescent contrast agents for various types in vivo animal imaging. We applied IR-820 doped ORMOSIL nanoparticles in in vivo brain imaging of mice. We also demonstrated the applications of them to sentinel lymph node (SLN) mapping of mice. Finally, we showed that the nanoprobes could target the subcutaneously xenografted tumor of a mouse for long time observations. ORMOSIL nanoparticles have great potentials for disease diagnosis and clinical therapies., (Copyright © 2012 Elsevier Ltd. All rights reserved.)