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A theranostic agent for cancer therapy and imaging in the second near-infrared window.

ABSTRACT: Theranostic nanoparticles are integrated systems useful for simultaneous diagnosis and imaging guided delivery of therapeutic drugs, with wide ranging potential applications in the clinic. Here we developed a theranostic nanoparticle (~ 24 nm size by dynamic light scattering) p-FE-PTX-FA based on polymeric micelle encapsulating an organic dye (FE) fluorescing in the 1,000-1,700 nm second near-infrared (NIR-II) window and an anti-cancer drug paclitaxel. Folic acid (FA) was conjugated to the nanoparticles to afford specific binding to molecular folate receptors on murine breast cancer 4T1 tumor cells. In vivo, the nanoparticles accumulated in 4T1 tumor through both passive and active targeting effect. Under an 808 nm laser excitation, fluorescence detection above 1,300 nm afforded a large Stokes shift, allowing targeted molecular imaging tumor with high signal to background ratios, reaching a high tumor to normal tissue signal ratio (T/NT) of (20.0 ± 2.3). Further, 4T1 tumors on mice were completed eradicated by paclitaxel released from p-FE-PTA-FA within 20 days of the first injection. Pharmacokinetics and histology studies indicated p-FE-PTX-FA had no obvious toxic side effects to major organs. This represented the first NIR-II theranostic agent developed.

SUBMITTER: Ma Z

PROVIDER: S-EPMC6907162 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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A theranostic agent for cancer therapy and imaging in the second near-infrared window.

Ma Zhuoran Z Wan Hao H Wang Weizhi W Zhang Xiaodong X Uno Takaaki T Yang Qianglai Q Yue Jingying J Gao Hongpeng H Zhong Yeteng Y Tian Ye Y Sun Qinchao Q Liang Yongye Y Dai Hongjie H

Nano research 20180929

Theranostic nanoparticles are integrated systems useful for simultaneous diagnosis and imaging guided delivery of therapeutic drugs, with wide ranging potential applications in the clinic. Here we developed a theranostic nanoparticle (~ 24 nm size by dynamic light scattering) p-FE-PTX-FA based on polymeric micelle encapsulating an organic dye (FE) fluorescing in the 1,000-1,700 nm second near-infrared (NIR-II) window and an anti-cancer drug paclitaxel. Folic acid (FA) was conjugated to the nanop ...[more]

PMID: 31832124

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Project description:The therapeutic efficacy of fluorescence image-guided tumor surgery and photodynamic therapy (PDT) is impaired by the penetration depth limitation, low signal-to-noise ratio of traditional first near-infrared window (NIR I) fluorescence and the hypoxic tumor microenvironment. Here, a "red blood cell-based multimodal probe" was proposed to achieve enhanced tumor targeting and retention of fluorescent probes after an intravenous injection, so that second near-infrared window (NIR II) fluorescence bioimaging-guided complete tumor resection and high-efficiency photodynamic therapy could then be realized. Methods: The hexanoic acid ester-modified rose bengal (RB-HA), RGD (Arginine-Glycine-Aspartic) peptide and avidin were covalently coupled onto amine-modified upconversion nanoparticles (UCNPs) via EDC/NHS reaction (UCNPs@RB@RGD@avidin). Afterwards, the complex of ICG with bovine serum albumin (BSA) was loaded into RBCs through hypotonic dialysis (RBC@ICG). Then, the membrane proteins of RBC@ICG were biotinylated by biotin-modified phospholipids (RBC@ICG@biotin). Finally, the RBCp (Red Blood Cell based probe) was obtained by crosslinking UCNPs@RB@RGD@avidin to RBC@ICG@biotin through the interaction of avidin and biotin. The obtained multimodal RBCp was extensively characterized, both in vitro and in vivo, including analysis of chemical, physical and fluorescent features, O2 delivery ability, tumor accumulation, NIR II fluorescence bioimaging ability, photodynamic therapeutic efficiency, and biosafety. Results: The RBCp experienced efficient tumor targeting and long tumor retention for almost 4 h after intravenous injection, and the superior signal-to-noise ratio at the optimal time window can be used for guiding precise tumor resection under an 808-nm laser irradiation to facilitate lymph popliteal metastasis surgical delineation. Meanwhile, the RBCp can provide laser-responsive O2 release to enhance the PDT efficiency of popliteal lymph node metastasis under NIR II fluorescence bioimaging guidance. These excellent performances obviously lead to remarkably enhanced synergistic therapeutic effects of tumor surgery and metastatic inhibition. Conclusion: The proposed strategy will develop a new platform to increase surgical resection completeness and improve PDT efficiency, resulting in the successful and complete inhibition of tumor and metastasis, which could offer a promising approach for the clinical translation of malignant tumor treatment.

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A theranostic agent for cancer therapy and imaging in the second near-infrared window.

Publications

A theranostic agent for cancer therapy and imaging in the second near-infrared window.

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