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Sensitivity and specificity of molecular probes are two important factors in determining the accuracy of cancer diagnosis or the efficacy of cancer treatment. However, the development of probes with high sensitivity and strong specificity still poses many challenges. Herein, we report an 18F-labeled smart tracer ([18F]1) targeting cancer-associated biotin receptor (BR) and self-assembling into nanoparticles in response to intracellular glutathione. The tracer [18F]1 selectively targeted BR-positive cancer cells A549 and Hela and formed nanoparticles through self-assembly with an average diameter of 138.2 ± 16.3 nm. The character of self-assembly into nanoparticles enhanced the uptake and extended the retention of probe [18F]1 in the target tissue and hence improved the quality of positron emission tomography (PET) images. Thus, [18F]1 is a promising PET tracer for accurately detecting BR-positive cancers. Moreover, the tumor microenvironment responsive “head-to-foot” self-assembly nanoplatform is particularly attractive for development of other smart molecular probes.

Background: Lung cancer is the leading cause of cancer-associated mortality in the world. Traditional cancer therapies prolong life expectancy of patients but often suffer from adverse reactions. Photodynamic therapy (PDT) has been recommended as a treatment option for lung cancer in several countries, due to its non-invasive procedures, high selectivity and weak side effects. Objective: We have designed and synthesized a biotin receptor-targeted silicon phthalocyanine (IV) (compound 1) which showed good therapeutic effect on biotin receptor-positive tumors. Since the overexpression of biotin receptor (BR) is also present in human lung cancer cells (A549), we explored the therapeutic properties of compound 1 on A549 xenograft tumor models. Method: The selectivity of compound 1 toward A549 cells was studied with fluorescence microscope and IVIS Spectrum Imaging System. The cytotoxicity was measured using MTT assay. In vivo anti-tumor activity was investigated on the nude mice bearing A549 xenografts. Results: In vitro assays proved that compound 1 could selectively accumulate in A549 cells via the BR-mediated internalization. In vivo imaging and distribution experiments showed that compound 1 could selectively accumulate in tumor tissues of tumor-bearing mice. After 16 days of the treatment, the volumes of tumor in PDT group were obviously smaller than that in other groups. Conclusion: This study demonstrates that compound 1 is a promising photosensitizer and has broad application prospects in clinical PDT of lung cancers.

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