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Nanobodies have been developed rapidly as targeted probes for molecular imaging owing to their high affinity, outstanding tissue penetration, and rapid blood clearance. However, the short retention time at the tumor site limits their application in targeted radionuclide therapy. In this study, we designed a dual-targeting nanobody referred to as MIRC213-709, which can specifically bind to the HER2 receptor in tumor cell lines with high affinity (by nanobody MIRC213) and endogenous IgG in plasma to prolong the half-life by the MIRC213 C-terminal fusion nanobody, MIRC709. The nanobodies were site-specifically radiolabeled with

The limited efficacy of radiotherapy leads to radio-resistance and high rates of tumor recurrence and metastasis, which is caused by tumor hypoxia, rapid DNA damage repair, and especially the suppressive immune microenvironment of tumor. Lots of immune cell-derived exosomes can regulate antitumor immunity, but their application in enhancing radiotherapy is rarely studied. Herein, as a model of concept, M1 macrophage-derived exosomes (M1Exos) is engineered as effective radiotherapy sensitizers, realizing the trilogy of radiotherapy sensitization: 1) M1Exos is engineered to express catalases on the inside of membrane, which can effectively relieve tumor hypoxia, and enhance DNA damage. 2) The DNA damage repair inhibitor is loaded in M1Exos to effectively inhibit DNA damage repair. 3) M1Exos can polarize M2 macrophages into M1 phenotypes, and the anti-PD-L1 nanobody engineered on the outside of M1Exos can relieve the immunosuppression of T cells, both ultimately leading to the remodeling of the tumor suppressive microenvironment. The trilogy of radiotherapy sensitization achieves excellent antitumor efficacy, exhibiting the good utility of engineering immune cell-derived exosomes as radiotherapy sensitizers, inspiring the future efforts to explore different kinds of immune cell-derived exosomes for enhanced radiotherapy.

HER2 receptor-specific monoclonal-antibody-templated gold nanoclusters, Herceptin-templated Au NCs (Her-Au NCs), have been successfully obtained via "green" synthesis. This strategy allows the fluorescent gold nanoclusters (Au NCs) formed in the three-dimensional structure of Herceptin without destroying the high specificity and affinity to HER2 receptors. The Her-Au NCs have been found to be superior compared to Cy3-Herceptin in the fluorescence emission (λ

Doxorubicin (DOX) has been clinically used as a broad-spectrum chemotherapeutic agent for decades, but its clinical application is hindered by the lack of tumour specificity, severe cardiotoxicity and haematotoxicity. Pre-targeted strategies are highly tumour-specific, therapeutic approaches. Herein, a novel pre-targeted system was constructed, aiming to enhance anticancer efficacy of DOX and maximally reduce its side effects. Methods: The DOX prodrug (bDOX) was first synthesized by conjugating DOX with mini-PEGylated (mPEGylated) biotin through a pH-sensitive bond. During the pre-targeted treatment, avidin was first administrated. After an optimized interval, bDOX was second administrated. The nontoxic prodrug bDOX was eventually transformed into the toxic anticancer form (DOX) by a pH-triggered cleavage specifically in tumour cells. The drug efficacy and side effect of the two-step, pre-targeted treatment were fully compared with free DOX in vitro and in vivo. Results: The prodrug bDOX was quite stable under neutral conditions and nearly nontoxic, but was immediately transformed into the toxic anticancer form (DOX) under acidic conditions. Compared to free DOX, the pre-targeted bDOX exhibited a higher cellular uptake by human colorectal tumour cells (LS180 and HT-29 cells). In vivo evaluation performed on LS180 xenograft animal model demonstrated that the pre-targeted bDOX achieved a much more significant tumour inhibition than free DOX. The largely decreased, unwanted bystander toxicity was demonstrated by changes in body weight, cardiomyocyte apoptosis, blood routine examination and splenic pathological changes. Conclusion: The high therapeutic efficacy, together with the minimal side effects, of this easily synthesized, pre-targeted system exhibited immense potentiality for the clinical application of DOX delivery.

An efficient chemical reduction protocol has been developed for the synthesis of hyaluronic acid-coated silver nanoparticles (HA-Ag NPs) that are spherical, ultrasmall and monodisperse. The as-synthesized HA-Ag NPs not only exhibited excellent long-term stability and low cytotoxicity but also could be used as a nanoplatform for X-ray computed tomography (CT) and single-photon emission computed tomography (SPECT) imaging after being radiolabeled with 99mTc.

Despite the good prognosis of the low-risk thyroid cancer, there are no truly effective treatments for radioactive iodine-refractory thyroid cancer. Herein, a novel theranostic nanoplatform, as well as a smart doxorubucin (DOX) delivery system is fabricated. Gelatin-stabilized polypyrrole nanoparticles are reported for the first time. The combination of gelatin-stabilized polypyrrole and cyclodextrin-DOX complexes enabling three-stimuli-controlled drug delivery, including the enzyme-sensitive, pH-sensitive and photothermal-sensitive drug release, exhibiting a new way to equip photothermal agents with precisely controlled drug delivery. Anti-galectin-3 antibodies are utilized as the targeting molecules of nanoparticles in the first time, which surprisingly increase intracellular DOX uptake by enhanced clathrin-mediated endocytosis, showing galectin-3 can be employed as a highly efficient target of drug delivery systems. The nanoparticles achieve excellent photoacoustic imaging effect, enabled chemo-photothermal combined therapy with pinpointed drug delivery. Compared to free DOX, these multifunctional nanoparticles decrease the heart damage, but greatly increase the tumor/heart ratio of DOX concentration by 12.9-fold. The tumors are completely eradicated without any recurrence after the in vivo combined therapy. To the best of the authors' knowledge, this is also the first report to apply photoacoustic imaging-guided chemo-photothermal therapy for thyroid cancer, showing great potential to solve the dilemma in thyroid cancer therapy.