Integrating biomedical imaging and multimodal therapies into one platform for enhanced anticancer efficacy is of great significance. Herein, a core/shell structured nanotheranostic (CuS@copolymer) for magnetic resonance imaging (MRI)-guided chemo-photothermal therapy was simply prepared via emulsifier-free emulsion polymerization with the full participation of hydrophilic CuS NPs, styrene (St), N-isopropylacrylamide (NIPAm), methacrylic acid (MAA), and polymerizable rare earth complex (Gd­(AA)3phen). The synthesized multifunctional microspheres with excellent biocompatibility exhibited high loading capacity (15.3 wt %) for DOX·HCl and excellent drug release under low pH and high temperature. The photosensitive CuS cores which can simultaneously efficiently absorb near-infrared (NIR) light and convert NIR light to fatal heat, leading to a synergistic therapeutic effect combined photothermal therapy (PTT) with chemotherapy. Moreover, the temperature sensitive copolymer attached onto the CuS nanoparticles was able to be productively infected by the thermal effect and give rise to a highly controllable DOX release. Furthermore, the CuS@copolymer/DOX showed an enhanced therapeutic efficacy against 4T1 cells than separate photothermal therapy or chemotherapy. Additionally, the drug delivery procedure could be visualized by in vivo MR images and the longitudinal relaxivity (r 1) was calculated to be 10.72 mM–1 s–1. These results suggest the CuS@copolymer microspheres highly attractive candidates for biomedical applications.

Background Icotinib has been widely used in patients with non-small cell lung cancer (NSCLC), and have significantly enhanced the overall survival rate of NSCLC patients. However, acquired drug resistance limits its clinical efficacy. Tumor cell-derived exosomes have been reported to participate in various biological processes, including tumor invasion, metastasis and drug resistance. Materials and methods In the present study, drug resistance was measured by MTT assay. Exosomes were extracted from the cell supernatant using ultracentrifugation and identified by exosomal marker. HCC827 cells were treated with exosomes derived from icotinib-resistant (IR) HCC827 to observe the invasion and migration of parent cells. The expression of exo-mRNA was analyzed by reverse transcription-quantitative polymerase chain reaction (RT-PCR). In addition, 10 exo-mRNAs detecting from the plasma and bronchoalveolar lavage fluid (BALF) of NSCLC patients with icotinib treatment were used to establish a new drug resistant-warning formula. Results The oncogene MET into exosomes was identified from icotinib-resistant lung cancer cells, and this was also presented in exosomes in NSCLC patients diagnosed with cancer metastasis after icotinib treatment. The knockdown of MET in exosomes significantly decreased the ability of invasion and migration in HCC827 cells. Conclusion It was suggested that MET might be specifically package and transferred by exosomes to modify the invasion and migration ability of the surrounding icotinib-sensitive cells.

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