Cinobufagin is used as a traditional Chinese medicine for cancer therapy. However, it has some disadvantages, such as poor water solubility, short circulating half-life, and low bioavailability. In the present study, a targeted delivery and smart responsive polydopamine (PDA)-based nanomedicine for delivering cinobufagin was rationally designed to improve the anticancer efficacy of the compound for the treatment of lung cancer. The modification of the nanomedicine using folic acid first mediated tumor targeting via the interaction between folic acid and its receptors on tumor cells. After lysosomes escape, the PDA nanomedicine was triggered by the low pH and released its cargo into the tumor microenvironment. The nanomedicine had a better therapeutic effect against lung cancer when used in combination with photothermal therapy. Compared with other nanomedicines used with photothermal therapy, this nanocarrier was not only sensitive to biologically low pH levels for on-demand drug release, but was also biodegradable, breaking down into biocompatible terminal products. Therefore, the proposed drug delivery system with targeted delivery and smart release demonstrated potential as a multifunctional nanoplatform that can enhance the bioavailability and reduce the side effects of chemotherapeutic agents.

Feiyanning (FYN), the Chinese herbal medicine (CHM), has been used to manage non-small cell lung cancer (NSCLC) for the past 23 years. Chemotherapeutic drugs can induce autophagy in cancer cells to protect themselves from death. However, FYN can inhibit the protective autophagy in cancer cells. We investigated the biological mechanisms on the synergistic effects of FYN combined with chemotherapy in lung cancer cells. We analyzed the effective chemical components for the quality control of FYN using the UPLC-Q-TOF-MS.The cell proliferation ability was detected by the cell counting kit-8 (CCK-8) and colony formation. The cell apoptosis was determined with Flow cytometry. Expression of important differential proteins were detected by western blot. Autophagy structure was observed by TEM (Tansmission electron microscopy). Tandem mCherry-EGFP-LC3B immunofluorescence was used to measure autophagic flux. Both FYN and cisplatin significantly induced apoptosis and inhibited cell proliferation in A549 cells. FYN reduced cell viability and increased apoptotic cell populations less effectively than cisplatin. FYN cooperated with cisplatin suppressed the cell viability, colony formation, as well as increased the cell apoptosis rate, and the expression of cleaved caspase-3 and PARP. FYN inhibited autophagy in A549 cells, which characterized by the decrease of autophagosome formation, lysosomal fusion, LC3B-II accumulation and SQSTM1 degradation, down-regulation of ATG5 and ATG7. Protective autophagy in A549 cells was induced by cisplatin. Suppression of the autophagic response using chloroquine (CQ) which is autophagy inhibitor improved the ability of cisplatin to kill cancer cells, as did FYN combined with cisplatin. In summary, we revealed that the synergistic mechanism of FYN and cisplatin is that FYN inhibited the protective autophagy induced by cisplatin in A549 cells.