Photothermal therapy (PTT) has been developed as a useful therapeutic method for cancer treatment. Localization of PTT agents in cancer sites and targeting capacity are required to further increase therapeutic efficacy. In this study, gold nanoparticles (AuNPs) and gelatin were functionalized with folic acid (FA) and hybridized to prepare FA-functionalized gelatin–AuNPs composite scaffolds. AuNPs with rod and star shapes of three sizes (40, 70, and 110 nm) were used for the hybridization to investigate the influence of AuNPs shape and size. The composite scaffolds showed porous structures with good interconnectivity. Modification with FA increased capture capacity of the composite scaffolds. Hybridization with AuNPs rendered the composite scaffold a good photothermal conversion property under near-infrared (NIR) laser irradiation. Temperature change during laser irradiation increased with the laser power intensity and irradiation time. The shape and size of AuNPs also affected their photothermal conversion property. The composite scaffold of gold nanorods 70 (FA-G/R70) had the highest photothermal conversion capacity. Breast cancer cells cultured in the FA-G/R70 composite scaffold were killed under NIR laser irradiation. Mouse subcutaneous implantation further demonstrated the excellent photothermal ablation capability of FA-G/R70 composite scaffold to breast cancer cells. The FA-functionalized composite scaffolds were demonstrated a high potential for local PPT of breast cancer.
Multidrug resistance (MDR) is one of the major reasons for the clinical failure of cancer chemotherapy. Autophagy activation serves a crucial role in MDR. However, the specific molecular mechanism linking autophagy with MDR remains unknown. The results of the present study demonstrated that autophagy was inhibited and microRNA (miR)-199a-5p levels were upregulated in MDR model lung cancer cells (A549/T and H1299/T) compared with those in the parental cell lines. Paclitaxel (PTX) treatment increased the expression levels of miR-199a-5p in parental lung cancer cells compared with those in PTX-untreated cells, and these expression levels were negatively correlated with PTX sensitivity of the cells. miR-199a-5p knockdown in A549/T cells induced autophagy and resensitized cells to multiple chemotherapeutic drugs including PTX, taxotere, topotecan, SN38, oxaliplatin and vinorelbine. By contrast, miR-199a-5p overexpression in A549 cells suppressed autophagy and desensitized cells to these chemotherapeutic drugs. Mechanistically, the results of the present study demonstrated that miR-199a-5p blocked autophagy by activating the PI3K/Akt/mTOR signaling pathway and inhibiting the protein expression of autophagy-related 5. Furthermore, p62 protein was identified as a direct target of miR-199a-5p; miR-199a-5p bound to p62 mRNA to decrease its mRNA and protein expression levels. In conclusion, the results of the present study suggested that miR-199a-5p may contribute to MDR development in lung cancer cells by inhibiting autophagy and targeting p62. The regulatory effect of miR-199a-5p on autophagy may provide novel insights for future multidrug-resistant lung cancer chemotherapy.
In recent years, the synergistic effect of photothermal therapy (PTT) and chemotherapy has been recognized as an effective strategy for cancer treatment. Controlling the PTT temperature and drug release profile...
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