Yan Du,Chunlei Shan,Yuchan You,Minjiang Chen,Luwen Zhu,Gaofeng Shu,Gang Han,Liming Wu,Jiansong Ji,Hong Yu,Yongzhong Du
Lenvatinib (LEN) combined with immune checkpoint PD-1 blockade is among the most effective treatment strategies for advanced hepatocellular carcinoma (HCC) and has been deemed a breakthrough therapy by the Food and Drug Administration. However, this combined strategy is associated with disadvantages such as non-tumor targeted aggregation and low oral bioavailability after long-term administration of LEN, and some patients show poor responses to immunotherapy as well. To overcome these drawbacks, SP94 peptide-modified thermal-sensitive micelles (SP94-poly(ethylene glycol)-poly(acrylamide- co -acrylonitrile, SP94-PEG-p(AAm- co -AN)) with an upper critical solution temperature (UCST) of 43 °C were designed. The micelles were further co-loaded with LEN and IR-1061-Acridine (IR-1061-AcD) to simultaneously achieve small molecule targeted drug, photothermal and photodynamic therapy for HCC under the guidance of near-infrared second-region (NIR-II) fluorescence imaging. After intravenous injection, the co-loaded micelles (SP94-PEG-p(AAm- co -AN)/LEN/IR-1061-AcD, SPLI) showed greater accumulation at tumor sites because SP94 has a high affinity for glucoregulatory protein 78 (GRP78), which is overexpressed on HCC cells. Given these HCC-targeted effects, SPLI appeared useful for NIR-II fluorescence imaging, enabling real-time tumor monitoring and surgical resection. In addition, SPLI could extensively induce immunogenic cell death in tumors, resulting in beneficial systemic immune responses. When further combined with anti-PD-1 immunotherapy, SPLI displayed a superior potential in suppressing tumor growth and metastasis while avoiding immune inhibition. Taken together, our study suggests that the aforementioned combinational strategy could serve as a desired multifunctional approach for HCC management.
Qiaoyun Qi,Yanru Li,Wu Qiu,Wenhai Zhang,Chenyang Shi,Chen Hou,Wen Yan,Jiani Huang,Likun Yang,Hao Wang,Wenxi Guo,Xiang Yang Liu,Naibo Lin
Transient devices have attracted extensive interest because they allow changes in physical form and device function under the control of external stimuli or related commands and have very broad application prospects for information security, biomedical care and the environment. Transient bioelectrical devices were fabricated inspired by a silkworm moth breaking out of its cocoon, which has shown many advantages, including the use of mild stimulation, biocompatible materials, a simple process, and a universal strategy. For the fabrication of the transient devices, heat-sensitive microspheres with a 9.3 mol L−1 LiBr solution in wax shells were prepared by microfluidic technology, which were then assembled into silk fibroin (SF) electronic materials/devices, such as SF conductive film, an LED circuit on SF film, and a Ag/SF film/Pt/SF film memristor. The contribution from the LiBr/wax microspheres to the transient time of the SF films upon exposure to heat was quantitatively investigated. This approach was applied to transiently dissolve a flexible Ag-nanowire resistance circuit line on a SF substrate. Moreover, memristors constructed with a functional layer of SF were destroyed by melting the LiBr/wax microspheres. This technique paves the way for realizing transient bioelectrical devices inspired by biological behavior, which have been well optimized by nature via evolution.
危险品化学品经营许可证（带存储）