Shuangquan Gou,Gangyang Wang,Yanan Zou,Wenbo Geng,Tingting He,Zizhen Qin,Lingbin Che,Qian Feng,Kaiyong Cai
Developing a drug delivery platform that possesses universal drug loading capacity to meet various requirements of cancer treatment is a challenging yet interesting task. Herein, a self-assembled gelatin/silk fibroin composite (GSC) particle based drug delivery system is developed via microphase separation followed by desolvation process. Thanks to its preassembled microphase stage, this GSC system is suitable for varying types of drugs. The desolvation process fix drugs inside GSC rapidly and densify the GSC structure, thereby achieving efficient drug loading and providing comprehensive protection for loaded drugs. Actually, the size of this brand-new non-pore dependent drug delivery system can be easily adjusted from 100 nm to 20 µm to fit different scenarios. This work selects GSC with 3 µm diameter as the universal inhaled drug delivery platform, which shows an excellent transmucosal penetration and lung retention ability. Additionally, the MMP-9 sensitive degradation property of GSC enhances the targeted efficiency of drugs and reduces side effects. Intestinally, GSC can self-amplify the regulation of innate immunity to reverse the cancerous microenvironment into an antitumor niche, significantly improving the therapeutic effect of drugs. This study of GSC universal drug platform provides a new direction to develop the next-generation of drug delivery system for lung cancer.
Yu Zhang,Wu Yang,Wei Xiong,Yu Chen,Pengzhen Zhuang,Haoran Wang,Diana M. Toivola,Yawei Du,Hongbo Zhang,Wenguo Cui
The positive feedback circuit between the complement system and inflammatory immune responses maps the malignant progression of chronic joint inflammation. Prolonged dysregulation of the immune microenvironment in rheumatoid arthritis (RA) further exacerbates sustained complement activation, thereby establishing a vicious cycle. In this study, MMP-9-responsive, injectable micro-nano geneplexes (C5ASO@HAP-CL-TIMP@HMs) are developed for on-demand regulation of complement component C5, aiming to disrupt this pathological circuit. C5 antisense oligonucleotides (C5ASO) are loaded into cationic liposomes, which are subsequently encapsulated within hyaluronic acid microspheres via click chemistry. In vitro, these geneplexes effectively block abnormal C5 activation in RA synoviocytes, restore macrophage polarization balance, reduce pro-inflammatory cytokine levels and immune complex precursor molecules, and upregulate anti-inflammatory mediators. In an adjuvant-induced arthritis rat model, they significantly alleviate joint swelling and cartilage degradation and suppress inflammatory responses, further highlighting the therapeutic potential of geneplexes in dismantling the complement-inflammation circuit. In summary, the development of micro-nano geneplexes capable of precisely disrupting the complement-inflammatory circuit in RA offers a promising new perspective for the targeted treatment of chronic joint inflammation.
危险品化学品经营许可证（带存储）