Jiahui Yu

Background and Objective: Pancreatic ductal adenocarcinoma (PDAC) is characterized by dense extracellular matrix (ECM) with overexpression of extra domain B fibronectin (EDB-FN). Methods: Herein, we investigated novel albumin-binding peptide–drug conjugates, Mc-ZD2-SN38 and SSC-ZD2-SN38, which integrate the prolonged circulation properties of albumin with the active targeting capability of the ZD2 peptide toward EDB-FN. Covalent and noncovalent albumin-binding strategies extended the half-life by approximately 100-fold and 15-fold, respectively, compared with the non-albumin-binding peptide–drug conjugate (PDC) (ZD2-SN38). Results: Notably, ZD2-mediated targeting markedly reduced payload accumulation in major organs, resulting in an improved safety profile. In a BxPC-3 xenograft model, Mc-ZD2-SN38 and SSC-ZD2-SN38 demonstrated potent and sustained antitumor efficacy. Conclusions: These findings establish a long circulation and active targeting drug delivery strategy, providing an ideal framework for the development of PDCs with enhanced therapeutic indices.

Albumin-binding prodrugs have been explored to overcome the limitations of small-molecule anticancer chemotherapy agents, such as inadequate physiological and pharmaceutical compatibility, as well as rapid renal clearance. Herein, we investigated two endogenous albumin-binding prodrugs, M-g-SN38 and S-g-SN38, forming macromolecular conjugates. Both prodrugs exhibited robust stability in murine and human plasma, crucial for their therapeutic potential. Selective activation by β-glucuronidase ensures minimal toxicity in their inactive state. Notably, M-g-SN38 exhibited higher cellular uptake, a longer circulation half-life, and enhanced tumor accumulation compared to S-g-SN38, suggesting its greater potential for improved antitumor efficacy. In vivo, M-g-SN38 exhibited significant antitumor activity, leading to profound tumor reduction and, in many cases, marked depletion and complete eradication in all treated mice in the HCT116 xenograft model. Furthermore, M-g-SN38 also demonstrated pronounced antitumor efficacy in the BxPC-3 xenograft model. Together, these findings provide new insights for the development of albumin-binding prodrugs.

Lipid nanoparticles (LNPs) are widely used for nucleic acid delivery but face challenges like limited targeting and accelerated blood clearance (ABC) effect. We design three ionizable oligomers (IOs) that, with polylactide-polyethylene glycol (PLA-PEG), form a potential siRNA delivery system, named Ionizable Polymeric Micelles (IPMs). The siRNA encapsulated IPMs escape from lysosomes upon cellular uptake, and silence the target gene. A fibroblast activation protein inhibitor modified IPMs (FAPi-IPMs) show higher targeting for activated hepatic stellate cells (HSCs) compared to that for hepatocytes, silencing both HSP47 and HMGB1, reducing collagen secretion and liver inflammation, thereby treating fibrosis. Moreover, IPMs and FAPi-IPMs mitigate ABC effect and produce fewer PEG antibodies than LNPs, and show minimal apolipoprotein adsorption in vivo compared with LNPs, differentiating their targeting effects from LNPs. In conclusion, IPMs represent a nucleic acid delivery system with alternative targeting ability and reduced ABC effect.

This work proposes anin situpermeation method that can enable the self-adaptive adhesion of hydrogel biosensors on various surfaces.

This paper intends to solve the robust consensus problem of cyber-phycial networks with signed graph under cyber-attacks. The conmunication topology is considered to be directed. First, A fully distributed robust control protocol is presented without uasage of any glabol information, when actuator suffered false dada input attacks. Next, the stalibity is proved by Lyapounov Theory. Finally, a simulation to verify the main result in this paper.

In order to solve the problem that the traditional moving target tracking algorithm is vulnerable to interference and difficult to accurately track the target for a long time, we first introduce the common target tracking algorithm under the dynamic background, and then we determine the KCF algorithm which has better tracking effect and real-time performance. Then, aiming at the problem of target box offset in the longtime tracking, a tracking algorithm combining Kalman filter algorithm and KCF algorithm is proposed. Finally, the actual effect proves to be effective.