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Metabolic syndrome (MetS) includes central obesity, hypertension, insulin resistance, and dyslipidemia and is closely related to nonalcoholic fatty liver disease, atherosclerotic cardiovascular disease (CVD) and type 2 diabetes mellitus, involving multiple causative factors. Current drug therapies for intervention and amelioration of MetS are essential in clinical treatment of metabolic disease. In this report, we proposed an H+-modified montmorillonite (H-MMT) using an acid modification method with ultrafine structure and super absorption ability as a potential drug for MetS. Hamsters fed a high-fat diet were orally treated with H-MMT and simvastatin was applied as a control. H-MMT lowered lipids by decreasing intestinal absorption and promoting lipid excretion, subsequently preventing obesity, fatty liver, and hyperlipidemia. Moreover, H-MMT was significantly safer and better tolerated by the liver compared to simvastatin, which was hepatotoxic. In addition, we found that H-MMT had protective effects on gastric mucosal damage. Therefore, this versatile H-MMT provides a potential strategy to effectively improve MetS and provide gastric mucosal protection in clinical applications.

Metabolic syndrome (MetS) includes central obesity, hypertension, insulin resistance, and dyslipidemia and is closely related to nonalcoholic fatty liver disease, atherosclerotic cardiovascular disease (CVD) and type 2 diabetes mellitus, involving multiple causative factors. Current drug therapies for intervention and amelioration of MetS are essential in clinical treatment of metabolic disease. In this report, we proposed an H

In the context of prodrug nanomedicines for cancer therapy, one of the great challenges is the slow and variable release of the parent drug in tumors. Recently, many smart redox-sensitive nanocarriers have been developed to address this problem. However, due to significant tumor heterogeneity, some redox-sensitive nanomedicines still show poor selectivity in drug release. Herein, we report the design and synthesis of a ROS-triggered prodrug nanoplatform fabricated with oxidation-responsive cabazitaxel (CTX) prodrugs for synergistic chemo-photodynamic therapy, thioether-/selenoether-linked conjugates of CTX and oleic acid (OA). These prodrugs can be readily self-assembled into nanoparticles, with pyropheophorbide a (PPa) co-encapsulated into the prodrug-nanosystem for combination therapy. The dual-source ROS-responsive prodrug nanosystems selectively and rapidly release CTX not only in response to endogenous ROS overproduced in tumor cells, but also to exogenous PPa-generated ROS under laser irradiation. Moreover, the selenium-containing linkage demonstrates significant advantages over a sulfur-containing linkage in terms of ROS-triggered drug release and cytotoxicity. The prepared prodrug-nanosystems significantly prolong the systemic circulation and tumor distribution of both CTX and PPa, thereby demonstrating synergistic chemo-photodynamic therapy in vivo. All these drug delivery advantages render the nanosystem extremely promising for cancer treatment.

Nanoparticles (NPs) are unavoidably covered by a layer of immunogenic proteins upon injection into blood, such as immunoglobins and complements, which buries the active-targeting ligands and triggers the rapid clearance of NPs by the mononuclear phagocytic system. Low antifouling polyethylene glycol is used to inhibit the formation of the immunogenic corona but it leads to poor cellular uptake and the immunogen-related accelerated blood clearance (ABC) phenomenon in multiple administrations. Here, we develop surface maleimide-modified NPs that covalently conjugate in vivo plasma albumin in its corona upon exposure to blood. The in situ recruited low-immunogenic albumin-enriching corona is capable of protecting maleimide-decorated NPs from phagocytosis in the bloodstream, preventing the ABC phenomenon in the second administration, facilitating NP accumulation in the tumor site/cells by the passive EPR effect and albumin receptor-mediated active targeting, and finally improving the antitumor activity. Such findings suggest that the facile strategy, based on the in situ anchored albumin-enriching corona, is efficient at enabling maleimide-decorated NPs to acquire stealth and tumor-targeting ability.

Prodrug self-nanoassemblies have many advantages for anticancer drug delivery, including high drug loading rate, resistance to recrystallization, and on-demand drug release. However, few studies have focused on their protein corona, which is inevitably formed after entering the blood and determines their subsequent fates in vivo. To actively tune the protein corona of prodrug nanoassemblies, three maleimide-paclitaxel prodrugs were synthesized via different redox-sensitive linkers (ester bond, thioether bond and disulfide bond). After incubation with rat plasma, the surface maleimide groups effectively captured albumins, resulting in albumin-enriched protein corona. The recruited albumin corona enabled enhanced tumor accumulation and facilitated cellular uptake, ensuring the high-efficiency delivery of nanoassemblies to tumor cells. Surprisingly, we found that the traditionally reduction-sensitive disulfide bond could also be triggered by reactive oxygen species (ROS). Such a redox dual-responsive drug release property of the disulfide bond-containing prodrug nanoassemblies further increased the selectivity in cytotoxicity between normal and tumor cells. Moreover, the disulfide bond-containing prodrug nanoassemblies exhibited the highest antitumor efficacy in vivo compared to marketed Abraxane® and other prodrug nanoassemblies. Thus, the fabrication of the maleimide-decorated disulfide bond bridged prodrug nanoassembly, integrating a tunable protein corona and on-demand drug release, is a promising strategy for improved cancer chemotherapy.