Endogenous stimuli-responsive drug delivery nanoplatforms for kidney disease therapy.

Kidney disease is one of the most life-threatening health problems, affecting millions of people in the world. Commonly used steroids and immunosuppressants often fall exceptionally short of outcomes with inescapable systemic toxicity. With the booming research in nanobiotechnology, stimuli-responsive nanoplatform has come an appealing therapeutic strategy for kidney disease. Endogenous stimuli-responsive materials have shown profuse promise owing to their enhanced spatiotemporal control and precise to the location of the lesion. This review focuses on recent advances stimuli-responsive drug delivery nano-architectonics for kidney disease. First, a brief introduction of pathogenesis of kidney disease and pathological microenvironment were provided. Then, various endogenous stimulus involved in drug delivery nanoplatforms including pH, ROS, enzymes, and glucose were categorized based on the pathological mechanisms of kidney disease. Next, we separately summarized literature examples of endogenous stimuli-responsive nanomaterials, and outlined the design strategies and response mechanisms. Finally, the paper was concluded by discussing remaining challenges and future perspectives of endogenous stimuli-responsive drug delivery nanoplatform for expediting the speed of development and clinical applications.

Targeting of non-apoptotic cancer cell death mechanisms by quercetin: Implications in cancer therapy.

The ultimate goal of cancer treatment is to kill cancer cells, based on the use of various therapeutic agents, such as chemotherapy, radiotherapy, or targeted therapy drugs. Most drugs exert their therapeutic effects on cancer by targeting apoptosis. However, alterations in apoptosis-related molecules and thus assisting cells to evade death, eventually lead to tumor cell resistance to therapeutic drugs. The increased incidence of non-apoptotic cell death modes such as induced autophagy, mitotic catastrophe, senescence, and necrosis is beneficial to overcoming multidrug resistance mediated by apoptosis resistance in tumor cells. Therefore, investigating the function and mechanism of drug-induced non-apoptotic cell death modes has positive implications for the development of new anti-cancer drugs and therapeutic strategies. Phytochemicals show strong potential as an alternative or complementary medicine for alleviating various types of cancer. Quercetin is a flavonoid compound widely found in the daily diet that demonstrates a significant role in inhibiting numerous human cancers. In addition to direct pro-tumor cell apoptosis, both in vivo and in vitro experiments have shown that quercetin exerts anti-tumor properties by triggering diverse non-apoptotic cell death modes. This review summarized the current status of research on the molecular mechanisms and targets through which quercetin-mediated non-apoptotic mode of cancer cell death, including autophagic cell death, senescence, mitotic catastrophe, ferroptosis, necroptosis, etc.

Hesperetin, a Promising Treatment Option for Diabetes and Related Complications: A Literature Review.

The morbidity and mortality of diabetes have increased dramatically in recent decades. Novel strategies for treating diabetes and its complications with minimal side effects are in urgent need. New monomeric molecules extracted from herbal medicine, which is a form of alternative medicine, are being sought as drug candidates for the treatment of diabetes and its complications. Hesperetin (Hst), a citrus flavonoid, is of increasing interest in scientific studies recently due to its properties in combating diabetes and its complications, whereas existing studies are scattered and unsystematic. Here, we summarized the literature studies over the last 10 years to review the potential therapeutic role of Hst in the prevention and mitigation of diabetes and its complications, intending to provide promising strategies for the clinical management of diabetes and its complications.

A New Ratiometric Fluorescent Probe for Specific Monitoring of hROS under Physiological Conditions Using Boric Acid-Protected l-DOPA Gold Nanoclusters.

The specific monitoring of physiological highly reactive oxygen species (hROS) using fluorescent gold nanoclusters (AuNCs) remains a challenge for scientists. Herein, SLB-AuNC was first synthesized via an ecofriendly one-pot method using starch as a template, l-3,4-dihydroxyphenylalanine (l-DOPA) as a reducing and a capping agent, and boric acid as a protecting agent for the catechol moiety of l-DOPA. The ingenious introduction of starch and boric acid enhanced the dispersibility, quantum yield, and photostability of fluorescent SLB-AuNCs. The obtained SLB-AuNCs possessed good monodispersity with an average diameter of 2.9 ± 0.8 nm and exhibited highly stable fluorescence with maximum emission at 480 nm under physiological conditions. A ratiometric fluorescent probe for hROS was developed through an oxidization-regulated Förster-resonance-energy-transfer process between SLB-AuNCs and 2,3-diaminophenazine (the oxidative product of hROS and o-phenylenediamine, with maximum fluorescence emission at 560 nm). With increasing amount of hROS, the outstanding fluorescence variation of the probe (I560 nm/I480 nm) enhanced about 300-fold, accompanied with a distinguishable color change from cyan to yellow. The detection limits of •OH, ClO-, and ONOO- were calculated as 0.11, 0.50, and 0.69 µM, respectively. High selectivity was achieved using o-phenylenediamine as a specific signal response for hROS to enable no interference reaction of other ROS toward SLB-AuNCs. The practicability of the proposed probe with super biocompatibility was evaluated by measuring exogenous and endogenous hROS levels in HeLa cells through fluorescence imaging. This work provides a novel strategy to design fluorescent AuNC probes for physiological hROS with great potential for the application of bioassay and bioimaging.

A pH-Controlled Kit for Total and Direct Bilirubin Built on Mimetic Peroxidase CoFe2O4-DOPA-Catalyzed Fluorescence Enhancement.

Facile and reliable detection of total bilirubin (Bt, summation of indirect and direct bilirubin) and direct bilirubin (Bd) in human serum is of crucial importance to clinical diagnosis. However, it is still a challenge to explore an ideal recognition system for discriminating Bd and indirect bilirubin (Bi). In this work, a dual-functional sensor for Bt and Bd was first built on pH-controlled and mimetic peroxidase-catalyzed fluorescence enhancement. The fluorescence of nitrogen-doped graphene quantum dots (NGQDs) can be effectively quenched by bilirubin through the IFE process. With the catalysis of dopamine-derived magnetic ferrite nanoparticles (CoFe2O4-DOPA), both Bd and Bi were oxidized by H2O2 to colorless and fluorescent oxidates at pH 8.0. Interestingly, only Bd was oxidized at pH 3.5. The discriminating principle of Bd and Bi relied on their pH-controlled oxidation potentials. A sensitive sensor for Bt and Bd was developed on the enhanced fluorescence of the NGQDs/CoFe2O4-DOPA/H2O2 sensing system after bilirubin oxidation, which was originated from a combination of the fluorescence recovery of NGQDs and newly spawned fluorescence of bilirubin oxidates. The designed probe well quantifies Bt and Bd with the detection limits of 10 and 50 nM, respectively. Moreover, a portable diagnostic kit was fabricated and successfully used for the detection of Bt and Bd in 60 unrelated human serum samples, and the obtained results were almost consistent with those measured by biochemistry analyzer. The present kit exhibits the superiorities of high sensitivity and stability, interference-resistant, and green reagents, making it a promising candidate for bilirubin detection in the clinical diagnosis of jaundice.