Brain ischemia/reperfusion (I/R) injury (BI/RI) is a leading cause of death and disability worldwide. However, the outcome of pharmacotherapy for BI/RI remains unsatisfactory. Innovative approaches for enhancing drug sensitivity and recovering neuronal activity in BI/RI treatment are urgently needed. The purpose of this study was to evaluate the protective effects of tumor necrosis factor (TNF)-α-loaded poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(l-lysine)) (TNF-α/PEG-b-(PELG-g-PLL)) nanoparticles on BI/RI. The particle size of PEG-b-(PELG-g-PLL) and the loading and release rates of TNF-α were determined. The nanoparticle cytotoxicity was evaluated in vitro using rat cortical neurons. Sprague Dawley rats were preconditioned with free TNF-α or TNF-α/PEG-b-(PELG-g-PLL) polyplexes and then subjected to 2 hours ischemia and 22 hours reperfusion. Brain edema was assessed using the brain edema ratio, and the antioxidative activity was assessed by measuring the superoxide dismutase (SOD) activity and the malondialdehyde (MDA) content in the brain tissue. We further estimated the inflammatory activity and apoptosis level by determining the levels of interleukin-4 (IL-4), IL-6, IL-8, IL-10, and nitric oxide (NO), as well as the expression of glial fibrillary acidic protein (GFAP), intercellular adhesion molecule-1 (ICAM-1), and cysteine aspartase-3 (caspase-3), in the brain tissue. We provide evidence that TNF-α preconditioning attenuated the oxidative stress injury, the inflammatory activity, and the apoptosis level in I/R-induced cerebral injury, while the application of block copolymer PEG-b-(PELG-g-PLL) as a potential TNF-α nanocarrier with sustained release significantly enhanced the bioavailability of TNF-α. We propose that the block copolymer PEG-b-(PELG-g-PLL) may function as a potent nanocarrier for augmenting BI/RI pharmacotherapy, with unprecedented clinical benefits. Further studies are needed to better clarify the underlying mechanisms.

Cancer is a serious threat to human health, and chemotherapy for cancer is limited by severe side effects. Curcumin (CUR) is a commonly used natural product for antitumor treatment without safety concerns. However, low bioavailability and poor tumor accumulation are great obstacles for its clinical application. Our previous research has demonstrated that platelet membrane-camouflaged nanoparticles can efficiently ameliorate the in vivo kinetic characteristics and enhance the tumor affinity of payloads. Nevertheless, the antitumor efficiency of this formulation still needs to be thoroughly investigated, and its drug release behavior is limited. Herein, CUR-loaded platelet membrane bioinspired chitosan-modified liposome (PCLP-CUR) was constructed to improve CUR release. PCLP-CUR was shown to have long retention time, improved bioavailability, strong tumor targeting capacity and effective cellular uptake. The incorporation of chitosan enabled PCLP-CUR to release cargoes quickly under mild acidic tumor conditions, leading to more complete drug release and favoring subsequent treatment. Both in vitro and in vivo investigations showed that PCLP-CUR could significantly enhance the anticancer efficacy of CUR with minimal side effects through biomimetic membrane and chitosan modification. In summary, this developed delivery system can provide a promising strategy for tumor-targeting therapy and phytochemical delivery.

H ₂ S nanomotors show potential for the active treatment of AKI.

Acute kidney injury (AKI) is characterized by a rapid loss of renal metabolic function and a high mortality rate. Although significant progress has been made in developing targeted drugs for AKI treatment, issues such as inadequate antioxidant effects and poor renal enrichment efficiency remain. Nanomotors can enhance drug delivery efficiency in AKI treatments through self-propulsion in the microenvironment or via external stimuli. We reviewed recent progress in the targeted treatment of AKI with nanomotors, focusing on their contribution to targeted drug delivery at different stages and combined treatments. Current limitations and future development directions are also discussed.

The poly(ethylene glycol)-b-brush poly(l-lysine) polymer (PEG-b-(PELG₅₀-g-PLL₃)) was synthesized and evaluated as a nanocarrier for prolonging delivery of exenatide through the abdominal subcutaneous injection route. The isoelectric point of exenatide was 4.86, and exenatide could combine with PEG-b-(PELG₅₀-g-PLL₃) polymers via electrostatic interactions at pH 7.4. This polymer was a good candidate for achieving prolonged drug delivery for exenatide, considering its high molecular weight. Besides the physicochemical characterization of the polymer, in vitro and in vivo applications were researched as a sustained exenatide delivery system. In the in vitro release research, 20.16%–76.88% of total exenatide was released from the PEG-b-(PELG₅₀-g-PLL₃) polymer within 7 days. The synthesized block-brush polymers and exenatide–block-brush polymers were analyzed by nuclear magnetic resonance spectroscopy, gel permeation chromatography, transmission electron microscopy, nanoparticle size instrument, and scanning electron microscopy. The best formulation was selected for in vivo experimentation to achieve blood glucose control in diabetic rat models using free exenatide as the control. The hypoglycemic action of the formulation following subcutaneous injection in diabetic rats lasted 7 days, and the results indicated that exenatide–block-brush polymers demonstrate enhanced long-acting hypoglycemic action. Besides the hypoglycemic action, exenatide–block-brush polymers significantly alleviated diabetic nephropathy via improving renal function, decreasing oxidative stress injury, decreasing urinary albumin excretion rate, mitigating albumin/creatinine ratio, reducing blood lipids, abating kidney index, weakening apoptosis, and downregulating expression of connective tissue growth factor. All of the results suggested that PEG-b-(PELG₅₀-g-PLL₃) polymers could be used as potential exenatide nanocarriers, with efficient encapsulation and sustained release.

Background: The objective of this study was to survey the therapeutic function of curcumin-encapsulated poly(gamma-benzyl l-glutamate)-poly(ethylene glycol)-poly(gammabenzyl l-glutamate) (PBLG-PEG-PBLG) (P) on diabetic cardiomyopathy (DCM) via cross regulation effect of calcium-sensing receptor (CaSR) and endogenous cystathionine-γ-lyase (CSE)/hydrogen sulfide (H₂S). Methods: Diabetic rats were preconditioned with 20 mg/kg curcumin or curcumin/P complex continuously for 8 weeks. The blood and myocardiums were collected, the level of serum H₂S was observed, and the [Ca²⁺]_i content was measured in myocardial cells, and hematoxylin-eosin, CaSR, CSE, and calmodulin (CaM) expression were detected. Results: Both curcumin and curcumin/P pretreatment alleviated pathological morphological damage of myocardium, increased H₂S and [Ca²⁺]_i levels, and upregulated the expression of CaSR, CSE, and CaM as compared to DCM group, while curcumin/P remarkably augmented this effect. Conclusion: PBLG-PEG-PBLG could improve water-solubility and bioactivity of curcumin and curcumin/PBLG-PEG-PBLG significantly alleviated diabetic cardiomyopathy.