Improved Water Solubility Research Articles

Design, synthesis and evaluation of halogenated phenazine antibacterial prodrugs targeting nitroreductase enzymes for activation.

It is of great importance to develop new strategies to combat antibiotic resistance. Our lab has discovered halogenated phenazine (HP) analogues that are highly active against multidrug-resistant bacterial pathogens. Here, we report the design, synthesis, and study of a new series of nitroarene-based HP prodrugs that leverage intracellular nitroreductase (NTR) enzymes for activation and subsequent release of active HP agents. Our goals of developing HP prodrugs are to (1) mitigate off-target metal chelation (potential toxicity), (2) possess motifs to facilitate intracellular, bacterial-specific HP release, (3) improve water solubility, and (4) prevent undesirable metabolism (e.g., glucuronidation of HP's phenol). Following the synthesis of HP-nitroarene prodrugs bearing a sulfonate ester linker, NTR-promoted release experiments demonstrated prodrug HP-1-N released 70.1% of parent HP-1 after 16 hours (with only 6.8% HP-1 release without NTR). In analogous in vitro experiments, no HP release was observed for control sulfonate ester compounds lacking the critical nitro group. When compared to parent HP compounds, nitroarene prodrugs evaluated during these studies demonstrate similar antibacterial activities in MIC and zone of inhibition assays (against lab strains and clinical isolates). In conclusion, HP-nitroarene prodrugs could provide a future avenue to develop potent agents that target antibiotic resistant bacteria.

Detection of aqueous and gaseous hydrogen sulfide with lanthanide-macrocycle binary complexes.

Two novel, discrete lanthanide-macrocycle binary complexes for the detection of hydrogen sulfide are reported. The hydrogen sulfide sensing mechanism utilises the copper sequestration at a secondary binding site, with resulting bimetallic lanthanide(III)/copper(II) complexes (Ln = Eu3+ and Tb3+) exhibiting high selectivity, good sensitivity and excellent reversibility for aqueous hydrogen sulfide. The inclusion of the DO2A macrocycle and 4-(2-pyridyl)-1,2,3-triazole dipicolinic acid ligand, results in a complex with good solubility and stability. The europium(III) complex also displayed a low limit of detection (665 ppb) with a response time of 30 seconds with gaseous hydrogen sulfide. The improved water solubility and stability over a previous complex results in these sensors having the potential for use in environmental monitoring and biological studies for various functional settings.

Fluorescent styryl pyridine-N-oxide probes for imaging lipid droplets.

Lipid droplets (LDs) have emerged as major regulators of cellular metabolism, encompassing lipid storage, membrane synthesis, viral replication, and protein degradation. Exclusive studies have suggested a direct link between LDs and cancer, as a notable abundance of LDs is found in cancerous cells. Therefore, monitoring the location, distribution, and movements of LDs is of paramount importance for understanding their involvement in biological processes. To target LDs, we designed and synthesized fluorophores with a styryl scaffold bearing electron-donating amino groups and pyridine-N-oxide, a zwitterionic acceptor moiety. We explored their photophysical properties in various solvents and conducted systematic DFT calculations on the synthesized fluorescent molecules, comparing them with neutral pyridine and cationic pyridinium styryl dyes. The results demonstrate that diphenylaminostyryl pyridine-N-oxide (TNO) shows excellent imaging of LDs, in contrast to the behavior of cationic styrylpyridinium (TNC), which primarily localizes within the mitochondria. Notably, pyridine N-oxide offers several benefits: an increased dipole moment facilitating charge separation between donors and acceptors, substantial HOMO and LUMO stabilization, improved water solubility, favorable redox properties, and bathochromic-shifted absorption/emission spectra, showing promise as a fluorescent tool for probing the cellular-biological realm.

Recent Advances in Pyridine Scaffold: Focus on Chemistry, Synthesis, and Antibacterial Activities.

Multidrug-resistant (MDR) pathogens have created a fatal problem for human health and antimicrobial treatment. Among the currently available antibiotics, many are inactive against MDR pathogens. In this context, heterocyclic compounds/drugs play a vital role. Thus, it is very much essential to explore new research to combat the issue. Of the available nitrogen-bearing heterocyclic compounds/drugs, pyridine derivatives are of special interest due to their solubility. Encouragingly, some of the newly synthesized pyridine compounds/drugs are found to inhibit multidrug-resistant S. aureus (MRSA). Pyridine scaffold bearing poor basicity generally improves water solubility in pharmaceutically potential molecules and has led to the discovery of numerous broad-spectrum therapeutic agents. Keeping these in mind, we have reviewed the chemistry, recent synthetic techniques, and bacterial preventative activity of pyridine derivatives since 2015. This will facilitate the development of pyridine-based novel antibiotic/drug design in the near future as a versatile scaffold with limited side effects for the next-generation therapeutics.

Exploring Mannosylpurines as Copper Chelators and Cholinesterase Inhibitors with Potential for Alzheimer's Disease.

Alzheimer's Disease (AD) is characterized by a progressive cholinergic neurotransmission imbalance, with a decrease of acetylcholinesterase (AChE) activity followed by a significant increase of butyrylcholinesterase (BChE) in the later AD stages. BChE activity is also crucial for the development of Aβ plaques, the main hallmarks of this pathology. Moreover, systemic copper dyshomeostasis alters neurotransmission leading to AD. In the search for structures targeting both events, a set of novel 6-benzamide purine nucleosides was synthesized, differing in glycone configuration and N7/N9 linkage to the purine. Their AChE/BChE inhibitory activity and metal ion chelating properties were evaluated. Selectivity for human BChE inhibition required N9-linked 6-deoxy-α-d-mannosylpurine structure, while all three tested β-d-derivatives appeared as non-selective inhibitors. The N9-linked l-nucleosides were cholinesterase inhibitors except the one embodying either the acetylated sugar or the N-benzyl-protected nucleobase. These findings highlight that sugar-enriched molecular entities can tune bioactivity and selectivity against cholinesterases. In addition, selective copper chelating properties over zinc, aluminum, and iron were found for the benzyl and acetyl-protected 6-deoxy-α-l-mannosyl N9-linked purine nucleosides. Computational studies highlight molecular conformations and the chelating molecular site. The first dual target compounds were disclosed with the perspective of generating drug candidates by improving water solubility.

On the formulation of disulfide herbicides based on aminophenoxazinones: polymeric nanoparticle formulation and cyclodextrin complexation to combat crop yield losses.

The resistance of weeds to herbicides is a significant issue in ensuring future food supply. Specific examples are Plantago lanceolata, Portulaca oleracea and Lolium rigidum, which mainly infect rice, wheat, barley and pastures, and cause high yield losses every year. In this regard, natural products and their mimics have provided new hope as a result of their different modes-of-action, activity at low concentrations and reduced pollution effects relative to conventional herbicides. However, the poor water solubility and physicochemical properties of these compounds limit their broad application. These problems can be addressed by formulation techniques, and encapsulation appears to be of great interest. Disulfide herbicides inspired by aminophenoxazinones have been formulated with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), γ-CD and polymeric nanoparticles (NPs). In silico studies were employed to identify which complexes would be generated and complex formation was confirmed by nuclear magnetic resonance spectroscopy. Solubility diagrams were generated to assess any improvement in water solubility, which was enhanced 2-13-fold. Scanning electron microscopy and energy-dispersive X-ray spectra confirmed the success of the formulation process for the nanoparticles. Formulated compounds were evaluated in an in vitro wheat coleoptile bioassay, with almost 100% elongation inhibition achieved using only water for the bioassay. Specific in vitro testing on weed phytotoxicity showed that the application of core/shell NPs is highly effective in the fight against P.lanceolata seed germination. The formulation of disulfide herbicides with CD complexes and NPs led to an enhancement in water solubility and bioactivity. These systems can be applied in pre-emergent mode against P.lanceolata, using only water to prepare the sample, and they showed better activity than the positive controls. © 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Identification of “dual-site”-binding diarylpyrimidines targeting both NNIBP and the NNRTI adjacent site of the HIV-1 reverse transcriptase

Here, we reported a novel series of “dual-site” binding diarylpyrimidine (DAPY) derivatives targeting both the NNRTI adjacent site and NNRTIs binding pocket (NNIBP). The anti-HIV-1 activity results demonstrated that compound 9e (EC50 = 2.04–61.1 nM) displayed robust potencies against a panel of HIV-1 NNRTIs-resistant strains, being comparable to that of etravirine (ETR). Moreover, 9e displayed much lower cytotoxicity (CC50 = 59.2 μM) and higher SI values (4605) toward wild-type HIV-1 strain. The HIV-1 RT enzyme inhibitory activity clarified the binding target of 9e was HIV-1 RT (IC50 = 0.019 μM). Furthermore, the molecular modeling study was also investigated to give a reasonable explanation of the preliminary SARs. Further test indicated that 9e possessed significantly improved water solubility under pH 7.0 and 7.4 conditions. Additionally, the in silico prediction of physicochemical properties and CYP enzymatic inhibitory ability were investigated to evaluate their drug-like features. Consequently, compound 9e showed the highest activity and low cytotoxicity, which could be used as a lead for further modification to obtain potent HIV-1 NNRTIs.

A Cleavable Self-Inclusion Conjugate with Enhanced Biocompatibility and Antitumor Bioactivity

A Cleavable Self-Inclusion Conjugate with Enhanced Biocompatibility and Antitumor Bioactivity

Binary and ternary inclusion complexation of lapatinib ditosylate with β-cyclodextrin: preparation, evaluation and in vitro anticancer activity

BackgroundLapatinib ditosylate, an efficient tyrosine kinase inhibitor for breast cancer, poses pharmacokinetic issues, hence developing its oral delivery system is troublesome. The poor aqueous solubility of this medicament is a key impediment in developing its successful formulation. So, the current study aims to improve water solubility of Lapatinib ditosylate by using complexation technique with β-cyclodextrin and a suitable ternary agent.ResultsBinary and ternary complexes of Lapatinib ditosylate were synthesized by means of kneading and lyophilization using β-cyclodextrin and PVP K30. As a ternary agent, various hydrophilic polymers, as well as organic acids, were assessed, and PVP K30 was chosen for the final formulation based on its stability constant and complexation efficiency. When compared to pure Lapatinib ditosylate, both inclusion complexes demonstrated improved solubility, and drug dissolution. Differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), Fourier transform infrared (FTIR), and scanning electron microscopic (SEM) techniques, all validated the complex formation. Docking studies picturized the geometry of Lapatinib ditosylate in β-cyclodextrin cavity. Using MCF-7 cell lines, investigation of anticancer activity of the pure drug and its synthesized complexes was carried out and the results revealed that the complexes had stronger anticancer activity than Lapatinib ditosylate alone.ConclusionsOverall, it can be concluded that Lapatinib ditosylate complexation increased its aqueous solubility, resulting in its increased dissolution and in vitro anticancer activity in a breast cancer cell line.

Thermal-assisted synthesis of ferulic acid-chitosan complex in water and its application as safe antioxidant

Safe antioxidants are highly demanded in food preservation, yet existing preparation methods of typical bio-based antioxidants all suffer from either toxic catalysts or poor water solubility of the products. Herein, a water-soluble safe antioxidant, ferulic acid-chitosan complex, was facilely prepared in water with the assistance of mild-temperature heating. The chemical structure of ferulic acid-chitosan complex was determined by spectroscopy, and its thermal stability and rheological properties were studied in detail. Different from its precursors, the ferulic acid-chitosan complex exhibits much improved water solubility, thanks to its ionic structure. The as-prepared chitosan-ferulic acid complex displays higher antioxidative property than free ferulic acid, which was illustrated by the good preservation of freshly prepared apple juice. Such thermal-assisted synthesis strategy is demonstrated as an effective approach to prepare hydrophilic chitosan complex bearing hydrophobic organic acid, which enables great feasibility to the development of chitosan-based functional biomaterials.

Synthesis and characterization of thiazolium chitosan derivative with enhanced antimicrobial properties and its use as component of chitosan based films

In this work, chemical modification of chitosan using cationic thiazolium groups was investigated with the aim to improve water solubility and antimicrobial properties of chitosan. Enzymatic synthesis and ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS) chemistry were employed to synthesize and attach to chitosan through the amine groups the molecule bearing thiazolium moieties, quaternized 4-(2-(4-methylthiazol-5-yl) ethoxy)-4-oxobutanoic acid (MTBAQ). On the basis of Fourier transform infrared spectroscopy (FTIR), elemental analysis and solid state nuclear magnetic resonance (ssNMR), around 95 % of the available amine groups of chitosan (of 25 % degree of acetylation) reacted. The resulting derivative was water soluble at physiological pH and exhibit excellent antimicrobial activity against Listeria innocua, Staphylococcus epidermidis, Staphylococcus aureus and Methicillin Resistant S. aureus Gram-positive bacteria (MIC = 8–32 μg/ mL), whereas its efficiency decreases against fungi Candida albicans and Eschericia coli Gram-negative bacterium. Subsequently, the thiazolium chitosan derivative was employed as antimicrobial component (up to 7 wt%) of chitosan/glycerol based films. The incorporation of the chitosan derivative does not modify significantly the characteristics of the film in terms of thermal and mechanical properties, while enhances considerably the antimicrobial activity.

High-Contrast Luminescent Immunohistochemistry Using PEGylated Lanthanide Complexes.

Immunohistochemistry (IHC) using fluorescent probes provides high resolution with multiplexing capability, but the imaging contrast is limited by the brightness of the fluorescent probe and the intrinsic autofluorescence background from tissues. Herein, we improved the contrast by high-density labeling of long-lifetime lanthanide complexes and time-gated imaging. As the large (∼280 nm) Stokes shift of lanthanide complexes effectively prevents the issue of concentration quenching, we succeeded in conjugating seven europium complexes to an eight-arm hydrophilic poly(ethylene glycol) (PEG) linker for signal amplification with improved water solubility to the level of up to 10 mg/mL. Moreover, we demonstrated that both human epidermal growth factor receptor 2 (HER2) in a formalin-fixed paraffin-embedded (FFPE) tissue section and cytokeratin 18 (CK18) in a frozen section can be resolved with the enhanced contrast by 2-fold and 3-fold, respectively. Furthermore, we show that the PEGylation of multiple lanthanide complexes is compatible with tyramide signal amplification (TSA). This work suggests new opportunities for sensitive imaging of low-abundance biomarkers in a tissue matrix.

Mitochondria-targeted pentacyclic triterpenoid carbon dots for selective cancer cell destruction via inducing autophagy, apoptosis, as well as ferroptosis

Natural products have been an important database for anti-cancer drug development. However, low water solubility and poor biocompatibility limit the efficacy of natural products. Carbon dots (CDs), as an emerging 0D material, have unique properties in bioimaging, water solubility and biocompatibility. Here, we prepared three pentacyclic triterpenoids (PTs) included glycyrrhetinic acid (GA), ursolic acid (UA) and oleanolic acid (OA), which have anticancer activity but poor water solubility, as raw materials into CDs to improve disadvantages. Our data indicated that the active surface groups of all three CDs were largely preserved and were able to excite green fluorescence. Their carboxyl edges not only exhibited excellent water solubility, but also specifically targeted tumor cell mitochondria due to high sensitivity to ROS-induced damage and high internal oxidative stress. In cancer cells, the PT-CDs induced cell death through three pathways (apoptosis, ferroptosis, and autophagy), which is essentially the same way their raw materials induce death, but the effect was much stronger than raw materials. Notably, functionalized PT-CDs also exhibited extremely low toxicity. In summary, PT-CDs not only have improved water solubility and biocompatibility, but also retain the structure of their raw materials well and exert better efficacy, which provides new ideas for the development of anti-cancer natural product drugs.

A water-soluble two-photon fluorescent probe for rapid and reversible monitoring of redox state

Redox homeostasis is the guarantee for the normal operation of living organisms. Given its importance, monitoring dynamic changes of redox state will facilitate the study of relevant physiological and pathological processes. Herein, a two-photon fluorescent probe NA-Se with selenomorpholine as the response site has been developed for reversible detection of redox state. NA-Se exhibits outstanding analytical performance, including a rapid response to ClO− within 8 s, a detection limit as low as 13.3 nM, and at least 10 redox reversible cycles. Furthermore, NA-Se has improved water solubility and extremely low cytotoxicity, making it ideal for bioimaging. Finally, NA-Se has been successfully applied to monitor the ClO−/GSH redox cycle in living cells and zebrafish. This work may provide an effective tool for studying redox state and related diseases in vivo.

Preparation, in vitro and in vivo evaluation of pinocembrin-loaded TPGS modified liposomes with enhanced bioavailability and antihyperglycemic activity

Purpose To prepare polyethylene glycol succinate-vitamin E modified pinocembrin (PCB)-loaded liposomes (PCBT-liposomes) and evaluate PCBT-liposomal pharmacokinetics and antihyperglycemic activity. Significance The novel PCBT-liposomes demonstrated a promising application prospect as a nano drug carrier for future research. Methods Thin film dispersion was used to prepare PCBT-liposomes. We measured a series of characterization, followed by in vitro cumulative release, in vivo pharmacokinetic study, and antihyperglycemic activity evaluation. Results PCBT-liposomes displayed spherical and bilayered nanoparticles with mean particle size (roughly 92 nm), negative zeta potential (about −26.650 mV), high drug encapsulation efficiency (87.32 ± 1.34%) and good storage (at 4 or 25 °C) stability during 48 h after hydration. The cumulative release rate of PCBT-liposomes was markedly higher than free PCB in four different pH media. In vivo investigation showed that PCBT-liposomes could obviously improve oral bioavailability of PCB by 1.96 times, whereas the C max, MRT0– t , and T 1/2 of PCBT-liposomes were roughly 1.700 ± 0.139 µg·mL−1, 12.695 ± 1.647 h, and 14.244 h, respectively. In terms of biochemical analysis, aspartate amino-transferase (AST), alanine amino-transferase (ALT), interleukin-1 (IL-1), and tumor necrosis factor-α (TNF-α) concentrations in serum of diabetic mice were respectively decreased 28.28%, 17.23%, 17.77%, and 8.08% after PCBT-liposomal treatment. Conclusion These results show PCBT-liposomal preparation as an excellent nano-carrier which has the potential to improve water solubility, bioavailability, and antihyperglycemic activity of PCB, amid broadening the application of PCB in the clinical settings.

Facile approach for surfactant-free synthesis of Au@ginsenoside Rh2 nanoparticles and researches on anticancer activity

BackgroundInorganic nanocomposites especially Au nanostructures have exhibited outstanding physicochemical properties in biomedical fields. For further clinical applications on theranostics, especially drug delivery, numerous explorations of green and facile synthesis methods combining with pharmacoactive natural components have been investigated to construct safe and multifunctional bioactive Au nanoparticles (NPs). Ginsenoside Rh2 is protopanaxadiol type compound isolated from plants of genus Panax, with excellent anticancer effect and antioxidant activity. In this research, we prepared the novel Au nanoparticles using ginsenoside Rh2 as both reducing and stabilizing agents.ResultsThe synthesized Au@ginsenoside Rh2 NPs were proved to exhibit desirable inhibitory effect on different cancer cell lines, which benefited from the inherent anticancer effect of the ginsenoside Rh2. Investigations in vitro indicated that Au@ginsenoside Rh2 NPs inhibited cell proliferation, cell migration and invasion, induced cell cycle arrest, enhanced the reactive oxygen species (ROS) generation, and regulated the protein expressions of caspase-3, 8, 9 to trigger cell apoptosis as well.ConclusionsBecause of the absence of toxic chemical surfactants, the eco-friendly synthesis method of Au NPs modified by natural phytochemicals avoided tedious separation and modification processes. On the other hand, Au@ginsenoside Rh2 NPs also improved water solubility and bioavailability of the hydrophobic drug ginsenoside Rh2. It broadened minds for preparation and application of traditional Chinese medicines (TCMs) modified metal nanoparticles and deserved further study.

Design, synthesis, and biological evaluation of novel sulfamoylbenzamide derivatives as HBV capsid assembly modulators

Capsid assembly modulators (CAMs) represent a novel class of antiviral agents targeting hepatitis B virus (HBV) capsid to disrupt the assembly process. NVR 3-778 is the first CAM to demonstrate antiviral activity in patients infected with HBV. However, the relatively low aqueous solubility and moderate activity in the human body halted further development of NVR 3-778. To improve the anti-HBV activity and the drug-like properties of NVR 3-778, we designed and synthesized a series of NVR 3-778 derivatives. Notably, phenylboronic acid-bearing compound 7b (EC50 = 0.83 ± 0.33 µM, CC50 = 19.4 ± 5.0 µM) displayed comparable anti-HBV activity to NVR 3-778 (EC50 = 0.73 ± 0.20 µM, CC50 = 23.4 ± 7.0 µM). Besides, 7b showed improved water solubility (328.8 µg/mL, pH 7) compared to NVR 3-778 (35.8 µg/mL, pH 7). Size exclusion chromatography (SEC) and quantification of encapsidated viral RNA were used to demonstrate that 7b behaves as a class II CAM similar to NVR 3-778. Moreover, molecular dynamics (MD) simulations were conducted to rationalize the structure–activity relationships (SARs) of these novel derivatives and to understand their key interactions with the binding pocket, which provide useful indications for guiding the further rational design of more effective anti-HBV drugs.

Production of Thermoplastic Starch-Aloe vera Gel Film with High Tensile Strength and Improved Water Solubility.

Biodegradable film packaging made from thermoplastic starch (TPS) has low mechanical performance and high water solubility, which is incomparable with synthetic films. In this work, Aloe vera (AV) gel and plasticized soluble potato starch were utilised to improve the mechanical stability and water solubility of TPS. Dried starch was mixed with glycerol and different AV gel concentrations (0% to 50%). The TPS + 50% AV gel (30 g TPS + 15 g AV gel) showed the best improvement compared to TPS alone. When compared to similar TPS films with AV gel added, this film is stronger and dissolves better in water. Mechanical qualities improved the tensile strength and Young’s modulus of the TPS film, with 1.03 MPa to 9.14 MPa and 51.92 MPa to 769.00 MPa, respectively. This was supported by the improvement of TPS water solubility from 57.44% to 46.6% and also by the increase in decomposition temperature of the TPS. This promises better heat resistance. The crystallinity percentage increase to 24.26% suggested that the formation of hydrogen bonding between TPS and AV gel enhanced crosslinking in the polymeric structure. By adding AV gel, the TPS polymeric structure is improved and can be used as a biodegradable food-packaging film.

Co-assembling nanoparticles of Asiatic acid and Caffeic acid phenethyl ester: Characterization, stability and bioactivity in vitro

Caffeic acid phenethyl ester (CAPE) is an efficient bioactive polyphenol ester derived from propolis. However, its poor water solubility, bioavailability, and stability significantly limit its application. Based on the assembly properties of some natural small molecules (NSMs), asiatic acid-caffeic acid phenethyl ester nanoparticles (ASA-CAPE NPs) were prepared to overcome the above defects. After proportion optimization, the encapsulation and loading efficiencies of ASA-CAPE NPs reached 47.72 ± 0.17 % and 11.62 ± 0.42 %, respectively. Characterization results showed that ASA-CAPE NPs, mainly assembled by hydrogen bonds and hydrophobic forces, possessed regular spherical morphology with a diameter size of less than 300 nm. Additionally, ASA-CAPE NPs presented improved water solubility, stability, and bioactivities than free CAPE. Besides, ASA-CAPE NPs also exhibited good sustained release of CAPE during the gastrointestinal digestion in vitro. Above all, ASA-CAPE NPs provide a new idea for efficiently utilizing hydrophobic active compounds in the functional food field.

Biomimetic Red Blood Cell Membrane-Mediated Nanodrugs Loading Ursolic Acid for Targeting NSCLC Therapy.

Simple SummaryLung cancer is the second most common cancer after breast cancer. Non-small-cell lung cancer, which represents more than 85% of all lung cancer subtypes, is known for its tumor progression and metastasis, resulting in poor clinical outcomes. Conventional therapies for NSCLC, such as surgery, chemotherapy, and radiotherapy, always fail due to therapeutic resistance. In recent years, ursolic acid (UA), a natural pentacyclic triterpenoid compound, has been shown to be a promising antitumor drug by regulating multiple signaling pathways in cancers. Unfortunately, the poor water solubility, low bioavailability, and systemic toxicity of UA limit its clinical application. In this study, a biomimetic red blood cell membrane nanocarrier was developed to deliver UA to targeted tumor sites efficiently, and it inhibited tumor growth by inducing the apoptosis and autophagy of cancer cells both in vitro and in vivo.As one of the most common cancers worldwide, non-small-cell lung cancer (NSCLC) treatment always fails owing to the tumor microenvironment and resistance. UA, a traditional Chinese medicine, was reported to have antitumor potential in tumor models in vitro and in vivo, but showed impressive results in its potential application for poor water solubility. In this study, a novel biomimetic drug-delivery system based on UA-loaded nanoparticles (UaNPs) with a red blood cell membrane (RBCM) coating was developed. The RBCM-coated UANPs (UMNPs) exhibited improved water solubility, high stability, good biosafety, and efficient tumor accumulation. Importantly, the excellent antitumor efficiency of the UMNPs was confirmed both in vitro and in vivo in cancer models. In addition, we further investigated the antitumor mechanism of UMNPs. The results of Western blotting showed that UMNPs exerted an anticancer effect by inducing the apoptosis and autophagy of NSCLC cells, which makes it superior to free UA. In addition, body weight monitoring, hematoxylin and eosin (HE) analysis, and immunohistochemical (IHC) analysis showed no significant difference between UMNPs and the control group, indicating the safety of UMNPs. Altogether, the preparation of biomimetic UMNPs provides a promising strategy to improve outcomes in NSCLC.