Ionizable Cholesterol Analogs as the Fifth Component of Lipid Nanoparticles for Selective Targeting Delivery of mRNA.

Lipid nanoparticles (LNP) have shown great promise in clinical applications for delivering mRNA. Targeted delivery of mRNA to particular tissues or organs is essential for precise therapeutic outcomes and minimized side effects in various disease models. However, achieving targeted delivery beyond the liver is a challenge based on current LNP formulations.

A single dose of VEGF-A circular RNA sustains in situ long-term expression of protein to accelerate diabetic wound healing.

Diabetic foot ulcer (DFU), which is characterised by damage to minute blood vessels or capillaries around wounds, is one of the most serious and dreaded complications of diabetes. It is challenging to repair chronic non-healing DFU wounds. Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis and promotes wound healing in DFU.

Tumor-activated IL-2 mRNA delivered by lipid nanoparticles for cancer immunotherapy.

Interleukin-2 (IL-2) exhibits the unique capacity to modulate immune functions, potentially exerting antitumor effects by stimulating immune responses, making it highly promising for immunotherapy. However, the clinical use of recombinant IL-2 protein faces significant limitations due to its short half-life and systemic toxicity. To overcome these challenges and fully exploit IL-2's potential in tumor immunotherapy, this study reports the development of a tumor-activated IL-2 mRNA, delivered via lipid nanoparticles (LNPs).

Paclitaxel prodrug-encapsulated polypeptide micelles with redox/pH dual responsiveness for cancer chemotherapy.

Polypeptides are a highly promising carrier for delivering hydrophobic drugs, due to their excellent biocompatibility, non-toxicity, and non-immunogenicity. Herein, a redox and pH dual-responsive poly(ethylene glycol)-SS-b-polypeptide micelles encapsulated with disulfide bridged paclitaxel-pentadecanoic acid prodrug was developed for cancer chemotherapy. First of all, disulfide bridged paclitaxel-pentadecanoic acid prodrug (PTX-SS-COOH) and poly(ethylene glycol)-SS-b-polylysine-b-polyphenylalanine (mPEG-SS-b-PLys-b-PPhe, ESLP) were synthesized and confirmed via NMR, MS, FT-IR or GPC.

Enhancing Bone Grafting Outcomes: A Comprehensive Review of Antibacterial Artificial Composite Bone Scaffolds.

Bone defects and dysfunctions are prevalent among patients, resulting from various causes such as trauma, tumors, congenital malformations, inflammation, and infection. The demand for bone defect repair materials is second only to blood transfusions. Artificial bone composites offer numerous advantages for bone damage repair, including their availability, absence of rejection or immune reactions, high malleability, exceptional mechanical strength, and outstanding biocompatibility.

Bivalent mRNA vaccines against three SARS-CoV-2 variants mediated by new ionizable lipid nanoparticles.

Lipid nanoparticles (LNPs)-based mRNA vaccines have shown great potential in the fight against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. However, it remains still a challenge to improve the delivery efficiency of LNPs and the long-term stability of their mediated mRNA vaccines. Herein, a novel ionizable lipid 2-hexyldecyl 6-(ethyl(3-((2-hexyldecyl)oxy)-2-hydroxypropyl)amino)hexanoate (HEAH) derived LNPs were developed for delivering the receptor binding domain (RBD) mRNAs.

Reduction-Responsive Docetaxel Prodrug Encapsulated within Human Serum Albumin Nanoparticles for Cancer Therapy.

Docetaxel (DTX), a semisynthetic analogue of paclitaxel, is often used to treat cancers. Owing to its poor aqueous solubility, the current formulation of DTX for clinical applications involves using high surfactant and ethanol concentrations, causing hypersensitivity reactions. To overcome this issue, we developed a reduction-responsive DTX prodrug encapsulated within human serum albumin (HSA) nanoparticles (DTX-SS-COOH/HSA NPs).

Local delivery of artesunate dimer liposomes incorporated injectable hydrogel for HO and pH-independent chemodynamic therapy.

Chemodynamic therapy (CDT) has emerged as a powerful tumor treatment option by inducing the imbalance of redox homeostasis in cancer cells. Nevertheless, the therapeutic outcomes were greatly limited because of insufficient endogenous HO and upregulated cellular antioxidant defense in the tumor microenvironment (TME). Herein, a liposome-incorporated in-situ alginate hydrogel locoregional treatment strategy was developed, which involves using hemin-loaded artesunate dimer liposomes (HAD-LP) as redox-triggered self-amplified C-center free radical nanogenerator to enhance CDT.

Novel disulfide bond bridged 7-ethyl-10-hydroxyl camptothecin-undecanoic acid conjugate/human serum albumin nanoparticles for breast cancer therapy.

7-Ethyl-10-hydroxyl camptothecin (SN38), a semisynthetic derivative of camptothecin, exhibited extreme pharmacological activities in treating a range of cancers. However, its poor aqueous solubility and low stability hinder its clinical applications. Hence, a redox-responsive SN38 prodrug encapsulated human serum albumin (HSA) nanoparticle is developed to realize its potential in the clinic.

Redox-responsive paclitaxel-pentadecanoic acid conjugate encapsulated human serum albumin nanoparticles for cancer therapy.

Human serum albumin (HSA) is an important nanocarrier of hydrophobic drugs due to its biocompatibility, bioresorbability, non-immunogenicity and intrinsic targetability. However, HSA/drug nanocomplexes have to experience complicated manufacturing process including multiple high-pressure homogenization and removing organic solvent under reduced pressure condition. Besides, the clinical application of these HSA/drug nanocomplexes is often limited because of their unsatisfactory stability and restricted dose.

Efficient delivery of VEGF-A mRNA for promoting diabetic wound healing via ionizable lipid nanoparticles.

Diabetes is often accompanied by chronic non-healing wounds, and vascularendothelial growth factor A (VEGF-A) is crucial in the treatment of chronic diabetic wounds. However, the application of VEGF-A protein in clinic is limited due to poor absorption and short half-life of protein macromolecule. Herein, we employed an emerging protein replacement therapy by delivering VEGF-A mRNA into the body to express the desired protein to accelerate diabetic wound healing.

Efficient delivery of VEGFA mRNA for promoting wound healing via ionizable lipid nanoparticles.

Vascular endothelial growth factor A (VEGFA) plays an important role in the healing of skin wound. However, the application of VEGFA protein in clinic is limited because of its high cost manufacturing, complicated purification and poor pharmacokinetic profile. Herein, we developed nucleoside-modified mRNA encoding VEGFA encapsulated ionizable lipid nanoparticles (LNP) to improve angiogenesis and increase wound healing rate.

In Situ-Activated Phospholipid-Mimic Artemisinin Prodrug via Injectable Hydrogel Nano/Microsphere for Rheumatoid Arthritis Therapy.

In situ-activated therapy is a decent option for localized diseases with improved efficacies and reduced side effects, which is heavily dependent on the local conversion or activation of bioinert components. In this work, we applied a phospholipid-mimic artemisinin prodrug (ARP) for preparing an injectable nano/microsphere to first realize an in situ-activated therapy of the typical systemically administrated artemisinin-based medicines for a localized rheumatoid arthritis (RA) lesion. ARP is simultaneously an alternative of phospholipids and an enzyme-independent activable prodrug, which can formulate "drug-in-drug" co-delivery liposomes with cargo of partner drugs (e.

Assessment of New Strategies to Improve the Performance of Antimicrobial Peptides.

In this research, we constructed a novel engineered tripeptide modified with lipoic acid (LA-RWR), followed by crosslinking of lipoic acid to form nanoparticles (c-LA-RWR). LA-RWR was also modified with phenethylamine (PEA) on the C-terminus to achieve better antibacterial activities. The as-prepared c-LA-RWR and LA-RWR-PEA were effective against , , , and methicillin-resistant , with minimum inhibitory concentration values ranging from 2 to 16 µg/mL, which greatly improved the performance of LA-RWR.

Efficient delivery of PKN3 shRNA for the treatment of breast cancer via lipid nanoparticles.

Protein kinase N3 (PKN3), an AGC-family member, is often overexpressed in breast tumor cells. RNAi therapy is a promising approach to inhibit tumor growth by reducing the expression of PKN3. In this report, lipid nanoparticles encapsulated with new shRNA PKN3 (SS-LNP/shPKN3) with redox-responsiveness were developed in order to specifically down-regulate the expression of PKN3 for breast cancer treatment.

Multifunctional Lipid Nanoparticles for Protein Kinase N3 shRNA Delivery and Prostate Cancer Therapy.

Protein kinase N3 (PKN3), by virtue of its abnormal expression in prostate cells, has been widely used as a target of RNAi (shRNA, siRNA, miRNA) therapy. The major challenges of PKN3 RNAi therapy lie in how to design effective interference sequences and delivery systems. Herein, new PKN3 shRNA sequences (shPKN3-2459 and shPKN3-3357) were designed, and bioreducible, biodegradable, ionizable lipid-based nanoparticles were developed for shPKN3 delivery.

A reduction-responsive drug delivery with improved stability: disulfide crosslinked micelles of small amiphiphilic molecules.

Micelles self-assembled from small amphiphilic molecules are unstable in biological fluids, and thus are poor drug carriers. In contrast, amphiphilic polymer micelles can encapsulate hydrophobic drugs in their core to greatly enhance their aqueous solubility and extend their retention time in blood circulation owing to their hydrophilic shell. However, the major disadvantages of conventional polymer micelles are the heterogeneity of the amphiphilic polymer structure and premature drug leakage.

Dimeric Artesunate Glycerophosphocholine Conjugate Nano-Assemblies as Slow-Release Antimalarials to Overcome Kelch 13 Mutant Artemisinin Resistance.

Current best practice for the treatment of malaria relies on short half-life artemisinins that are failing against emerging Kelch 13 mutant parasite strains. Here, we introduce a liposome-like self-assembly of a dimeric artesunate glycerophosphocholine conjugate (dAPC-S) as an amphiphilic prodrug for the short-lived antimalarial drug, dihydroartemisinin (DHA), with enhanced killing of Kelch 13 mutant artemisinin-resistant parasites. Cryo-electron microscopy (cryoEM) images and the dynamic light scattering (DLS) technique show that dAPC-S typically exhibits a multilamellar liposomal structure with a size distribution similar to that of the liposomes generated using thin-film dispersion (dAPC-L).

A modified thin film method for large scale production of dimeric artesunate phospholipid liposomes and comparison with conventional approaches.

Dimeric artesunate phospholipid (ART-GPC), an amphiphilic derivative of artemisinin dimer reported in our previous work, can be applied to treat malaria effectively. The objective of this study is to develop a facile method for the industrial production of ART-GPC liposomes. Conventional methods including thin film hydration (TFH), ethanol injection (EI), and freeze drying (FD) were used to prepare ART-GPC liposomes, and the resultants presented poor physicochemical properties.

Dimeric artesunate-choline conjugate micelles coated with hyaluronic acid as a stable, safe and potent alternative anti-malarial injection of artesunate.

Artesunate (ARS) is the only artemisinin-based intravenous drug approved for treatment of malaria in the clinic. ARS is rapidly metabolized in vivo to short lived (∼30-45 min) but fast acting, dihydroartemisinin (DHA). The short half-life of DHA necessitates multiple dose administration to circumvent the risk of recrudescence and development of artemisinin resistance.

Dimeric Artesunate-Phosphatidylcholine-Based Liposomes for Irinotecan Delivery as a Combination Therapy Approach.

In this work, dimeric artesunate-phosphatidylcholine conjugate (dARTPC)-based liposomes encapsulated with irinotecan (Ir) were developed for anticancer combination therapy. First, dARTPC featured with unique amphipathic properties formed liposomes by classical thin-film methods. After that, Ir was encapsulated into dARTPC-based liposomes (Ir/dARTPC-LP) by the triethylammonium sucrose octasulfate gradient method.

Redox-sensitive irinotecan liposomes with active ultra-high loading and enhanced intracellular drug release.

In this report, a novel irinotecan (IR) encapsulated redox-responsive liposome was developed. The redox-responsive liposomes were prepared based on disulfide phosphatidylcholine (SS-PC), DSPC, DSPE-PEG2000 and cholesterol by ethanol injection method. IR was actively loaded by triethylammonium sucrose octasulfate (TEA8-SOS) gradient method to generate IR/SS-PC liposomes (IR/SS-LP).