Exemplifying interspecies variation of liposome fate by the effects of anti-PEG antibodies.

The different fate of liposomes among species has been discovered and mentioned in many studies, but the underlying mechanisms have not been explored. In the present work, we concentrated on the fate of PEGylated liposomes (sLip) in three commonly used species (mice, rats, and dogs). It was exhibited that the accelerated blood clearance (ABC) phenomenon and hypersensitivity in large animals (beagle dogs) were much more significant than that in rodents.

Fully human single-domain antibody targeting a highly conserved cryptic epitope on the Nipah virus G protein.

Nipah virus infection, one of the top priority diseases recognized by the World Health Organization, underscores the urgent need to develop effective countermeasures against potential epidemics and pandemics. Here, we identify a fully human single-domain antibody that targets a highly conserved cryptic epitope situated at the dimeric interface of the Nipah virus G protein (receptor binding protein, RBP), as elucidated through structures by high-resolution cryo-electron microscopy (cryo-EM). This unique binding mode disrupts the tetramerization of the G protein, consequently obstructing the activation of the F protein and inhibiting viral membrane fusion.

Brain-targeted drug delivery by in vivo functionalized liposome with stable D-peptide ligand.

Brain-targeted drug delivery poses a great challenge due to the blood-brain barrier (BBB). In a previous study, we have developed a peptide-modified stealth liposome (SP-sLip) to enhance BBB penetration via the adsorption of apolipoproteins in plasma. SP is an 11-amino acid peptide derived from 25 to 35 of the Amyloid β peptide (Aβ), which is a nature ligand of apolipoproteins.

Enhancing the Antitumor Efficacy of Oncolytic Adenovirus Through Sonodynamic Therapy-Augmented Virus Replication.

The therapeutic efficacy of oncolytic adenoviruses (OAs) relies on efficient viral transduction and replication. However, the limited expression of coxsackie-adenovirus receptors in many tumors, along with the intracellular antiviral signaling, poses significant obstacles to OA infection and oncolysis. Here, we present sonosensitizer-armed OAs (saOAs) that potentiate the antitumor efficacy of oncolytic virotherapy through sonodynamic therapy-augmented virus replication.

Effects of Surface IR783 Density on the In Vivo Behavior and Imaging Performance of Liposomes.

Nanoparticles conjugated with fluorescent probes have versatile applications, serving not only for targeted fluorescent imaging but also for evaluating the in vivo profiles of designed nanoparticles. However, the relationship between fluorophore density and nanoparticle behavior remains unexplored. The IR783-modified liposomes (IR783-sLip) were prepared through a modified ethanol injection and extrusion method.

Optimized RNA interference therapeutics combined with interleukin-2 mRNA for treating hepatitis B virus infection.

This study aimed to develop a pan-genotypic and multifunctional small interfering RNA (siRNA) against hepatitis B virus (HBV) with an efficient delivery system for treating chronic hepatitis B (CHB), and explore combined RNA interference (RNAi) and immune modulatory modalities for better viral control. Twenty synthetic siRNAs targeting consensus motifs distributed across the whole HBV genome were designed and evaluated. The lipid nanoparticle (LNP) formulation was optimized by adopting HO-PEG-DMG lipid and modifying the molar ratio of traditional polyethylene glycol (PEG) lipid in LNP prescriptions.

Design, Synthesis, Formulation, and Bioevaluation of Trisubstituted Triazines as Highly Selective mTOR Inhibitors for the Treatment of Human Breast Cancer.

The aberrant activation of the PI3K/mTOR signaling pathway is implicated in various human cancers. Thus, the development of inhibitors targeting mTOR has attracted considerable attention. In this study, we used a structure-based drug design strategy to discover a highly potent and kinase-selective mTOR inhibitor (), which demonstrated an mTOR inhibitory IC value of 1.

A natural IgM hitchhiking strategy for delivery of cancer nanovaccines to splenic marginal zone B cells.

B cell-targeted cancer vaccines are receiving increasing attention in immunotherapy due to the combined antibody-secreting and antigen-presenting functions. In this study, we propose a natural IgM-hitchhiking delivery strategy to co-deliver tumor antigens and adjuvants to splenic marginal zone B (MZB) cells. We constructed nanovaccines (FA-sLip/OVA/MPLA) consisting of classical folic acid (FA)-conjugated liposomes co-loaded with ovalbumin (OVA) and toll-like receptor 4 agonists, MPLA.

mIgM-mediated splenic marginal zone B cells targeting of folic acid for immunological evasion.

Folic acid is a fully oxidized synthetic folate with high bioavailability and stability which has been extensively prescribed to prevent congenital disabilities. Here we revealed the immunosuppressive effect of folic acid by targeting splenic marginal zone B (MZB) cells. Folic acid demonstrates avid binding with the Fc domain of immunoglobulin M (IgM), targeting IgM positive MZB cells to destabilize IgM-B cell receptor (BCR) complex and block immune responses.

Effects of PEG antibodies on in vivo performance of LNP-mRNA vaccines.

Polyethylene glycol (PEG) plays important roles in stabilizing and lengthening circulation time of lipid nanoparticle (LNP) vaccines. Nowadays various levels of PEG antibodies have been detected in human blood, but the impact and mechanism of PEG antibodies on the in vivo performance of LNP vaccines has not been clarified thoroughly. By illustrating the distribution characteristics of PEG antibodies in human, the present study focused on the influence of PEG antibodies on the safety and efficacy of LNP-mRNA vaccine against COVID-19 in animal models.

Protein corona on brain targeted nanocarriers: Challenges and prospects.

Safe and efficient medical therapy for brain diseases is still an unmet clinical need due to various barriers represented by the blood-brain barrier. Well-designed brain targeted nanocarriers are potential solutions for enhanced brain drug delivery; however, the complicated in vivo process attenuates performance of nanocarriers, which severely hampers clinical translation. The formation of protein corona (PC) is inevitable for nanocarriers circulation and transport in biofluids, acting as an important factor to regulate in vivo performance of nanocarriers.

Interplay between Liposomes and IgM: Principles, Challenges, and Opportunities.

Liposomes have received tremendous attention as a class of versatile pharmaceutical vehicles of great potential over the past several decades. However, the application of liposomes encounters major challenges due to the knowledge gaps in their in vivo delivery process. Immunoglobulin M (IgM) displays both pervasiveness and complexity in regulating the biological functions as well as eliciting adverse effects of liposomes.

Albumin-Hitchhiking Drug Delivery to Tumor-Draining Lymph Nodes Precisely Boosts Tumor-Specific Immunity through Autophagy Modulation of Immune Cells.

Tumor-draining lymph nodes (TDLNs) are the first sites where tumor components reach and dendritic cells (DCs) present tumor-associated antigens to T cells. DCs rely on autophagy to process tumor antigens into epitope peptides to form epitope-MHC complexes. Selective delivery of autophagy-stimulating drugs to TDLNs may be a precise strategy to boost chemotherapy-induced antitumor immunity.

Lipid-Based Nanocarriers Enabled Oral Delivery of Oleanolic Acid Derivative DKS26 for Diabetes Management.

Oleanolic acid derivative DKS26 has hypolipidemic, islet, and hepatoprotective effects. However, high lipophilicity and low water solubility led to DKS26 extremely low oral bioavailability. Herein, lipid-based nanocarriers, including lipid nanodiscs (sND/DKS26) and liposomes (sLip/DKS26), are prepared to improve DKS26 oral absorption.

Protein corona mediated liposomal drug delivery for bacterial infection management.

Liposomes have been widely investigated as a class of promising antibiotic delivery systems for the treatment of life-threatening bacterial infections. However, the inevitable formation of protein corona on the liposomal surface can heavily impact performance. A better understanding of the effects of protein corona on liposomal behavior can significantly improve antibacterial liposomal drug development.

Photoresponsive prodrug-dye nanoassembly for in-situ monitorable cancer therapy.

Photocleavable prodrugs enable controllable drug delivery to target sites modulated by light irradiation. However, the in vivo utility is usually hindered by their insolubility and inefficient delivery. In this study, we report a simple strategy of co-assembling boron-dipyrromethene-chlorambucil prodrug and near-infrared dye IR783 to fabricate photoresponsive nanoassemblies, which achieved both high prodrug loading capacity (~99%) and efficient light-triggered prodrug activation.

Folic Acid Enables Targeting Delivery of Lipodiscs by Circumventing IgM-Mediated Opsonization.

Folic acid (FA) is one of the most widely utilized small-molecule ligands for cancer targeted drug delivery. Natural IgM was recently found to avidly absorb on the surface of FA-functionalized liposomes (FA-sLip), negatively regulating the performance by efficiently activating complement. Herein, FA-functionalized lipodiscs (FA-Disc) were constructed to successfully circumvent IgM-mediated opsonization and retained binding activity with folate receptors .

Engineered platelets-based drug delivery platform for targeted thrombolysis.

Thrombolytic agents have thus far yielded limited therapeutic benefits in the treatment of thrombotic disease due to their short half-life, low targeting ability, and association with serious adverse reactions, such as bleeding complications. Inspired by the natural roles of platelets during thrombus formation, we fabricated a platelet-based delivery system (NO@uPA/PLTs) comprising urokinase (uPA) and arginine (Arg) for targeted thrombolysis and inhibition of re-embolism. The anchoring of uPA to the platelet surface by lipid insertion increased the thrombotic targeting and circulation duration of uPA without disturbing platelet functions.

Protein corona: challenges and opportunities for targeted delivery of nanomedicines.

Introduction: Targeted drug delivery has been widely explored as a promising way to improve the performance of nanomedicines. However, protein corona formed on the nano-surface represents a major issue that has great impacts on the fate of targeting nanomedicines, which has been overlooked in the past. With the increasing understanding of protein corona in the recent decade, many efforts have been made to improve targeting efficacy.

Peptide-decorated nanocarriers penetrating the blood-brain barrier for imaging and therapy of brain diseases.

Blood-Brain Barrier (BBB) is one of the most important physiological barriers strictly restricting the substance exchange between blood and brain tissues. While the BBB protects the brain from infections and toxins and maintains brain homeostasis, it is also recognized as the main obstacle to the penetration of therapeutics and imaging agents into the brain. Due to high specificity and affinity, peptides are frequently exploited to decorate nanocarriers across the BBB for diagnosis and/or therapy purposes.