Self-Adjuvant Effect by Manipulating the Bionano Interface of Liposome-Based Nanovaccines.

Nanovaccines are of increasing scrutiny due to their plasticity in size, composition, and surface properties to enhance antigenicity. However, inevitable absorption of plasma proteins affects the fate of nanovaccines by reshaping biological identity. Herein IgM was validated as a self-adjuvant by regulating antigen-presenting cells recognition of liposome-based nanovaccines.

Unraveling GLUT-mediated transcytosis pathway of glycosylated nanodisks.

Glucose transporter (GLUT)-mediated transcytosis has been validated as an efficient method to cross the blood-brain barrier and enhance brain transport of nanomedicines. However, the transcytosis process remains elusive. Glycopeptide-modified nanodisks (Gly-A7R-NDs), which demonstrated high capacity of brain targeting via GLUT-mediated transcytosis in our previous reports, were utilized to better understand the whole transcytosis process.

A pentapeptide enabled AL3810 liposome-based glioma-targeted therapy with immune opsonic effect attenuated.

AL3810, a molecular dual inhibitor of the vascular endothelial growth factor receptor (VEGFR) and fibroblast growth factor receptor (FGFR), has earned the permission of phase II clinical trial for tumor treatment by China FDA. As a reversible ATP-competitive inhibitor, AL3810 targets ATP-binding site on intracellular region of VEGFR and FGFR, whereas, AL3810 lacking interplay with extracellular region of receptors rendered deficient blood-brain tumor barrier (BBTB) recognition, poor brain penetration and unsatisfactory anti-glioma efficacy. Integrin v3 overexpressed on capillary endothelial cells of BBTB as well as glioma cells illuminated ligand-modified liposomes for pinpoint spatial delivery into glioma.

Virus-mimetic systems for cancer diagnosis and therapy.

Over past decades, various strategies have been developed to enhance the delivery efficiency of therapeutics and imaging agents to tumor tissues. However, the therapeutic outcome of tumors to date have not been significantly improved, which can be partly attributed to the weak targeting ability, fast elimination, and low stability of conventional delivery systems. Viruses are the most efficient agents for gene transfer, serving as a valuable source of inspiration for designing nanoparticle-based delivery systems.

Interrogation of Folic Acid-Functionalized Nanomedicines: The Regulatory Roles of Plasma Proteins Reexamined.

Folic acid (FA) has been extensively exploited to facilitate targeted delivery of nanomedicines by recognizing the folate receptor-α (FR-α) overexpressed in many human cancers. Unfortunately, none have been approved for clinical use yet. Here we reveal that FA functionalization induces heavy natural IgM absorption on the liposomal surface, depriving FA of receptor recognition and accelerating complement activation .

Factors Influencing the Immunogenicity and Immunotoxicity of Cyclic RGD Peptide-Modified Nanodrug Delivery Systems.

c(RGDyK)-modified liposomes have been shown to be immunogenic and potentially trigger acute systemic anaphylaxis upon repeated intravenous injection in both BALB/c nude mice and ICR mice. However, questions concerning the potential influence of mouse strains, immunization routes, drug carrier properties, and changes in c(RGDyK) itself on the immunogenicity and resultant immunotoxicity (anaphylaxis) of cyclic RGD peptide-modified nanodrug delivery systems remain unanswered. Here, these potential impact factors were investigated, aiming to better understand the immunological properties of cyclic RGD peptide-based nanodrug delivery systems and seek for solutions for this immunogenicity-associated issue.

Guanidyl and imidazolyl integration group-modified PAMAM for gastric adenocarcinoma gene therapy.

Background: Gene therapy has become a potential strategy for cancer treatment. However, the development of efficient gene vectors restricts the application for cancer gene treatment. Functionalization of polymers with functional groups can significantly improve their transfection efficacy.

ɑβ-targeted liposomal drug delivery system with attenuated immunogenicity enabled by linear pentapeptide for glioma therapy.

Owing to the binding capacity to ɑβ integrin overexpressed on glioma, vasculogenic mimicry and neovasculature, the peptide c(RGDyK) has been exploited pervasively to functionalize nanocarriers for targeted delivery of bioactives. The former study in our group substantiated the immunotoxicity of c(RGDyK)-modified liposome, and this unfavorable immunogenicity is known to compromise blood circulation, targeting efficacy and therapeutic outcome. Therefore, we need to find a superior alternative ligand in order to evade the exquisite immuno-sensitization.

All-stage precisional glioma targeted therapy enabled by a well-designed D-peptide.

Uncontrollable cell proliferation and irreversible neurological damage make glioma one of the most deadly diseases in clinic. Besides the multiple biological barriers, glioma stem cells (GSCs) that are responsible for the maintenance and recurrence of tumor tissues also hinder the therapeutic efficacy of chemotherapy. Therefore, all-stage precisional glioma targeted therapy regimens that could efficiently deliver drugs to glioma cells and GSCs after overcoming multiple barriers have received increasing scrutiny.

Synergistic Antitumor Effects on Drug-Resistant Breast Cancer of Paclitaxel/Lapatinib Composite Nanocrystals.

Drug resistance presents serious difficulties for cancer treatment. A combination of paclitaxel (PTX) and lapatinib (LAPA) shows potentials in multiple drug resistant cancers in the clinic, but it is almost impossible to deliver these two drugs to the tumor at the same time with the best proportion by simple co-administration of the respective current formualtions for their different pharmacokinetic profiles. Here composite nanocrystals of PTX and LAPA (cNC) were designed with a ratio of 2:1 (/), which was their intracellular ratio at the best synergistic efficacy on a drug-resistant cancer cell line (MCF-7/ADR).

Natural IgM dominates in vivo performance of liposomes.

Prevalent deposition of plasma proteins on nano-surface alters the synthetic identity of liposomes in blood circulation. The key plasma protein(s) that can dominate in vivo fate of liposomes are of central importance for preclinical design and precise medication of liposome-based therapeutics. Herein, natural IgM, but not IgG, is identified to ubiquitously absorb on liposomal surface and takes the lead in complement activation of different species.

Deliver anti-PD-L1 into brain by p-hydroxybenzoic acid to enhance immunotherapeutic effect for glioblastoma.

In glioblastoma with typical immunosuppressive characteristics, immune checkpoint inhibitors treatment showed unsatisfactory clinical effects, attributable to the exclusion of antibodies by blood-brain barrier (BBB) to a large extent. Herein, a conjugate of anti-programmed death ligand 1 antibody (αPDL1) and the targeting moiety p-hydroxybenzoic acid (pHA) was designed to realize crossing BBB of antibody based on the dopamine receptor mediated transcytosis. Conjugation with pHA did not influence the binding affinity of αPDL1 with PD-L1 protein, thus maintaining the capability of PD pathway blockade.

Brain-targeted drug delivery by manipulating protein corona functions.

Protein corona presents a major obstacle to bench-to-bedside translation of targeted drug delivery systems, severely affecting targeting yields and directing unfavorable biodistribution. Corona-mediated targeting provides a new impetus for specific drug delivery by precisely manipulating interaction modes of functional plasma proteins on nano-surface. Here bio-inspired liposomes (SP-sLip) were developed by modifying liposomal surface with a short nontoxic peptide derived from Aβ that specifically interacts with the lipid-binding domain of exchangeable apolipoproteins.

Conjugation of haematopoietic stem cells and platelets decorated with anti-PD-1 antibodies augments anti-leukaemia efficacy.

Patients with acute myeloid leukaemia who relapse following therapy have few treatment options and face poor outcomes. Immune checkpoint inhibition, for example, by antibody-mediated programmed death-1 (PD-1) blockade, is a potent therapeutic modality that improves treatment outcomes in acute myeloid leukaemia. Here, we show that systemically delivered blood platelets decorated with anti-PD-1 antibodies (aPD-1) and conjugated to haematopoietic stem cells (HSCs) suppress the growth and recurrence of leukaemia in mice.

Enhanced Delivery of Imatinib into Vaginal Mucosa via a New Positively Charged Nanocrystal-Loaded in Situ Hydrogel Formulation for Treatment of Cervical Cancer.

The present study was carried out to investigate the potential of cationic functionalization on imatinib nanocrystals to improve the mucoadhesiveness and, thus, delivery to the lesion of cervicovaginal tumors. Amino-group-functionalized imatinib nanocrystals (NC@PDA-NH₂) were prepared with near-spheroid shape, nanoscale size distribution, positive zeta potential, and relatively high drug content with the aid of the polydopamine-coating technique. Efficient interaction between NC@PDA-NH₂ and mucin was proven by mucin adsorption which was related to the positive zeta-potential value of NC@PDA-NH₂ and the change in the size distribution on mixing of NC@PDA-NH₂ and mucin.

RGD-modified PEGylated paclitaxel nanocrystals with enhanced stability and tumor-targeting capability.

Nanocrystals has been constructed for insoluble drugs as a novel type of nanoscale drug delivery systems with high drug loading. How to prepare nanocrystals with good stability and tumor targeting capability is still challenging. This study was to modify paclitaxel nanocrystals with polyethylene glycol (PEG) for stabilization and RGD peptide for tumor targeting.

Liposomes with cyclic RGD peptide motif triggers acute immune response in mice.

Liposomes with peptides motifs have been widely applied for targeted delivery of anticancer drugs. However, few studies have questioned whether peptide modification on liposomes may induce serious toxicity associated with immune stimulation. Here, we report that display of a tumor targeting cyclic RGD peptide (e.

Remote-Loaded Platelet Vesicles for Disease-Targeted Delivery of Therapeutics.

The recent emergence of biomimetic nanotechnology has facilitated the development of next-generation nanodelivery systems capable of enhanced biointerfacing. In particular, the direct use of natural cell membranes can enable multivalent targeting functionalities. Herein, we report on the remote loading of small molecule therapeutics into cholesterol-enriched platelet membrane-derived vesicles for disease-targeted delivery.

Development of an LC-MS/MS-based assay to determine artemitin in rat plasma and its application in a pharmacokinetic study.

Artemitin, a significant flavonol compound existing in Laggera pterodonta (DC.) Benth., Artemisia rupestris L, etc.

Enhanced immunocompatibility of ligand-targeted liposomes by attenuating natural IgM absorption.

Targeting ligands are anticipated to facilitate the precise delivery of therapeutic agents to diseased tissues; however, they may also severely affect the interaction of nanocarriers with plasma proteins. Here, we study the immunocompatibility of brain-targeted liposomes, which inversely correlates with absorbed natural IgM. Modification of long, stable positively charged peptide ligands on liposomes is inclined to absorb natural IgM, leading to rapid clearance and enhanced immunogenicity.

Nanosizing Noncrystalline and Porous Silica Material-Naturally Occurring Opal Shale for Systemic Tumor Targeting Drug Delivery.

Opal shale, as a naturally occurring and noncrystalline silica material with porous structure, has the potential to be a drug delivery carrier. In this study, we obtained opal shale nanoparticles (OS NPs) through the techniques of ultrasonic emulsion and differential centrifugation. The OS NPs exhibited markedly lower cytotoxicity than crystalline mesoporous silica nanoparticles.

Enhanced glioma-targeting and stability of GICP peptide coupled with stabilized peptide A7R.

Malignant glioma is usually accompanied by vigorous angiogenesis to provide essential nutrients. An effective glioma targeting moiety should include excellent tumor-cell homing ability as well as good neovasculature-targeting efficiency, and should be highly resistant to enzyme degradation in the bloodstream. The phage display-selected heptapeptide, the glioma-initiating cell peptide (GICP), was previously reported as a ligand for the VAV3 protein (a Rho-GTPase guanine nucleotide exchange factor), which is mainly expressed on glioma cells; the stabilized heptapeptide A7R has been shown to be the ligand of both vascular endothelial growth factor receptor 2 (VEGFR2) and neuropilin-1 (NRP-1), and has demonstrated good neovasculature-targeting ability.

2-Aminoimidazole facilitates efficient gene delivery in a low molecular weight poly(amidoamine) dendrimer.

Functional groups have shown great potential in gene delivery. However, a number of the reported functional groups can only overcome one certain physiological barrier, resulting in limited transfection efficiencies. Based on the structure-activity relationships of both imidazolyl and guanidyl, we designed a novel multifunctional group, 2-aminoimidazole (AM), for gene delivery.

Myristic Acid-Modified A7R Peptide for Whole-Process Glioma-Targeted Drug Delivery.

The clinical treatment of aggressive glioma has been a great challenge, mainly because of the complexity of the glioma microenvironment and the existence of the blood-brain tumor barrier (BBTB)/blood-brain barrier (BBB), which severely hampers the effective accumulation of most therapeutic agents in the glioma region. Additionally, vasculogenic mimicry (VM), angiogenesis, and glioma stem cells (GSC) in malignant glioma also lead to the failure of clinical therapy. To address the aforementioned issues, a whole-process glioma-targeted drug delivery strategy was proposed.