Near-Infrared Responsive Membrane Nanovesicles Amplify Homologous Targeting Delivery of Anti-PD Immunotherapy against Metastatic Tumors.

The major obstacles of anti-PD therapy in metastatic tumors are limited drug delivery in primary tumors and metastatic foci, and the lack of tumor-infiltrating lymphocytes (TILs). Here, the authors constructed a novel cellular membrane nanovesicles platform (M/IR NPs) based on homologous targeting and near-infrared (NIR) responsive release strategy to potentiate PD-1/PD-L1 blockade therapy against metastatic tumors. In tumor-bearing mice, biomimetic M/IR NPs targeted both primary tumors and their lung metastases.

Thermal-sensitive lipid nanoparticles potentiate anti-PD therapy through enhancing drug penetration and T lymphocytes infiltration in metastatic tumor.

The response rate of anti-PD therapy in most cancer patients remains low. Therapeutic drug and tumor-infiltrating lymphocytes (TILs) are usually obstructed by the stromal region within tumor microenvironment (TME) rather than distributed around tumor cells, thus unable to induce the immune response of cytotoxic T cells. Here, we constructed the cationic thermosensitive lipid nanoparticles IR780/DPPC/BMS by introducing cationic NIR photosensitizer IR-780 iodide (IR780) modified lipid components, thermosensitive lipid DPPC and PD-1/PD-L1 inhibitor BMS202 (BMS).

Quercetin Covalently Linked Lipid Nanoparticles: Multifaceted Killing Effect on Tumor Cells.

The encapsulation of hydrophobic drugs is a problem that many researchers are working on. The goal of this study is to achieve the delivery of hydrophobic drugs by means of prodrugs and nanoformulations for a stronger tumor cell-killing effect and explore related killing mechanisms. Lipophilic quercetin (Qu) was covalently linked to glyceryl caprylate-caprate (Gcc) via disulfide bonds-containing 3,3'-dithiodipropionic acid (DTPA) to synthesize novel lipid Qu-SS-Gcc.

Correction: A novel biocompatible, simvastatin-loaded, bone-targeting lipid nanocarrier for treating osteoporosis more effectively.

[This corrects the article DOI: 10.1039/D0RA00685H.].

A novel biocompatible, simvastatin-loaded, bone-targeting lipid nanocarrier for treating osteoporosis more effectively.

An insufficient drug concentration at the target site and drug efflux resulting in poor efficacy are recognized as important obstacles in osteoporosis treatment. Simvastatin (SIM), which can treat osteoporosis by promoting osteoblast differentiation and mineralization through the bone morphogenetic proteins (BMP)-Smad signaling pathway, has lower bioavailability, and less bone tissue distribution. Herein, novel lipid nanoparticles (LNPs) delivering SIM (SIM/LNPs) for osteoporosis therapy were developed with aspartic oligopeptide (ASP , here ASP)-based bone-targeting moieties grafted to the nanoparticles (SIM/ASP-LNPs) in an attempt to increase the concentration of SIM in bones with a relatively low dose to minimize adverse effects.

Inhibition of chemotherapy-related breast tumor EMT by application of redox-sensitive siRNA delivery system CSO-ss-SA/siRNA along with doxorubicin treatment.

Metastasis is one of the main reasons causing death in cancer patients. It was reported that chemotherapy might induce metastasis. In order to uncover the mechanism of chemotherapy-induced metastasis and find solutions to inhibit treatment-induced metastasis, the relationship between epithelial-mesenchymal transition (EMT) and doxorubicin (DOX) treatment was investigated and a redox-sensitive small interfering RNA (siRNA) delivery system was designed.

Chitosan-modified lipid nanodrug delivery system for the targeted and responsive treatment of ulcerative colitis.

Targeted and sensitive drug release at the colitis site is critical for the effective therapy of ulcerative colitis and reduction of side effects from the drug. Herein, we used 3,3'-dithiodipropionic acid (DTPA) to covalently link quercetin (Qu) and glyceryl caprylate-caprate (Gcc) via ester bonds to prepare Qu-SS-Gcc lipid nanoparticles (Qu-SS-Gcc LNPs). Dexamethasone (Dex) was used as a model drug, and chitosan (CSO) was modified on the surface of Qu-SS-Gcc LNPs to obtain CSO-modified Dex-loaded Qu-SS-Gcc LNPs (CSO/Dex/LNPs).

Redox-responsive chitosan oligosaccharide-SS-Octadecylamine polymeric carrier for efficient anti-Hepatitis B Virus gene therapy.

DrzBC and DrzBS (10-23 DNAzyme) could block the expression of HBV e- and s- gene respectively. But the application of 10-23 DNAzyme was limited owing to the lack of appropriate delivery vehicles. Chitosan oligosaccharide-SS-Octadecylamine (CSSO), a redox-responsive nano-sized polymeric carrier, could self-aggregate and bind with DNA by electrostatic interaction at proper mass ratio.

Rational Design of Redox-Responsive and P-gp-Inhibitory Lipid Nanoparticles with High Entrapment of Paclitaxel for Tumor Therapy.

An insufficient drug concentration at the target site and drug efflux resulting in poor efficacy is recognized as important obstacles in tumor treatment. Herein, novel lipid nanoparticles (LNPs) with redox-responsive properties based on disulfide bond-contained, quercetin (Qu)-grafted glyceryl caprylate-caprate (Gcc) are introduced (Qu-SS-Gcc LNPs). Qu-SS-Gcc LNPs show good entrapment of paclitaxel (PTX) due to π-π stacking between the aromatic rings of Qu and PTX.

Studies on Chemical Reactivity and Electrocatalysis of Two Acylmethyl(hydroxymethyl)pyridine Ligand-Containing [Fe]-Hydrogenase Models (2-COCH-6-HOCHCHN)Fe(CO)L (L = η-SCOMe, η-2-SCHN).

On the basis of preparation and characterization of [Fe]-Hase models (2-COCH-6-HOCHCHN)Fe(CO)L (A, L = η-SCOMe; B, L = η-2-SCHN), the chemical reactivities of A and B with various electrophilic and nucleophilic reagents have been investigated, systematically. Thus, when A reacted with 1 equiv of MeCOCl in the presence of EtN in MeCN to give the η-SCOMe-coordinated acylation product (2-COCH-6-MeCOCHCHN)Fe(CO)(η-SCOMe) (1), treatment of A with excess HBF·EtO in MeCN gave the cationic MeCN-coordinated complex [(2-COCH-6-HOCHCHN)Fe(CO)(MeCN)](BF) (2). In addition, when 2 was treated with 1 equiv of 2,6-(p-4-MeCH)CHSK or PPh in CHCl to give the thiophenolato- and PPh-substituted derivatives (2-COCH-6-HOCHCHN)Fe(CO)[2,6-(p-MeCH)CHS] (3) and [(2-COCH-6-HOCHCHN)Fe(CO)(PPh)](BF) (4), treatment of B with 1 equiv of PMe or P(OMe) in THF afforded the phosphine- and phosphite-substituted complexes (2-COCH-6-HOCHCHN)(η-2-SCHN)Fe(CO)L (5, L = PMe; 6, L = P(OMe)).

Low molecular weight polyethylenimine-conjugated gold nanospheres: a platform for selective gene therapy controlled by near-infrared light.

Aim: Whether PEI-HAuNS could promote gene transfection efficiency controlled by near-infrared (NIR) light.

Materials & Methods: This safe nonviral gene delivery system was obtained by conjugating low molecular weight (2 kDa) polyethylenimine (PEI) onto hollow gold nanospheres (PEI-HAuNS). Upon NIR laser irradiation, there was a conspicuous increase both in the in vitro and in vivo transfection achieved by the nanocomplexes.

Transport Mechanisms of Solid Lipid Nanoparticles across Caco-2 Cell Monolayers and their Related Cytotoxicology.

Solid lipid nanoparticles (SLNs) have been extensively investigated and demonstrated to be a potential nanocarriers for improving oral bioavailability of many drugs. However, the molecular mechanisms related to this discovery are not yet understood. Here, the molecular transport mechanisms of the SLNs crossing simulative intestinal epithelial cell monolayers (Caco-2 cell monolayers) were studied.

Tetracycline-grafted PLGA nanoparticles as bone-targeting drug delivery system.

Purpose: Nanoparticles (NPs) that target bone tissue were developed using poly(lactic-co-glycolic acid) (PLGA) copolymers and tetracycline (TC)-based bone-targeting moieties. These NPs are expected to enable the transport of drugs, such as simvastatin (SIM), for the treatment of osteoporosis.

Methods: The molecular structures of TC-PLGA were validated by (1)H-NMR, and the SIM-loaded NPs were prepared using the solvent emulsification method.

High efficiency intracellular transport of cationic peptide stearate for gene delivery in tumor cells and multipotent stem cells.

Identifying an optimal gene vector is critical for improving transfection efficiency in gene therapy. In this study, a novel, non-viral gene vector composed of a stearate cationic peptide, Cys-Arg-His-Lys-Arg-His-Lys-Arg-His-Lys-Arg-His (CRHKRHKRHKRH), was engineered. The stearate cationic peptide (STR-Pep) could form micelles via its amphipathic properties at a concentration of 182 μg/mL, and condense plasmid DNA effectively above weight ratio of 1:1 to form nanosize complex nanoparticles.

Selective redox-responsive drug release in tumor cells mediated by chitosan based glycolipid-like nanocarrier.

The redox responsive nanocarriers have made a considerable progress in achieving triggered drug release by responding to the endogenous occurring difference between the extra- and intra- cellular redox environments. Despite the promises, this redox difference exists both in normal and tumor tissue. So a non-selective redox responsive drug delivery system may result in an undesired drug release in normal cells and relevant side-effects.

High tolerated paclitaxel nano-formulation delivered by poly (lactic-co-glycolic acid)-g-dextran micelles to efficient cancer therapy.

Unlabelled: The amphiphilic graft copolymer poly (lactic-co-glycolic acid)-g-dextran (Dex-PLGA) was successfully synthesized to fabricate micelles for the delivery of paclitaxel with low critical micelle concentration (CMC). The sizes of paclitaxel-loaded Dex-PLGA (Dex-PLGA/PTX) micelles were kept below 100nm with a relatively narrow size distribution. This novel PTX nano-formulation was found to exhibit slightly stronger in vitro cytotoxicity against SKOV-3, OVCAR-8 and MCF-7 cells with Taxol®.

Specific targeting of A54 homing peptide-functionalized dextran-g-poly(lactic-co-glycolic acid) micelles to tumor cells.

The delivery of chemotherapeutics into tumor cells is a fundamental knot for tumor-target therapy to improve the curative effect and avoid side effects. Here, A54 peptide-functionalized poly(lactic-co-glycolic acid)-grafted dextran (A54-Dex-PLGA) was synthesized. The synthesized A54-Dex-PLGA self-assembled to form micelles with a low critical micelle concentration of 16.

Effect of anionic PEGylated polypeptide on gene transfection mediated by glycolipid conjugate micelles.

To improve the gene transfection efficiency mediated by chitosan-g-stearic acid (CS) micelles, poly(ethylene glycol)-b-poly(γ-glutamic acid) (PG) was incorporated into a CS-based gene delivery system. CS/PG/pDNA complexes were prepared by ionic interaction. CS and PEGylated CS (PCS) micelles were introduced to prepare binary complexes for use as controls.

TNYL peptide functional chitosan-g-stearate conjugate micelles for tumor specific targeting.

Nowadays, a real challenge in cancer therapy is to design drug delivery systems that can achieve high concentrations of drugs at the target site for improved therapeutic effect with reduced side effects. In this research, we designed and synthesized a homing peptide-(TNYLFSPNGPIA, TNYL) modified chitosan-g-stearate (CS) polymer micelle (named T-CS) for targeting delivery. The peptide displayed specific binding affinity to EphB4 which is a member of the Eph family of receptor tyrosine protein kinases.

Transport pathways of solid lipid nanoparticles across Madin-Darby canine kidney epithelial cell monolayer.

An understanding of drug delivery system transport across epithelial cell monolayer is very important for improving the absorption and bioavailability of the drug payload. The mechanisms of epithelial cell monolayer transport for various nanocarriers may differ significantly due to their variable components, surface properties, or diameter. Solid lipid nanoparticles (SLNs), conventionally formed by lipid materials, have gained increasing attention in recent years due to their excellent biocompatibility and high oral bioavailability.

Efficient gene delivery system mediated by cis-aconitate-modified chitosan-g-stearic acid micelles.

Cis-aconitate-modified chitosan-g-stearic acid (CA-CSO-SA) micelles were synthesized in this study to improve the gene transfection efficiency of chitosan-g-stearic acid (CSO-SA). The CA-CSO-SA micelles had a similar size, critical micelle concentration, and morphology, but their zeta potential and cytotoxicity were reduced compared with CSO-SA micelles. After modification with cis-aconitate, the CA-CSO-SA micelles could also compact plasmid DNA (pDNA) to form nanocomplexes.

Synthesis, structural characterization, and some properties of 2-acylmethyl-6-ester group-difunctionalized pyridine-containing iron complexes related to the active site of [Fe]-hydrogenase.

As biomimetic models for [Fe]-hydrogenase, the 2-acylmethyl-6-ester group-difunctionalized pyridine-containing iron(II) complexes 1-4 have been successfully prepared via the following three separate steps. In the first step, the acylation or esterification of difunctionalized pyridine 2-(p-MeC6H4SO3CH2)-6-HOCH2C5H3N with acetyl chloride or benzoic acid gives the corresponding pyridine derivatives 2-(p-MeC6H4SO3CH2)-6-RCO2CH2C5H3N (A, R = Me; B, R = Ph). The second step involves reaction of A or B with Na2Fe(CO)4 followed by treatment of the intermediate Fe(0) complexes [Na(2-CH2-6-RCO2CH2C5H3N)Fe(CO)4] (M1, R = Me; M2, R = Ph) with iodine to afford 2-acylmethyl-6-acetoxymethyl or 6-benzoyloxymethyl-difunctionalized pyridine-containing Fe(II) iodide complexes [2-C(O)CH2-6-RCO2CH2C5H3N]Fe(CO)2I (1, R = Me; 3, R = Ph).

A novel subcutaneous infusion delivery system based on osmotic pump: in vitro and in vivo evaluation.

An economical, convenient portable drug delivery system combining osmotic pump with subcutaneous infusion was developed, which was composed of three primary components: water chamber, osmotic pump chamber and support base. Ceftriaxone sodium (CRO) was selected as the model drug and osmotic pump tablets were prepared. The influence of osmotic agents on drug release profiles was evaluated.

Preparation and characteristics of lipid nanoemulsion formulations loaded with doxorubicin.

Purpose: Safe and effective lipid nanoemulsion (LNE) formulations for the antitumor delivery of doxorubicin is designed.

Methods: LNEs composed of medium-chain triglyceride, soybean oil, lecithin, and doxorubicin are prepared by a solvent-diffusion method in an aqueous system. The effects of lipid material composition and polyethylene glycol (PEG)ylation on the size, drug encapsulation efficiency, and stability of LNEs are investigated.

Ternary nanoparticles composed of cationic solid lipid nanoparticles, protamine, and DNA for gene delivery.

Background: The objective of this research was to design an effective gene delivery system composed of cationic solid lipid nanoparticles (SLNs), protamine, and Deoxyribonucleic acid DNA.

Methods: Cationic SLNs were prepared using an aqueous solvent diffusion method with octadecylamine as the cationic lipid material. First, protamine was combined with DNA to form binary protamine/DNA nanoparticles, and the ternary nanoparticle gene delivery system was then obtained by combining binary protamine/DNA nanoparticles with cationic SLNs.