Delivery of quercetin for breast cancer and targeting potentiation via hyaluronic nano-micelles.

Quercetin (QT) is a very effective anticancer drug in combating breast cancer. However, it has several disadvantages such as poor water solubility, low bioavailability and low targeting, which seriously restrict its clinical application. In this work, amphiphilic hyaluronic acid polymers (dHAD) were synthesized by grafting dodecylamine to hyaluronic acid (HA).

Combination of 7--geranylquercetin and microRNA-451 enhances antitumor effect of Adriamycin by reserving P-gp-mediated drug resistance in breast cancer.

Although there are a lot of chemical drugs to treat breast cancer, increasing drug resistance of cancer cells has strongly hindered the effectiveness of chemotherapy. ATP-binding cassette transporters represented by P-glycoprotein (P-gp), multidrug resistance associated protein 1 (MRP1) and breast cancer resistance protein (BCRP) play an important role in drug resistance. This study aims to investigate the effect of 7--geranylquercetin (GQ) combining microRNA-451(miR-451) on reversing drug resistance of breast cancer and reveal the mechanism related to P-gp.

pH-sensitive, tail-modified, ester-linked ionizable cationic lipids for gene delivery.

Ionizable cationic lipids have great potential for gene delivery, yet the effect of the molecular structure of such lipids on gene delivery efficiency is an ongoing research challenge. To better understand corresponding structure-function activity relationships, we synthesized four ester-linked, pH-responsive, ionizable cationic lipids. The screened DEDM4 lipid, containing 2-ethylenedimethylamine in the headgroup and a branched-chain tail, exhibited a high delivery efficacy of plasmid DNA and siRNA in A549 cells, which was comparable with that of the commercial reagent lipofectamine 3000 (lipo3000).

Cationic Nanoparticulate System for Codelivery of MicroRNA-424 and Podophyllotoxin as a Multimodal Anticancer Therapy.

Because of the complexity of cancer ecosystems, the efficacy of single-agent chemotherapy is limited. Herein, we report the use of cationic nanoparticles (designated PPCNs) generated from a chemically modified form of the chemotherapeutic agent podophyllotoxin (PPT) to deliver both microRNA-424 (miR-424) and PPT to tumor cells, thus combining chemotherapy and gene therapy. We evaluated the optimal loading ratio of miR-424─which targets programmed cell death ligand 1 (PD-L1) mRNA and reduces PD-L1 production, thus promoting the attack of tumor cells by T cells─for effective delivery of miR-424 and PPCNs into nonsmall-cell lung cancer cells (H460).

pH/reduction dual-responsive hyaluronic acid-podophyllotoxin prodrug micelles for tumor targeted delivery.

Polymer-based prodrug nanocarriers with tumor-targeting and controlled-release properties are in great demand for enhanced cancer treatment. Hyaluronic acid (HA), which has excellent biocompatibility and targeting ability for cluster determinant 44 (CD44), has been proposed for delivering drugs that have poor solubility and high toxicity. Herein, podophyllotoxin (PPT) was conjugated to HA via ester and disulfide linkages to construct a pH- and reduction-responsive prodrug (HA-S-S-PPT).

Self-Assembly of Podophyllotoxin-Loaded Lipid Bilayer Nanoparticles for Highly Effective Chemotherapy and Immunotherapy via Downregulation of Programmed Cell Death Ligand 1 Production.

Low drug delivery efficiency elevates the cost of medication, lowers the therapeutic efficacy, and appears as a leading reason for unmet needs in anticancer therapies. Herein, we report the development of self-assembled podophyllotoxin-loaded lipid bilayer nanoparticles that inhibit the production of programmed cell death ligand 1 in lung cancer cells and promote tumor-specific immune responses, thus offering a strategy for regulating the immunosuppressive microenvironment of tumors. In addition, encapsulation of podophyllotoxin in the nanoparticles reduced its systemic toxicity, enhanced its penetration into tumors, and increased its antitumor efficacy.

Paclitaxel loading in cationic liposome vectors is enhanced by replacement of oleoyl with linoleoyl tails with distinct lipid shapes.

Lipid carriers of hydrophobic paclitaxel (PTX) are used in clinical trials for cancer chemotherapy. Improving their loading capacity requires enhanced PTX solubilization. We compared the time-dependence of PTX membrane solubility as a function of PTX content in cationic liposomes (CLs) with lipid tails containing one (oleoyl; DOPC/DOTAP) or two (linoleoyl; DLinPC/newly synthesized DLinTAP) cis double bonds by using microscopy to generate kinetic phase diagrams.

Temperature-Sensitive Lipid-Coated Carbon Nanotubes for Synergistic Photothermal Therapy and Gene Therapy.

The combination of photothermal therapy (PTT) and gene therapy (GT) shows great potential to achieve synergistic anti-tumor activity. However, the lack of a controlled release of genes from carriers remains a severe hindrance. Herein, peptide lipid (PL) and sucrose laurate (SL) were used to coat single-walled carbon nanotubes (SCNTs) and multi-walled carbon nanotubes (MCNTs) to form bifunctional delivery systems (denoted SCNT-PS and MCNT-PS, respectively) with excellent temperature-sensitivity and photothermal performance.

Integrin αβ-targeted liposomal drug delivery system for enhanced lung cancer therapy.

Conventional chemotherapy for tumor treatment remains flawed because it fails to limit cytotoxicity to a small set of selectable tissues. Active targeting techniques for the delivery of drugs to specific sites are increasingly used to enhance drug accumulation at tumor sites with the aim of reducing side effects in vivo. Liposomes, modified with different targeting ligands, are considered to be one of the most promising targeted drug carriers.

Targeted-delivery of siRNA via a polypeptide-modified liposome for the treatment of gp96 over-expressed breast cancer.

Targeted gene therapy has led to significant breakthroughs in cancer treatment. Heat shock protein gp96 is an emerging target for tumor treatment because of its transfer ability from reticulum to tumor cell surface. CDO14 is a peptide cationic liposome developed in our laboratory with higher gene transfection efficiency and lower toxicity compared with the existing cationic liposomes.

Application of CRISPR/Cas9 System to Reverse ABC-Mediated Multidrug Resistance.

Multidrug resistance (MDR) is the main obstacle in cancer chemotherapy. ATP-binding cassette (ABC) transporters can transport a wide range of antitumor drugs out of cells, which is the most common reason in the development of resistance to drugs. Currently, various therapeutic strategies are used to reverse MDR, among which CRISPR/Cas9 gene editing technique is expected to be an effective way.

Co-delivery of paclitaxel and anti-VEGF siRNA by tripeptide lipid nanoparticle to enhance the anti-tumor activity for lung cancer therapy.

The combination of chemotherapeutic drug paclitaxel (PTX) and VEGF siRNA could inhibit cancer development with synergistic efficacy. However, efficient and safe delivery systems with high encapsulation efficiency of PTX and a long-time release of drugs are urgently needed. In this study, novel nanoparticles (PTX/siRNA/FALS) were constructed by using tripeptide lipid (L), sucrose laurate (S), and folate-PEG-DSPE (FA) to co-deliver PTX and siRNA.

Stimuli-Responsive Polysaccharide Enveloped Liposome for Targeting and Penetrating Delivery of survivin-shRNA into Breast Tumor.

Silencing the inhibitor of apoptosis (IAP) by RNAi is a promising method for tumor therapy. One of the major challenges lies in how to sequentially overcome the system barriers in the course of the tumor targeting delivery, especially in the tumor accumulation and penetration. Herein we developed a novel stimuli-responsive polysaccharide enveloped liposome carrier, which was constructed by layer-by-layer depositing redox-sensitive amphiphilic chitosan (CS) and hyaluronic acid (HA) onto the liposome and then loading IAP inhibitor survivin-shRNA gene and permeation promoter hyaluronidase (HAase) sequentially.

7-O-geranylquercetin contributes to reverse P-gp-mediated adriamycin resistance in breast cancer.

Aims: To investigate the effect of 7-O-geranylquercetin (GQ), a derivative of quercetin (Q), on reversing drug resistance in breast cancer MCF-7/ADR cells and reveal the mechanisms related to P-glycoprotein (P-gp).

Main Methods: Cell viability was determined by MTT assay. Accumulation of adriamycin (ADR) in cells was determined by confocal fluorescence microscope and microplate reader while that of rhodamine (Rh) was measured by flow cytometry.

Metabolic profile and structure-activity relationship of resveratrol and its analogs in human bladder cancer cells.

Resveratrol (RV), a promising anti-cancer candidate, is limited in application for its poor bioavailability. However, the better bioavailability has been found in some RV derivatives. So in this paper, we explore the structure-activity relationship and the metabolic profiles of RV and its analogs (polydatin [PD], oxyresveratrol [ORV], acetylresveratrol [ARV]) in human bladder cancer T24 cells, and then evaluate their active forms and key chemical functional groups which may determine the fate of tumor cells.

Synergistic effects of 7-O-geranylquercetin and siRNAs on the treatment of human breast cancer.

Aims: To investigate the antitumor effect of 7-O-geranylquercetin (GQ) combining with survivin siRNA (siSuvi) or IL-10 siRNA (siIL-10) to breast cancer.

Main Methods: Xenograft tumor model was established by subcutaneously inoculating human breast cancer MCF-7 cells in BALB/c nude mice. Transfection efficiency of siRNA mediated by cationic liposome CDO14 in MCF-7 cells and tumor bearing mice was measured by flow cytometer and living imaging sysytem, respectively.

Toxicological exploration of peptide-based cationic liposomes in siRNA delivery.

The toxicology of cationic liposomes was explored to advance clinical trials of liposome-mediated gene therapy through the analysis of a peptide cationic liposome with DOTAP as a positive control. We first investigated the delivery of luciferase siRNA by several peptide liposomes in mice bearing lung cancer A549 cell xenografts. Of these, a cationic liposome (CDO14) was selected for further investigation.

Zwitterionic pH-responsive hyaluronic acid polymer micelles for delivery of doxorubicin.

As zwitterionic polymers show great promise in drug delivery, hyaluronic acid (HA) was deacetylated and grafted with dodecylamine to prepare a pH-sensitive zwitterionic polymer dHAD used as a carrier for antitumor drugs. The polymer was negatively charged at pH 7.4 and became positive at pH 6.

Dual stimuli-responsive saccharide core based nanocarrier for efficient Birc5-shRNA delivery.

Stimuli-responsive delivery systems show great promise in meeting the requirements of several delivery stages to achieve satisfactory gene transfection. This report describes a novel stimuli-responsive nanocarrier consisting of a dual stimuli-responsive chitosan (SCS) core and a polyethyleneimine (PEI) and polyethylene glycol (PEG) corona. The SCS core was constructed by cross-linking bio-safe chitosan saccharide via pH-sensitive hydrazone bonds and redox-sensitive disulfide bonds, which conferred the nanocarrier with a dual stimuli-responsive property.

Orthogonal test design for optimization of the extraction of essential oil from var. and evaluation of its antibacterial activity against periodontal pathogens.

The optimum extraction conditions of essential oil from var. applied by an orthogonal L(3) test were a water-to-raw material ratio of 17, a particle size of  ≤ 3.8 mm and an extraction time of 2 h.

Effects of sucrose ester structures on liposome-mediated gene delivery.

Unlabelled: Sucrose esters (SEs) have great potential applications in gene delivery because of their low toxicity, excellent biocompatibility, and biodegradability. By using tripeptide-based lipid (CDO) as a model lipid and SEs as helper lipids, a series of liposomes were prepared. The SEs with hydrophilic-lipophilic balance (HLB) values of 1, 6, 11, or 16 and the fatty acids of laurate, stearate, or oleate were used in the liposomes.

PP2A as the Main Node of Therapeutic Strategies and Resistance Reversal in Triple-Negative Breast Cancer.

Triple negative breast cancer (TNBC), is defined as a type of tumor lacking the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). The ER, PR and HER2 are usually the molecular therapeutic targets for breast cancers, but they are ineffective for TNBC because of their negative expressions, so chemotherapy is currently the main treatment strategy in TNBC. However, drug resistance remains a major impediment to TNBC chemotherapeutic treatment.

Effects of specific egg yolk immunoglobulin on pan-drug-resistant Acinetobacter baumannii.

With the growing emergence of pan-drug-resistant Acinetobacter baumannii (PDR-Ab) strains in clinical, new strategies for the treatment of PDR-Ab infections are urgently needed. Egg yolk immunoglobulin (IgY) as a convenient and inexpensive antibody has been widely applied to the therapy of infectious diseases. The aim of this study was to produce IgY specific to PDR-Ab and investigate its antibacterial effects in vitro and in vivo.