Hyperbranched lipoid-based lipid nanoparticles for bidirectional regulation of collagen accumulation in liver fibrosis.

Liver fibrosis leads to over one million deaths annually worldwide. Hepatic stellate cells (HSCs) have been identified as the main executors of liver fibrosis. Unfortunately, no drug has yet been approved for clinical use against liver fibrosis, largely because the tested drugs have been unable to access HSCs and efficiently remove the collagen accumulation involved in fibrogenesis.

Extracellular matrix-penetrating nanodrill micelles for liver fibrosis therapy.

As hepatic stellate cells (HSCs) are essential for hepatic fibrogenesis, HSCs targeted nano-drug delivery system is a research hotspot in liver fibrosis therapy. However, the excessive deposition of fibrosis collagen (mainly collagen I) in the space of Disse associated with hepatic fibrogenesis would significantly hinder nano-formulation delivery to HSCs. Here, we have prepared a collagenase I and retinol co-decorated polymeric micelle that possess nanodrill-like and HSCs-target function based on poly-(lactic-co-glycolic)-b-poly (ethylene glycol)-maleimide (PLGA-PEG-Mal) (named CRM) for liver fibrosis therapy.

A new strategy for hydrophobic drug delivery using a hydrophilic polymer equipped with stacking units.

A highly hydrophilic polymer equipped with guanidinium groups was used to load aromatic ring-containing hydrophobic agent doxorubicin (DOX) via π-π interaction. The results have shown that the delivery system exhibited enhanced cellular uptake and antitumor efficiency compared with free drugs. This study opens new avenues for the application of hydrophilic polymers in drug delivery.

Regulating the Golgi apparatus by co-delivery of a COX-2 inhibitor and Brefeldin A for suppression of tumor metastasis.

Finding a cure for breast cancer currently remains a medical challenge in due to the failure of common treatment methods to inhibit invasion and metastasis of cancer cells, which eventually leads to recurrence of breast cancer. Many secreted proteins are overexpressed and play crucial roles in tumorigenesis and development. The Golgi apparatus is a key protein processing and secretion factory in which metastasis-associated proteins are modified, transported and secreted; thus, regulating the Golgi apparatus of tumor cells is a viable strategy to inhibit tumor metastasis.

Vitamin A-decorated biocompatible micelles for chemogene therapy of liver fibrosis.

Liver fibrosis refers to excessive accumulation of hepatic collagen, which is primarily produced by activated hepatic stellate cells (HSCs). No effective drugs are clinically available to treat this condition, reflecting the fact that antifibrotic drugs do not specifically target activated HSCs. Here, we report the synthesis and evaluation of poly (lactide-co-glycolide)-polyspermine-poly (ethylene glycol)-vitamin A (PLGA-PSPE-PEG-VA), and activated HSC-targeted, biocompatible amphiphilic polymers for co-delivery of chemical (silibinin) and genetic (siCol1α1) drugs that synergistically suppress collagen I accumulation in fibrogenesis.

Biocompatible fluorinated poly(β-amino ester)s for safe and efficient gene therapy.

Cationic polymers have been widely used as one of the most promising non-viral vehicles for gene delivery due to their potential safety and ease of large-scale production. Here, we report the design and synthesis of a series of novel biodegradable fluorinated poly(β-amino ester)s (FPBAEs) by simple Michael-addition reaction as safe and efficient gene carrier. The results of transfection efficacy assay demonstrated the optimal FPBAE could mediated much higher GFP expression than the commercial transfection agents, polyethyleneimine (PEI, M = 25K) and Lipo 2000, as well as the non-fluorinated poly(β-amino ester)s (PBAE) on both HeLa and HEK-293T cell lines (higher than 70 and 90%, respectively), which was largely attributed to fluorination.

pH-Responsive de-PEGylated nanoparticles based on triphenylphosphine-quercetin self-assemblies for mitochondria-targeted cancer therapy.

We have developed mitochondria-targeted self-assembled nanoparticles (NPs) based on amphiphilic triphenylphosphine-quercetin (TPP-Que) conjugates, which were further modified by poly(ethylene glycol) via a pH-responsive coordination bond to form TQ-PEG NPs. And it is revealed that the TQ-PEG NPs were more effective therapeutic agents compared with Que in vitro and in vivo.

MnO-Based Nanoplatform Serves as Drug Vehicle and MRI Contrast Agent for Cancer Theranostics.

Multidrug resistance (MDR) greatly impedes the therapeutic efficacy of chemotherapeutic agents. Overexpression of ATP-binding cassette (ABC) transporters, such as P-gp, on the surface of tumor cells is a major mechanism in MDR. In this study, we fabricated manganese dioxide (MnO)/doxorubicin (DOX)-loaded albumin nanoparticles (BMDN) for magnetic resonance imaging and reversing MDR in resistant tumor.

Curcumin-coordinated nanoparticles with improved stability for reactive oxygen species-responsive drug delivery in lung cancer therapy.

Background: The natural compound curcumin (Cur) can regulate growth inhibition and apoptosis in various cancer cell lines, although its clinical applications are restricted by extreme water insolubility and instability. To overcome these hurdles, we fabricated a Cur-coordinated reactive oxygen species (ROS)-responsive nanoparticle using the interaction between boronic acid and Cur.

Materials And Methods: We synthesized a highly biocompatible 4-(hydroxymethyl) phenylboronic acid (HPBA)-modified poly(ethylene glycol) (PEG)-grafted poly(acrylic acid) polymer (PPH) and fabricated a Cur-coordinated ROS-responsive nanoparticle (denoted by PPHC) based on the interaction between boronic acid and Cur.

Transferrin-inspired vehicles based on pH-responsive coordination bond to combat multidrug-resistant breast cancer.

A novel biomimetic drug delivery system (BDDS) inspired by the pH-dependent ferric ion-transport and release manner of transferrin (Tf) was developed for combating multidrug-resistant breast cancer. Tf-inspired carrier was synthesized by modifying bovine serum albumin (BSA) with histamine (HA) through amide reaction to provide superior specific coordination sites for ferric ion-drug complexes, and self-assembled into nanoparticles (NPs) induced by coordination bond. Tf-inspired NPs were prepared via environment-friendly method, and well redispersed in saline after lyophilization.

One-step assembly of polymeric demethylcantharate prodrug/Akt1 shRNA complexes for enhanced cancer therapy.

This report demonstrated a one-step assembly for co-delivering chemotherapeutics and therapeutic nucleic acids, constructed by integrating drug molecules into a nucleic acid condensing polymeric prodrug through degradable linkages. Demethylcantharate was selected as the model drug and pre-modified by esterifying its two carboxylic groups with 2-hydroxyethyl acrylate. The synthesized demethylcantharate diacrylate was then used to polymerize with linear polyethyleneimine (PEI 423) through a one-step Michael-addition reaction.

Aerosol delivery of folate-decorated hyperbranched polyspermine complexes to suppress lung tumorigenesis via Akt signaling pathway.

Lung cancer has been a leading cause of cancer mortality worldwide and aerosol-mediated gene therapy endows numerous advantages compared to other traditional modalities. Here, we reported a folic acid (FA)-modified hyperbranched polyspermine (HPSPE) with prominent biocompatibility for lung cancer cell targeted gene therapy. FA was decorated to the HPSPE via an amidation reaction and the physicochemical properties of nanoplexes formed with DNA were characterized.

In vivo synergistic antitumor effect and safety of siRNA and lonidamine dual-loaded hierarchical targeted nanoparticles.

Based on development of nano-delivery system, co-delivery of chemotherapeutic drug and small interfering RNA (siRNA) has exerted a promising advantage in cancer therapy. In this work, the superiority of synergistic therapy and safety of the hierarchical targeted co-delivery system loaded with siRNA and lonidamine (LND) were evaluated. The in vivo tumor accumulation ability and cancer growth inhibition effect of the polymer-blend nanocarriers were evaluated by a H22 subcutaneous sarcoma model.

Polyamine metabolism-based dual functional gene delivery system to synergistically inhibit the proliferation of cancer.

Polyamine content, which is associated with tumor growth, can be regulated by ornithine decarboxylase (ODC) and S-adenosyl methionine decarboxylase (SAMDC), two key enzymes in polyamine biosynthesis. Here we aim to develop a pH-responsive cationic poly(agmatine) based on a polyamine analogue-agmatine that can dually function as a gene delivery vector as well as an anticancer agent by inhibiting ODC after intracellular degradation. The core-shell nanoparticles, formed by poly(agmatine)/SAMDC siRNA complex as a core, were coated with bovine serum albumin for better in vivo circulation stability and tumor targeting.

Biocompatible polymeric nanocomplexes as an intracellular stimuli-sensitive prodrug for type-2 diabetes combination therapy.

Combination therapy is usually considered as a promising strategy owing to its advantages such as reduced doses, minimized side effects and improved therapeutic efficiency in a variety of diseases including diabetes. Here we synthesized a new highly intracellular stimuli-sensitive chitosan-graft-metformin (CS-MET) prodrug by imine reaction between oxidative chitosan and metformin for type 2 diabetes (T2D) therapy. Hypothetically, CS-MET functions dually as an anti-diabetes prodrug as well as a gene delivery vector without superfluous materials.