Disease-specific corona mediated co-delivery of MTX and siRNA-TNFα by a polypeptide nanoplatform with antigen-scavenging functions in psoriasis.

Psoriatic self-antigen LL37 has the ability to stimulate skin-homing T lymphocytes, which is the constitutive factor for the relapse of psoriasis. The local inflammatory modulation in psoriatic skin is not sufficient for the restoration of immune homeostasis. In this study, we found the expression levels of disease specific proteins including LL37, S100A8 and S100A9 were significantly increased in psoriasis.

Anti-CLL1 liposome loaded with miR-497-5p and venetoclax as a novel therapeutic strategy in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a lethal hematologic malignancy. Chemotherapy resistance results in a dismal survival rate of 1-2 years in older adults with AML. Therefore, novel therapies are urgently required.

Emulsifying properties of cellulose nanocrystals with different structures and morphologies from various solanaceous vegetable residues.

The stems of solanaceous vegetables with attractive source of cellulose, have caused severe environmental problems as agricultural residues. For the reutilization of the residues, this study isolated cellulose nanocrystals (CNs) from the stems of tomato, eggplant, and pepper to explore their applications in Pickering emulsions. Detailed analyses of the crystalline structure and morphology revealed differences in their emulsifying properties.

Lipid nanoparticle-mediated hepatocyte delivery of siRNA and silibinin in metabolic dysfunction-associated steatotic liver disease.

Lipid nanoparticle-mediated co-delivery of siRNA and small molecule holds a great potential to treat metabolic dysfunction-associated steatotic liver disease (MASLD). However, targeted delivery of therapeutics to hepatocytes remains challenging. Taking the advantage of rising low density lipoprotein receptor/very-low density lipoprotein receptor (LDLR/VLDR) levels in MASLD, the biological fate of dinonylamine-ethylene glycol chlorophosphate-1-nonanol (DNNA-COP-NA) based lipid nanoparticles (LNPs) was oriented to liver tissues via apolipoprotein E (ApoE)-LDLR/VLDLR pathway.

Bioresponsive nanocomplex integrating cancer-associated fibroblast deactivation and immunogenic chemotherapy for rebuilding immune-excluded tumors.

Cancer-associated fibroblasts (CAFs) play a crucial role in creating an immunosuppressive environment and remodeling the extracellular matrix within tumors, leading to chemotherapy resistance and limited immune cell infiltration. To address these challenges, integrating CAFs deactivation into immunogenic chemotherapy may represent a promising approach to the reversal of immune-excluded tumor. We developed a tumor-targeted nanomedicine called the glutathione-responsive nanocomplex (GNC).

Recent Progress in Nucleic Acid Pulmonary Delivery toward Overcoming Physiological Barriers and Improving Transfection Efficiency.

Pulmonary delivery of therapeutic agents has been considered the desirable administration route for local lung disease treatment. As the latest generation of therapeutic agents, nucleic acid has been gradually developed as gene therapy for local diseases such as asthma, chronic obstructive pulmonary diseases, and lung fibrosis. The features of nucleic acid, specific physiological structure, and pathophysiological barriers of the respiratory tract have strongly affected the delivery efficiency and pulmonary bioavailability of nucleic acid, directly related to the treatment outcomes.

Medulloblastoma targeted therapy: From signaling pathways heterogeneity and current treatment dilemma to the recent advances in development of therapeutic strategies.

Medulloblastoma (MB) is a major pediatric malignant brain tumor that arises in the cerebellum. MB tumors exhibit highly heterogeneous driven by diverse genetic alterations and could be divided into four major subgroups based on their different biological drivers and molecular features (Wnt, Sonic hedgehog (Shh), group 3, and group 4 MB). Even though the therapeutic strategies for each MB subtype integrate their pathogenesis and were developed to focus on their specific target sites, the unexpected drug non-selective cytotoxicity, low drug accumulation in the brain, and complexed MB tumor microenvironment still be huge obstacles to achieving satisfied MB therapeutic efficiency.

ROS-scavenging nanomedicine for "multiple crosstalk" modulation in non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a chronic inflammatory disease characterized by "multiple crosstalk" paths of insulin resistance, lipid metabolism, oxidative stress, . The combination of LY294002 and oridonin was proposed as a promising therapy by targeting insulin-PI3K/AKT signaling and NF-κB inflammatory pathway. However, due to oxidative stress, disease-associated upregulation of murine CYP3A11 activity can contribute to unexpected drug metabolism and disposition, which could seriously hinder the efficacy of LY294002 and oridonin.

Self-assembled thioether-bridged paclitaxel-dihydroartemisinin prodrug for amplified antitumor efficacy-based cancer ferroptotic-chemotherapy.

Ferroptosis has been proposed as one form of iron-dependent cell death, overgeneration of high-toxicity hydroxyl radicals (˙OH) tumor sites Fenton reactions induced cell membrane damage. However, the insufficient intracellular concentrations of both iron and HO limited the anticancer performance of ferroptosis. In this study, ROS-sensitive prodrug nanoassemblies composed of a PEG2000-ferrous compound and a single thioether bond bridged dihydroartemisinin-paclitaxel prodrug were constructed, which fully tapped ex/endogenous iron, ferroptosis inducers, and chemotherapeutic agents.

Anti-miR-96 and Hh pathway inhibitor MDB5 synergistically ameliorate alcohol-associated liver injury in mice.

Alcohol-associated liver disease (ALD) and its complications are significant health problems worldwide. Several pathways in ALD are influenced by alcohol that drives inflammation, fatty acid metabolism, and fibrosis. Although miR-96 has become a key regulator in several liver diseases, its function in ALD remains unclear.

Topical Delivery of ROS-Responsive Methotrexate Prodrug Nanoassemblies by a Dissolvable Microneedle Patch for Psoriasis Therapy.

Purpose: Oxidative stress, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and adenosine signaling are factors associated with psoriatic inflammation. Topical delivery of methotrexate (MTX) has become an option to overcome the side effects caused by systemic therapy in psoriasis, leading to the suppression of NF-κB activation through boosting adenosine release. However, thickened psoriatic skin is the primary restriction against local drug delivery.

CXCL10-coronated thermosensitive "stealth" liposomes for sequential chemoimmunotherapy in melanoma.

The interplay of liposome-protein corona hinders the clinical application of liposomes due to active macrophage sequestration and rapid plasma clearance. Here we showed that, CXCL10 as a therapeutic protein was coronated the thermosensitive liposomes to form stealth-like nanocarriers (CXCL10/TSLs). Decoration of the corona layer of CXCL10/TSLs by hyaluronic acid conjugated oridonin (ORD/CXCL10/TSLs), overcame the "fluid barrier" built by biological proteins, drastically reduced capture by leukocytes in whole blood, allowed the specific targeting of tumor sites.

Dual Targeting of Cancer Cells and MMPs with Self-Assembly Hybrid Nanoparticles for Combination Therapy in Combating Cancer.

The co-delivery of chemotherapeutic agents and immune modulators to their targets remains to be a great challenge for nanocarriers. Here, we developed a hybrid thermosensitive nanoparticle (TMNP) which could co-deliver paclitaxel-loaded transferrin (PTX@TF) and marimastat-loaded thermosensitive liposomes (MMST/LTSLs) for the dual targeting of cancer cells and the microenvironment. TMNPs could rapidly release the two payloads triggered by the hyperthermia treatment at the site of tumor.

Resolving hepatic fibrosis suppressing oxidative stress and an inflammatory response using a novel hyaluronic acid modified nanocomplex.

Hepatic fibrosis remains a serious threat to human health globally and there are no effective antifibrotic pharmacotherapeutic strategies, to date. Upon the activation of hepatic stellate cells, excess deposition of the extracellular matrix occurs, acting as a trigger that generates reactive oxygen species and an inflammatory response, thereby exacerbating the development of hepatic fibrosis and inflammation. In this study, we incorporated an idea that targets key pathways for developing novel anti-fibrosis nanomedicine.

Therapeutic targets, novel drugs, and delivery systems for diabetes associated NAFLD and liver fibrosis.

Type 2 diabetes mellitus (T2DM) associated non-alcoholic fatty liver disease (NAFLD) is the fourth-leading cause of death. Hyperglycemia induces various complications, including nephropathy, cirrhosis and eventually hepatocellular carcinoma (HCC). There are several etiological factors leading to liver disease development, which involve insulin resistance and oxidative stress.

Redox-responsive nanoplatform for codelivery of miR-519c and gemcitabine for pancreatic cancer therapy.

Desmoplastic and hypoxic pancreatic cancer microenvironment induces aberrant expression of miRNAs and hypoxia-inducible factor-1α (HIF-1α) responsible for gemcitabine (GEM) resistance. We demonstrated that miR-519c was down-regulated in pancreatic cancer and transfection of miR-519c in GEM-resistant pancreatic cancer cells inhibited HIF-1α level under hypoxia. We synthesized redox-sensitive mPEG--P(Asp)--DC--S-S-GEM polymer, with GEM payload of 14% (w/w) and 90% GEM release upon incubation with l-glutathione.

Drug Nanorod-Mediated Intracellular Delivery of microRNA-101 for Self-sensitization via Autophagy Inhibition.

Autophagy is closely related to the drug resistance and metastasis in cancer therapy. Nanoparticle-mediated co-delivery of combinatorial therapy with small-molecular drugs and nucleic acids is promising to address drug resistance. Here, a drug-delivering-drug (DDD) platform consisting of anti-tumor-drug nanorods as a vehicle for cytosol delivery of nucleic acid (miR-101) with potent autophagic-inhibition activity is reported for combinatorial therapy.

ROS-Responsive Polymeric Micelles for Triggered Simultaneous Delivery of PLK1 Inhibitor/miR-34a and Effective Synergistic Therapy in Pancreatic Cancer.

Ineffective drug delivery and poor prognosis are two major challenges in the treatment of pancreatic ductal adenocarcinoma (PDAC). While there is significant downregulation of tumor suppressor microRNA-34a (miR-34a), which targets many oncogenes related to proliferation, apoptosis, and invasion, high expression level of Polo-like kinase 1 (PLK1) is closely associated with short survival rates of pancreatic cancer patients. Therefore, the objective is to codeliver miR-34a mimic and small molecule PLK1 inhibitor volasertib (BI6727) using poly(ethylene glycol)-poly[aspartamidoethyl( p-boronobenzyl)diethylammonium bromide] (PEG-B-PAEBEA).

Drug-delivering-drug platform-mediated potent protein therapeutics a non-endo-lysosomal route.

Protein therapeutics is playing an increasingly critical role in treatment of human diseases. However, current vectors are captured by the digestive endo-lysosomal system, which results in an extremely low fraction (<2%) of protein being released in the cytoplasm. This paper reports a drug-delivering-drug platform (HA-PNPplex, 200 nm) for potent intracellular delivery of protein and combined treatment of cancer.

Amorphous Nanosuspensions Aggregated from Paclitaxel⁻Hemoglobulin Complexes with Enhanced Cytotoxicity.

Amorphous nanosuspensions (ANSs) enable rapid release and improved delivery of a poorly water-soluble drug; however, their preparation is challenging. Here, using hemoglobin (Hb) as a carrier, ANSs aggregated from paclitaxel (PTX)⁻Hb complexes were prepared to improve delivery of the hydrophobic anti-cancer agent. An affinity study demonstrated strong interaction between Hb and PTX.

Nanoplatform Assembled from a CD44-Targeted Prodrug and Smart Liposomes for Dual Targeting of Tumor Microenvironment and Cancer Cells.

The tumor microenvironment (TME) plays a critical role in tumor initiation, progression, invasion, and metastasis. Therefore, a therapy that combines chemotherapeutic drugs with a TME modulator could be a promising route for cancer treatment. This paper reports a nanoplatform self-assembled from a hyaluronic acid (HA)-paclitaxel (PTX) (HA-PTX) prodrug and marimastat (MATT)-loaded thermosensitive liposomes (LTSLs) (MATT-LTSLs) for the dual targeting of the TME and cancer cells.

Rod-Shaped Active Drug Particles Enable Efficient and Safe Gene Delivery.

Efficient microRNAs (miRNA) delivery into cells is a promising strategy for disease therapy, but is a major challenge because the available conventional nonviral vectors have significant drawbacks. In particular, after these vectors are entrapped in lysosomes, the escape efficiency of genes from lysosomes into the cytosol is less than 2%. Here, a novel approach for lethal-7a (let-7a) replacement therapy using rod-shaped active pure drug nanoparticles (≈130 nm in length, PNPs) with a dramatically high drug-loading of ≈300% as vectors is reported.

Cytosolic co-delivery of miRNA-34a and docetaxel with core-shell nanocarriers via caveolae-mediated pathway for the treatment of metastatic breast cancer.

Co-delivery of microRNAs and chemotherapeutic drugs into tumor cells is an attractive strategy for synergetic breast cancer therapy due to their complementary mechanisms. In this work, a core-shell nanocarrier coated by cationic albumin was developed to simultaneously deliver miRNA-34a and docetaxel (DTX) into breast cancer cells for improved therapeutic effect. The co-delivery nanocarriers showed a spherical morphology with an average particle size of 183.

Simultaneous determination of tazarotene and its active metabolite tazarotenic acid in minipig plasma by LC-MS/MS and its application in pharmacokinetic study after topical administration of tazarotene gel.

To study the systemic exposure of tazarotene formulation after topical administration, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of tazarotene and tazarotenic acid in minipig plasma. Similar extraction recoveries for both analytes were obtained after the plasma samples were acidified by glacial acetic acid (5%) and extracted by ethyl ether-cyclohexane (4:1, v/v). Separation of the analytes was achieved within a short time by the addition of 0.