Decellularized extracellular matrix-based disease models for drug screening.

drug screening endeavors to replicate cellular states closely resembling those encountered , thereby maximizing the fidelity of drug effects and responses within the body. Decellularized extracellular matrix (dECM)-based materials offer a more authentic milieu for crafting disease models, faithfully emulating the extracellular components and structural complexities encountered by cells . This review discusses recent advancements in leveraging dECM-based materials as biomaterials for crafting cell models tailored for drug screening.

Targeting Inflammatory Lesions Facilitated by Galactosylation Modified Delivery System Eudragit/Gal-PLGA@Honokiol for the treatment of Ulcerative Colitis.

Honokiol (HNK) is one of the bioactive ingredients from the well-known Chinese herbal medicine Magnolia officinalis, and its research interests is rising for its extensive pharmacological activities, including novel therapeutic effect on ulcerative colitis (UC). However, further application of HNK is largely limited by its unique physicochemical properties, such as poor water solubility, low bioavailability, as well as unsatisfied targeting efficacy for inflammatory lesions. In this study, we constructed galactosylation modified PLGA nanoparticles delivery system for efficient target delivery of HNK to the colitic lesions, which could lay a research foundation for the deep development of HNK for the treatment of UC.

Enhanced Tumor Site Accumulation and Therapeutic Efficacy of Extracellular Matrix-Drug Conjugates Targeting Tumor Cells.

The extracellular matrix (ECM) engages in regulatory interactions with cell surface receptors through its constituent proteins and polysaccharides. Therefore, nano-sized extracellular matrix conjugated with doxorubicin (DOX) is utilized to produce extracellular matrix-drug conjugates (ECM-DOX) tailored for targeted delivery to cancer cells. The ECM-DOX nanoparticles exhibit rod-like morphology, boasting a commendable drug loading capacity of 4.

Destruction of vascular endothelial glycocalyx during formation of pre-metastatic niches.

A special microenvironment called the "pre-metastatic niche" is thought to help primary tumor cells migrate to new tissues and invade them, in part because the normal barrier function of the vascular endothelium is compromised. While the primary tumor itself can promote the creation of such niches by secreting pro-metastatic factors, the underlying molecular mechanisms are still poorly understood. Here, we show that the injection of primary tumor-secreted pro-metastatic factors from B16F10 melanoma or 4T1 breast cancer cells into healthy mice can induce the destruction of the vascular endothelial glycocalyx, which is a polysaccharide coating on the vascular endothelial lumen that normally inhibits tumor cell passage into and out of the circulation.

Constructing Tumor Organoid-like Tissue for Reliable Drug Screening Using Liver-Decellularized Extracellular Matrix Scaffolds.

The interplay between cells and their microenvironments plays a pivotal role in drug screening. Creating an environment that faithfully mimics the conditions of tumor cells within organ tissues is essential for enhancing the relevance of drug screening to real-world clinical scenarios. In our research, we utilized chemical decellularization techniques to engineer liver-decellularized extracellular matrix (L-dECM) scaffolds.

Co-delivery of microRNA-150 and quercetin by lipid nanoparticles (LNPs) for the targeted treatment of age-related macular degeneration (AMD).

Age-related macular degeneration (AMD) is characterized by choroidal neovascularization (CNV), which leads to severe vision loss in middle-aged and elderly patients. Current treatments for CNV show weak, transient efficacy, and they can cause several adverse effects. A potential new treatment is to use microRNA-150 (mR150), which regulates physiological and pathological angiogenesis by modulating the expression of CXCR4 at the post-transcriptional level.

Antibody-based drug delivery systems for cancer therapy: Mechanisms, challenges, and prospects.

In recent years, antibody-based cancer therapy has emerged as one of the efficient therapeutic strategies, such as immune checkpoint inhibitors (ICIs), angiogenesis inhibitors, antibody-drug conjugates (ADCs), multi-specific antibodies, and chimeric antigen receptor T (CAR-T) cells, among others. To date, various drug delivery platforms have been developed to improve the bioavailability, delivery convenience, and reduced toxicity towards increased therapeutic efficacy of antibodies. Herein, we emphasize the clinical manifestations of various antibody-based tumor therapies, highlighting their mechanisms and applications for cancer therapy.

Antibody and Cellular-Based Therapies for Pediatric Acute Lymphoblastic Leukemia: Mechanisms and Prospects.

Background: Acute lymphoblastic leukemia (ALL) is one of the most commonly diagnosed cancers in children. Despite enormous efforts to treat ALL over the past decade, the intensity of conventional chemotherapeutic strategies has reached the tolerance limit. Among various recently developed therapeutic approaches, antibody and cellular-based therapies showed less toxicity and better curative effect.

3D bioprinting of conductive hydrogel for enhanced myogenic differentiation.

Recently, hydrogels have gained enormous interest in three-dimensional (3D) bioprinting toward developing functional substitutes for tissue remolding. However, it is highly challenging to transmit electrical signals to cells due to the limited electrical conductivity of the bioprinted hydrogels. Herein, we demonstrate the 3D bioprinting-assisted fabrication of a conductive hydrogel scaffold based on poly-3,4-ethylene dioxythiophene (PEDOT) nanoparticles (NPs) deposited in gelatin methacryloyl (GelMA) for enhanced myogenic differentiation of mouse myoblasts (C2C12 cells).

Self-propelling micro-/nano-motors: Mechanisms, applications, and challenges in drug delivery.

In recent times, numerous efforts have been put forward to fabricating the self-propelling micro-/nano-motors (MNMs) for various applications, such as drug delivery, environmental remediation, biosensing, and precision surgery at the micro-/nanoscale, among others. Owing to their potential advantages, the application of such innovative architectures has been increasingly recognized towards addressing various challenges in the related fields. Specifically, these MNMs offer enormous potential in nanomedicine in overcoming the significant challenge of low permeation of the biological barriers.

Synergistic antitumor efficacy of doxorubicin and gambogic acid-encapsulated albumin nanocomposites.

Despite the success, the applicability of traditional chemotherapy still faces several challenges in treating cancer-related ailments, such as enormous toxicity and adverse effects. Combinatorial chemotherapy at reduced doses can offer augmented therapeutic efficiency through multiple mechanisms and even substantially circumvents the issues of toxicity and adverse effects. To demonstrate these facts, herein, two kinds of antitumor drugs, doxorubicin (DOX) and gambogic acid (GA), are encapsulated in bovine serum albumin (BSA) nanoparticles distinctly, resulting in DNP and GNP, respectively.

Synergistic antitumor efficacy of hybrid micelles with mitochondrial targeting and stimuli-responsive drug release behavior.

The term synergism means that the overall therapeutic benefits should be greater than the sum of the effects of individual agents and that the optimal therapeutic efficacy can be achieved at reduced doses. Micellar systems usually fail to deliver multiple drugs to target sites at synergistic doses and thus are not able to maximize the antitumor efficacy. In the current study, we demonstrate a strategy to coordinate the release of camptothecin (CPT) and α-tocopheryl succinate (TOS) from hybrid micelles for nucleus and mitochondrion interferences.

Uniform field electrospinning for 3D printing of fibrous configurations as strain sensors.

Electrospinning is becoming an efficient method to produce fibers in the submicron range, but the bending instability of conventional electrospinning system (CES) brings limitations in the distinctive deposition of electrospun fibers. Herein, we proposed a strategy to update the electrospinning system through establishment of a uniform electric field, realizing 3D printing of electrospun fibers with well-controlled, low-cost, and template-free manners. The uniform field electrospinning (UFES) apparatus is configured by inserting the electrospinning nozzle into the center of an aided metal plate.

Sequential Drug Release to Modulate Collagen Synthesis and Promote Micelle Penetration in Tumors.

Cancer chemotherapy is confronted with insufficient drug penetration in tumors. "Solid tumor priming" is proposed to modulate the abnormal tumor microenvironment but suffers from limited digestion efficiency and underlying tumor metastasis. Losartan (Los) and telmisartan (Tel) are well-known antihypertensive agents and show capabilities in inhibiting collagen synthesis by cancer-associated fibroblasts.

Bacterial microbots for acid-labile release of hybrid micelles to promote the synergistic antitumor efficacy.

Unlabelled: Bacteria have inherent properties of self-propelled navigation and specific infiltration into solid tumors. In the current study, we investigate a novel type of bacterial microbots for delivery of hybrid micelles to promote the synergistic antitumor efficacy. Escherichia coli Nissle 1917 (EcN) is used as a bacterial carrier to immobilize amphiphilic copolymers through acid-labile 2-propionic-3-methylmaleic anhydride (CDM) linkers.

Acid-Labile Degradation of Injectable Fiber Fragments to Release Bioreducible Micelles for Targeted Cancer Therapy.

Cancer chemotherapy is confronted with difficulties enhancing the tumor accumulation, improving the bioavailability, and relieving the adverse effect of chemotherapeutic agents. To address the challenges, this study proposes a feasible strategy to realize a sustained release of drug-loaded micelles from fiber fragments after intratumoral injection. Camptothecin (CPT) is grafted on hyaluronic acid (HA) via 3,3'-dithiodipropionic acid to obtain reduction-sensitive promicelle polymers (PM), which are conjugated with poly(d,l-lactide) via 2-propionic-3-methylmaleic anhydride (CDM) to obtain acid-labile copolymers for the preparation of injectable fiber fragments.

An implantable depot capable of in situ generation of micelles to achieve controlled and targeted tumor chemotherapy.

Unlabelled: Camptothecin (CPT)-containing promicelle polymers (PM) based on 4-armed poly(ethylene glycol) (PEG) were developed previously to self-assemble into folate-targeted and glutathione (GSH)-sensitive micelles (M). To address severe systemic toxicity and lack of tumor specificity implicated in the intravenous administration of M, a micelle-generating depot has been developed by blend electrospinning of PEG-poly(lactide) (PELA) copolymers, PM and polyethylene oxide (PEO). Upon implantation of the depot onto a tumor, PM are sustainably released to self-assemble into M on the tumor site.

Tumor pH-Responsive Release of Drug-Conjugated Micelles from Fiber Fragments for Intratumoral Chemotherapy.

The tumor accumulation of micelles is essential to enhance the cellular uptake and extend the release of chemotherapeutic agents. In the previous study camptothecin (CPT)-conjugated micelles (M) were constructed with disulfide linkages and folate moieties for reduction-sensitive release and cell-selective uptake. This study proposes a strategy to integrate the promicelle polymers (PM) into fiber fragments for intratumoral injection, realizing acid-liable release of PM in response to acidic tumor microenvironment and spontaneous self-assembly into M.

Fluorescent Strips of Electrospun Fibers for Ratiometric Sensing of Serum Heparin and Urine Trypsin.

"Turn-on" or "turn-off" probes remain challenges in the establishment of sensitive, easily operated, and reliable methods for in situ monitoring bioactive substances. In the current study, electrospun fibrous strips are designed to provide straightforward observations of ratiometric color changes with the naked eye in the presence of serum heparin or urine trypsin. A tetraphenylethene (TPE) derivative is constructed and along with phloxine B is grafted on fibers, followed by protamine adsorption to induce static quenching of phloxine B and aggregation-induced emission of the TPE derivative.

Synergistic antitumor efficacy of redox and pH dually responsive micelleplexes for co-delivery of camptothecin and genes.

Unlabelled: Challenges remain to load and deliver two or multiple drugs of complementary effects for synergistic cancer therapies. In the current study, multiarmed amphiphilic copolymers of 4-arm poly(ethylene glycol) (PEG) and polyaspartate (PAsp) are created for conjugation of camptothecin (CPT) and condensation with tumor necrosis factor-α (TNF) plasmids. Diethylenetriamine (DET) is grafted on PAsp, and CPT is conjugated onto PAsp(DET) by disulfide linkages to form hydrophobic cores of micelles, followed by condensation with TNF plasmids to form micelleplexes.

Tunable conjugation densities of camptothecin on hyaluronic acid for tumor targeting and reduction-triggered release.

Unlabelled: Micelles self-assembled from drug-conjugated polymers indicate advantages in alleviating the premature release before reaching the intended site. Hyaluronic acid (HA) is known to specifically bind with a transmembrane glycoprotein CD44, overexpressed in many types of cancerous cells, and can also be served as micelle carriers. However, an excess amount of drug conjugation to HA backbone may be detrimental to the receptor-mediated cellular uptake.

Pharmacokinetics and antitumor efficacy of micelles assembled from multiarmed amphiphilic copolymers with drug conjugates in comparison with drug-encapsulated micelles.

The premature drug release and structural dissociation before reaching pathological sites have posed major challenges for self-assembled micelles. To address these challenges, star-shaped amphiphilic copolymers derived from 4-armed poly(ethylene glycol) (PEG) were proposed for chemical conjugation of chemotherapeutic drugs and assembly into drug-conjugated micelles (DCM) with reductive sensitivity. The current study aimed to elucidate the in vitro and in vivo performance of DCM and a comparison with conventional drug-encapsulated micelles (DEM) was initially launched.

Folate-decorated and reduction-sensitive micelles assembled from amphiphilic polymer-camptothecin conjugates for intracellular drug delivery.

It is one of the challenges for a wide clinical application of polymer micelles to address the structure disintegration and premature drug release before reaching a pathological site. In the current study, folic acid (FA)-decorated polymer-drug conjugates (FSC) were synthesized with disulfide linkages between camptothecin (CPT) and amphiphilic poly(ethylene glycol)-b-poly(ε-caprolactone) (PECL) copolymers. FSC conjugates were proposed to assemble into micelles with a hydrophobic core of PCL segments and CPT and a hydrophilic corona of PEG segments.

Multimeric immobilization of alcohol oxidase on electrospun fibers for valid tests of alcoholic saliva.

An accurate quantitation of ethanol is of great importance in clinical and forensic analyses. In the current study, alcohol oxidase (AOX) from Pichia pastoris, a multimeric enzyme consisting of eight identical subunits, was immobilized on electrospun polystyrene-co-maleic anhydride (PSMA) fibers for valid tests of alcoholic saliva. Branched polyethyleneimine (PEI) was grafted on PSMA fibers with a density of 0.