The Combination of Sinusoidal Perfusion Enhancement and Apoptosis Inhibition by Riociguat Plus a Galactose-PEGylated Bilirubin Multiplexing Nanomedicine Ameliorates Liver Fibrosis Progression.

Chronic liver injury and continuous wound healing lead to extracellular matrix (ECM) deposition and liver fibrosis. The elevated production of reactive oxygen species (ROS) in the liver leads to the apoptosis of hepatocytes and the activation of hepatic stellate cells (HSCs). In the current study, we describe a combination strategy of sinusoidal perfusion enhancement and apoptosis inhibition enabled by riociguat together with a tailor-designed galactose-PEGylated bilirubin nanomedicine (Sel@GBRNPs). Riociguat enhanced sinusoidal perfusion and decreased the associated ROS accumulation and inflammatory state of the fibrotic liver. Concurrently, hepatocyte-targeting galactose-PEGylated bilirubin scavenged excessive ROS and released encapsulated selonsertib. The released selonsertib inhibited apoptosis signal-regulating kinase 1 (ASK1) phosphorylation to alleviate apoptosis in hepatocytes. The combined effects on ROS and hepatocyte apoptosis attenuated the stimulation of HSC activation and ECM deposition in a mouse model of liver fibrosis. This work provides a novel strategy for liver fibrosis treatment based on sinusoidal perfusion enhancement and apoptosis inhibition.

In Situ Transforming RNA Nanovaccines from Polyethylenimine Functionalized Graphene Oxide Hydrogel for Durable Cancer Immunotherapy.

Messenger RNA (mRNA) vaccine is a promising candidate in cancer immunotherapy as it can encode tumor-associated antigens with an excellent safety profile. Unfortunately, the inherent instability of RNA and translational efficiency are major limitations of RNA vaccine. Here, we report an injectable hydrogel formed with graphene oxide (GO) and polyethylenimine (PEI), which can generate mRNA (ovalbumin, a model antigen) and adjuvants (R848)-laden nanovaccines for at least 30 days after subcutaneous injection. The released nanovaccines can protect the mRNA from degradation and confer targeted delivering capacity to lymph nodes. The data show that this transformable hydrogel can significantly increase the number of antigen-specific CD8+ T cells and subsequently inhibit the tumor growth with only one treatment. Meanwhile, this hydrogel can generate an antigen specific antibody in the serum which in turn prevents the occurrence of metastasis. Collectively, these results demonstrate the potential of the PEI-functionalized GO transformable hydrogel for effective cancer immunotherapy.

Assessment of the Biological Effects of a Multifunctional Nano-Drug-Carrier and Its Encapsulated Drugs.

Polymer-nanoparticle-encapsulated doxorubicin (DOX) and paclitaxel (TAX) have the potential for novel therapeutic use against cancer in the clinic. However, the systemic biological effect of the nanoparticle material, namely, methoxypoly(ethylene glycol)-poly(lactide-co-glycolide) (mPEG-PLGA), and its encapsulated drugs have not been fully studied. We have applied NMR-based metabonomics methodology to characterize and analyze the systemic metabolic changes in mice after being exposed to mPEG-PLGA, mPEG-PLGA-encapsulated DOX and TAX (NP-D/T), and their free forms. The study revealed that mPEG-PLGA exposure only induces temporary and slight metabolic alternations and that there are detoxification effects of nanoparticle packed with D/T drugs on the heart when comparing with free-form D/T drugs. Both NP-D/T and their free forms induce a shift in energy metabolism, stimulate antioxidation pathways, and disturb the gut microbial activity of the host. However, mPEG-PLGA packaging can relieve the energy metabolism inhibition and decrease the activation of antioxidation pathways caused by D/T exposure. These findings provide a holistic insight into the biological effect of polymer nanoparticle and nanoparticle-encapsulated drugs. This study also furthers our understanding of the molecular mechanisms involved in the amelioration effects of mPEG-PLGA packaging on the toxicity of the incorporated drugs.

Hepcidin levels in hyperprolactinemic women monitored by nanopore thin film based assay: correlation with pregnancy-associated hormone prolactin.

Hepcidin is a central regulator in human iron metabolism. Although it is often regarded as a promising indicator of iron status, the lack of effective quantification method has impeded the comprehensive assessment of its physiological and clinical significance. Herein we applied a newly established, nanopore film enrichment based hepcidin assay to examine the correlation between hepcidin and prolactin, the hormone with an important role during pregnancy and lactation. Women with pathologically elevated prolactin secretion (hyperprolactinemia) were found to have lower serum hepcidin compared to those with normal prolactin levels, without showing significant difference in other hepcidin-regulating factors. Moreover, prolactin-reducing drug bromocriptine mesylate resulted in elevated expression of the hepcidin in hyperprolactinemia patients. These findings suggest a possible role of prolactin in regulation of hepcidin, and may render hepcidin a useful biomarker for progress monitoring and treatment of iron-related diseases under hyperprolactinemic conditions. FROM THE CLINICAL EDITOR: The level of hepcidin has been shown to reflect the underlying iron status of the patient. Nonentheless, there is an urgent need of reliable, fast and easy-to-do hepcidin assay in the clinical setting. In this paper, the authors described a further modification of their previously described nanopore silica film-based enrichment approach for quantification of hepcidin and found correlation between hepcidin and prolactin. This new knowledge may add to current understanding of iron homeostasis during pregnancy.

Nanopore film based enrichment and quantification of low abundance hepcidin from human bodily fluids.

Endogenous peptides that represent biological and pathological information of disease have attracted interest for diagnosis. However, the extraction of those low abundance peptides is still a challenge because of the complexity of human bodily fluids (HBF). Hepcidin, a peptide hormone, has been recognized as a biomarker for iron-related diseases. There is no rapid and reliable way to enrich them from HBF. Here we describe a peptide extraction approach based on nanoporous silica thin films to successfully detect hepcidin from HBF. Cooperative functions of nanopore to biomolecule, including capillary adsorption, size-exclusion and electrostatic interaction, were systematically investigated to immobilize the target peptide. To promote this new approach to clinical practices, we further applied it to successfully assay the hepcidin levels in HBF provided by healthy volunteers and patients suffering from inflammation. Our finding provides a high-throughput, rapid, label-free and cost-effective detection method for capturing and quantifying low abundance peptides from HBF. FROM THE CLINICAL EDITOR: Diagnosing diseases with low concentration peptide biomarkers remains challenging. This team of authors describes a peptide extraction approach based on nanoporous silica thin films to successfully detect low concentrations of hepcidin from human body fluids collected from 119 healthy volunteers and 19 inflammation patients.

Balancing mechanical property and swelling behavior of bacterial cellulose film by in-situ adding chitosan oligosaccharide and covalent crosslinking with γ-PGA.

Bacterial cellulose (BC) is an ideal candidate material for drug delivery, but the disbalance between the swelling behavior and mechanical properties limits its application. In this work, covalent crosslinking of γ-polyglutamic acid (γ-PGA) with the chitosan oligosaccharide (COS) embedded in BC was designed to remove the limitation. As a result, the dosage, time, and batch of COS addition significantly affected the mechanical properties and the yield of bacterial cellulose complex film (BCCF). The addition of 2.25 % COS at the incubation time of 0.5, 1.5, and 2 d increased the Young's modulus and the yield by 5.65 and 1.42 times, respectively, but decreased the swelling behavior to 1774 %, 46 % of that of native BC. Covalent γ-PGA transformed the dendritic structure of BCCF into a spider network, decreasing the porosity and increasing the swelling behavior by 3.46 times. The strategy balanced the swelling behavior and mechanical properties through tunning hydrogen bond, electrostatic interaction, and amido bond. The modified BCCF exhibited a desired behavior of benzalkonium chlorides transport, competent for drug delivery. Thereby, the strategy will be a competent candidate to modify BC for such potential applications as wound dressing, artificial skin, scar-inhibiting patch, and so on.

Nanocarriers based on bacterial membrane materials for cancer vaccine delivery.

Here we present a protocol for the construction and use of two types of nanocarrier based on bacterial membrane materials for cancer vaccine delivery. Cancer vaccines induce tumor regression through triggering the specific T-cell responses against tumor neoantigens, a process that can be enhanced by nanocarrier delivery. Inspired by the body's natural immune defenses against bacterial invasion, we have developed two different types of nanocarrier based on bacterial membrane materials, which employ genetically engineered outer-membrane vesicles (OMVs), or hybrid membrane vesicles containing bacterial cytoplasmic membrane, respectively. The OMV-based nanocarriers can rapidly display different tumor antigens through the surface modified Plug-and-Display system, suitable for customized cancer vaccines when the tumor neoantigens can be identified. The hybrid membrane-based nanocarriers are prepared through fusion of the bacterial cytoplasmic membrane and the primary tumor cell membrane from surgically removed tumor tissues, possessing unique advantages as personalized cancer vaccines when the neoantigens are not readily available. Compared with chemically synthesized nanocarriers such as liposomes and polymer without intrinsic adjuvant properties, owing to the large amounts of pathogen-associated molecular patterns, the two nanocarriers can activate the antigen-presenting cells while delivering multiple antigens, thus inducing effective antigen presentation and robust adaptive immune activation. Excluding bacterial culture and tumor tissue collection, the preparation of OMV- and hybrid membrane-based nanocarriers takes ~8 h and 10 h for tumor vaccine construction, respectively. We also detail how to use these nanocarriers to create cancer nanovaccines and evaluate their immunostimulatory and antitumor effects.

Specific Silencing of Microglial Gene Expression in the Rat Brain by Nanoparticle-Based Small Interfering RNA Delivery.

Microglia are the major innate immune cells in the brain and are essential for maintaining homeostasis in a neuronal microenvironment. Currently, a genetic tool to modify microglial gene expression in specific brain regions is not available. In this report, we introduce a tailor-designed method that uses lipid and polymer hybridized nanoparticles (LPNPs) for the local delivery of small interfering RNAs (siRNAs), allowing the silencing of specific microglial genes in the hypothalamus. Our physical characterization proved that this LPNP-siRNA was uniform and stable. We demonstrated that, due to their natural phagocytic behavior, microglial cells are the dominant cell type taking up these LPNPs in the hypothalamus of rats. We then tested the silencing efficiency of LPNPs carrying a cluster of differentiation molecule 11b (CD11b) or Toll-like receptor 4 (TLR4) siRNA using different in vivo and in vitro approaches. In cultured microglial cells treated with LPNP-CD11b siRNA or LPNP-TLR4 siRNA, we found a silencing efficiency at protein expression levels of 65 or 77%, respectively. In line with this finding, immunohistochemistry and western blotting results from in vivo experiments showed that LPNP-CD11b siRNA significantly inhibited microglial CD11b protein expression in the hypothalamus. Furthermore, following lipopolysaccharide (LPS) stimulation of cultured microglial cells, gene expression of the TLR4 downstream signaling component myeloid differentiation factor 88 and its associated cytokines was significantly inhibited in LPNP-TLR4 siRNA-treated microglial cells compared with cells treated with LPNP-scrambled siRNA. Finally, after LPNP-TLR4 siRNA injection into the rat hypothalamus, we observed a significant reduction in microglial activation in response to LPS compared with the control rats injected with LPNP-scrambled siRNA. Our results indicate that LPNP-siRNA is a promising tool to manipulate microglial activity locally in the brain and may serve as a prophylactic approach to prevent microglial dysfunction-associated diseases.

Rapid Surface Display of mRNA Antigens by Bacteria-Derived Outer Membrane Vesicles for a Personalized Tumor Vaccine.

Therapeutic mRNA vaccination is an attractive approach to trigger antitumor immunity. However, the mRNA delivery technology for customized tumor vaccine is still limited. In this work, bacteria-derived outer membrane vesicles (OMVs) are employed as an mRNA delivery platform by genetically engineering with surface decoration of RNA binding protein, L7Ae, and lysosomal escape protein, listeriolysin O (OMV-LL). OMV-LL can rapidly adsorb box C/D sequence-labelled mRNA antigens through L7Ae binding (OMV-LL-mRNA) and deliver them into dendritic cells (DCs), following by the cross-presentation via listeriolysin O-mediated endosomal escape. OMV-LL-mRNA significantly inhibits melanoma progression and elicits 37.5% complete regression in a colon cancer model. OMV-LL-mRNA induces a long-term immune memory and protects the mice from tumor challenge after 60 days. In summary, this platform provides a delivery technology distinct from lipid nanoparticles (LNPs) for personalized mRNA tumor vaccination, and with a "Plug-and-Display" strategy that enables its versatile application in mRNA vaccines.

Engineered Bacterial Outer Membrane Vesicles as Controllable Two-Way Adaptors to Activate Macrophage Phagocytosis for Improved Tumor Immunotherapy.

The most immune cells infiltrating tumor microenvironment (TME), tumor-associated macrophages (TAMs) closely resemble immunosuppressive M2-polarized macrophages. Moreover, tumor cells exhibit high expression of CD47 "don't eat me" signal, which obstructs macrophage phagocytosis. The precise and efficient activation of TAMs is a promising approach to tumor immunotherapy; however, re-education of macrophages remains a challenge. Bacteria-derived outer membrane vesicles (OMVs) are highly immunogenic nanovesicles that can robustly stimulate macrophages. Here, an OMV-based controllable two-way adaptor is reported, in which a CD47 nanobody (CD47nb) is fused onto OMV surface (OMV-CD47nb), with the outer surface coated with a polyethylene glycol (PEG) layer containing diselenide bonds (PEG/Se) to form PEG/Se@OMV-CD47nb. The PEG/Se layer modification not only mitigates the immunogenicity of OMV-CD47nb, thereby remarkedly increasing the dose that can be administered safely through intravenous injection, but also equips the formulation with radiation-triggered controlled release of OMV-CD47nb. Application of radiation to tumors in mice injected with the nanoformulation results in remodeling of TME. As two-way adaptors, OMV-CD47nb activates TAM phagocytosis of tumor cells via multiple pathways, including induction of M1 polarization and blockade of "don't eat me" signal. Moreover, this activation of TAMs results in the stimulation of T cell-mediated antitumor immunity through effective antigen presentation.

Responsive and activable nanomedicines for remodeling the tumor microenvironment.

Here we describe two protocols for the construction of responsive and activable nanomedicines that regulate the tumor microenvironment (TME). The TME is composed of all non-cellular and cellular components surrounding a tumor, including the surrounding blood vessels, immune cells, fibroblasts, signaling molecules, and extracellular matrix and has a crucial role in tumor initiation, growth, and metastasis. Owing to the relatively stable properties of the TME compared to tumor cells, which exhibit frequent genetic mutations and epigenetic changes, therapeutic strategies targeting the TME using multifunctional nanomedicines hold great potential for anti-tumor therapy. By regulating tumor-associated platelets and pancreatic stellate cells (PSCs), the two major players in the TME, we can effectively manipulate the physiological barriers for enhanced drug delivery and significantly improve the tumor penetration and therapeutic efficacy of chemotherapeutics. The preparation and characterization of the multifunctional nanoparticles takes ~10 h for tumor-associated platelet regulation and 16 h for PSC regulation. These nanoformulations can be readily applied to regulate other components in the TME to realize synergistic or additive anti-tumor activity.

Biomembrane-based nanostructures for cancer targeting and therapy: From synthetic liposomes to natural biomembranes and membrane-vesicles.

The translational success of liposomes in chemotherapeutics has already demonstrated the great potential of biomembrane-based nanostructure in effective drug delivery. Meanwhile, increasing efforts are being dedicated to the application of naturally derived lipid membranes, including cellular membranes and extracellular vesicles in anti-cancer therapies. While synthetic liposomes support superior multifunctional flexibility, natural biomembrane materials possess interesting biomimetic properties and can also be further engineered for intelligent design. Despite being remarkably different from each other in production and composition, the phospholipid bilayer structure in common allows liposomes, cell membrane-derived nanomaterials, and extracellular vesicles to be modified, functionalized, and exploited in many similar manners against challenges posed by tumor-targeted drug delivery. This review will summarize the recent advancements in engineering the membrane-derived nanostructures with "intelligent" modules to respond, regulate, and target tumor cells and the microenvironment to fight against malignancy. We will also discuss perspectives of combining engineered functionalities with naturally occurring activity for enhanced cancer therapy.

Fabrication of a porous chitosan/poly-(γ-glutamic acid) hydrogel with a high absorption capacity by electrostatic contacts.

A porous chitosan (CS)/poly-(γ-glutamic acid) (γ-PGA) hydrogel was prepared by polymerization by electrostatic contacts of CS with γ-PGA without linker. The porosity of the hydrogel remarkably depends on γ-PGA content, pH regulator, and drying way. The optimization of them had given the hydrogel a high swelling capacity of 1398%, 11-fold higher than that of neat CS hydrogel. The hydrogel was applied to recover bovine serum albumin (BSA) from aqueous solution, and its adsorption capacity was influenced by the initial concentration and pH of BSA solution. Based on the studies of kinetics and isotherm, a high equilibrium adsorption capacity (qe = 948 mg/g) and a correlation coefficient of 0.996 were calculated from pseudo-second order kinetic equation, and a high affinitive constant (kF = 472 mL/mg) and a high saturated absorption capacity (qm = 1818.5 mg/g) were observed from Freundlich isotherm equation, indicating the porous hydrogel will be a good absorbent for protein recovery from sewage.

Engineered Nanoplatelets for Targeted Delivery of Plasminogen Activators to Reverse Thrombus in Multiple Mouse Thrombosis Models.

Rapid cut-off of blood supply in diseases involving thrombosis is a major cause of morbidity and mortality worldwide. However, the current thrombolysis strategies offer limited results due to the therapeutics' short half-lives, low targeting ability, and unexpected bleeding complications. Inspired by the innate roles of platelets in hemostasis and pathological thrombus, platelet membrane-camouflaged polymeric nanoparticles (nanoplatelets) are developed for targeting delivery of the thrombolytic drug, recombinant tissue plasminogen activator (rt-PA), to local thrombus sites. The tailor-designed nanoplatelets efficiently accumulate at the thrombi in pulmonary embolism and mesenteric arterial thrombosis model mice, eliciting a significantly enhanced thrombolysis activity compared to free rt-PA. In addition, the nanoplatelets exhibit improved therapeutic efficacy over free rt-PA in an ischemic stroke model. Analysis of in vivo coagulation indicators suggests the nanoplatelets might possess a low risk of bleeding complications. The hybrid biomimetic nanoplatelets described offer a promising solution to improve the efficacy and reduce the bleeding risk of thrombolytic therapy in a broad spectrum of thrombosis diseases.

Sulforaphane Mediates Glutathione Depletion via Polymeric Nanoparticles to Restore Cisplatin Chemosensitivity.

Platinum (Pt)-based chemotherapy is a broadly used therapeutic regimen against various cancers. However, the insufficient cellular uptake, deactivation by thiol-containing species and nonspecific distribution of cisplatin (CDDP) result in its low chemosensitivity as well as systemic side effects, which can largely constrain the employment of CDDP in clinical treatment. To circumvent these problems, in this study, polymeric nanoparticles were utilized to codeliver a water-soluble CDDP derivative, poly(γ,l-glutamic acid)-CDDP conjugate, and a naturally occurring compound derived from broccoli, sulforaphane, which can achieve efficient glutathione (GSH) depletion, to improve the accumulation of CDDP in cancer cells. Results show that compared with combinational treatment of CDDP and SFN, the nanoparticles were more effectively internalized and could significantly reduce GSH content in breast cancer cells, leading to a notable increase in DNA-bound Pt and DNA damage-induced apoptosis. Moreover, in an orthotopic breast cancer model, the nanoparticles achieved a significantly higher tumor accumulation and exhibited a more powerful antitumor activity. Finally, this nanoenhanced chemotherapy was further confirmed in a liver cancer model with high-expression of GSH. Taken together, this sulforaphane-based nanostrategy holds great promise to enhance the sensitivity and therapeutic efficacy of Pt-based chemotherapy.

Synthesis and Imaging of Biocompatible Graphdiyne Quantum Dots.

Graphdiyne has attracted much interest from researchers for their potential applications in energy storage, catalysis, and biomedical areas. As one of the derivatives of graphdiyne, graphdiyne quantum dots (GDQDs) may possess superior bioactivity due to active acetylene units. However, the biological application of biocompatible GDQDs have not been reported so far. Herein, GDQDs with uniform size and good crystallization were prepared via a classical solvothermal method. The GDQDs exhibit excitation- and pH-dependent fluorescence emission as well as superior photostability, demonstrating their potential for bioimaging. The GDQDs demonstrate efficient cellular uptake and cell imaging without induction of detectable cytotoxic effects in vitro. Systematical safety evaluation further confirmed good biocompatibility of the GDQDs in vivo. Our study preliminarily validates the application of the GDQDs in biomedicine and encourages more thorough studies for better realizing the potential of GDQDs.

An Extendable Star-Like Nanoplatform for Functional and Anatomical Imaging-Guided Photothermal Oncotherapy.

Combining informative imaging methodologies with effective treatments to destroy tumors is of great importance for oncotherapy. Versatile nanotheranostic agents that inherently possess both diagnostic imaging and therapeutic capabilities are highly desirable to meet these requirements. Here, a simple but powerful nanoplatform based on polydopamine-coated gold nanostar (GNS@PDA), which can be easily diversified to achieve various function extensions, is designed to realize functional and anatomical imaging-guided photothermal oncotherapy. This nanoplatform intrinsically enables computed tomography/photoacoustic/two-photon luminescence/infrared thermal tetramodal imaging and can further incorporate fibroblast activation protein (FAP, a protease highly expressed in most of tumors) activatable near-infrared fluorescence imaging and Fe3+-based magnetic resonance imaging for comprehensive diagnosis. Moreover, GNS@PDA exhibits excellent photothermal performance and efficient tumor accumulation. Under the precise guidance of multimodal imaging, GNS@PDA conducts homogeneous photothermal ablation of bulky solid tumors (∼200 mm3) in a xenograft mouse model. These results suggest great promise of this extendable nanoplatform for cancer theranostics.

Co-Delivery of Gemcitabine and Mcl-1 SiRNA via Cationic Liposome-Based System Enhances the Efficacy of Chemotherapy in Pancreatic Cancer.

Myeloid cell leukemia 1 (Mcl-1) overexpression is found in various human tumors and has emerged as a promising new target for pancreatic cancer treatment. Recent research has found that most pancreatic cancers develop resistance to the current first-line chemotherapeutic drug, gemcitabine (Gem), and high expression of Mcl-1 can reduce the sensitivity of pancreatic cancer cells to Gem chemotherapy. Therefore, novel strategies, such as combination therapy, to overcome resistance of Gem chemotherapy are needed urgently. Here, we employed a lipid-based delivery system (LPs) to codeliver Mcl-1 siRNA and Gem for pancreatic cancer treatment, named LP-Gem-siMcl-1. LP-Gem-siMcl-1 exhibited an increased cellular uptake, enhanced Mcl-1 down-regulation efficacy, and significant cytotoxicity in the human pancreatic carcinoma cell lines PANC-1 and BxPC-3. Furthermore, tumor inhibition in vivo proved that LP-Gem-siMcl-1 has higher anti-tumor efficiency than LP-siMcl-1 plus LP-Gem, indicating the synergistic anti-tumor effects of Gem and siMcl-1. Meanwhile, histological analysis demonstrated that LPs could efficiently co-deliver Gem and Mcl-1 siRNA to cancerous cells and overcome the resistance of Gem. Taken together, our results offer proof that LP-Gem-siMcl-1 is an effective co-delivery system to treat pancreatic cancers and may serve as a valuable tool for developing new strategies for cancer therapy.

Engineering Biomimetic Platesomes for pH-Responsive Drug Delivery and Enhanced Antitumor Activity.

Biomimetic camouflage, i.e., using natural cell membranes for drug delivery, has demonstrated advantages over synthetic materials in both pharmacokinetics and biocompatibility, and so represents a promising solution for the development of safe nanomedicine. However, only limited efforts have been dedicated to engineering such camouflage to endow it with optimized or additional properties, in particular properties critical to a "smart" drug delivery system, such as stimuli-responsive drug release. A pH-responsive biomimetic "platesome" for specific drug delivery to tumors and tumor-triggered drug release is described. This platesome nanovehicle is constructed by merging platelet membranes with functionalized synthetic liposomes and exhibits enhanced tumor affinity, due to its platelet membrane-based camouflage, and selectively releases its cargo in response to the acidic microenvironment of lysosomal compartments. In mouse cancer models, it shows significantly better antitumor efficacy than nanoformulations based on a platesome without pH responsiveness or those based on traditional pH-sensitive liposomes. A convenient way to incorporate stimuli-responsive features into biomimetic nanoparticles is described, demonstrating the potential of engineered cell membranes as biomimetic camouflages for a new generation of biocompatible and efficient nanocarriers.

Sustained release of sodium deoxycholate from PLGA-PEG-PLGA thermosensitive polymer.

Delivery of the drugs to the target tissue and reducing their side effects on surrounding tissues is still a significant challenge for pharmaceutical scientists. The aim of this study was to investigate the suitability of PLGA-PEG-PLGA triblock copolymer as a matrix material for a sustained-release system of sodium deoxycholate (NaDC). The copolymer was synthesized by ring-opening polymerization reaction, using microwave irradiation and characterized by different techniques. It was shown that the introduction of NaDC to the PLGA-PEG-PLGA copolymer did not influence its inherent sol-gel transition behaviour, but increased the sol-gel transition. The results showed the appropriate NaDC/polymer interaction and the formation of NaDC/polymer-mixed micelle. The sustained release of NaDC from the copolymer lasted for 2 days. This release can be attributed to the formation of NaDC/polymer-mixed micelles and trapping NaDC in the copolymer matrix. The cytolytic efficacy of NaDC-loaded copolymer and sustained release of NaDC were investigated on human adipocytes. Overall a sustained-release formulation for NaDC can be used to study localized fat dissolution.