NIR irradiation-controlled drug release utilizing injectable hydrogels containing gold-labeled liposomes for the treatment of melanoma cancer.

Drug-based chemotherapy is associated with serious side effects. We developed a chemotherapeutic system comprising a chitosan hydrogel (CH-HG) containing gold cluster-labeled liposomal doxorubicin (DOX) (CH-HG-GL) as an injectable drug depot system. CH-HG-GL can be directly injected into tumor tissue without a surgical procedure, allowing this system to act as a reservoir for liposomal DOX.

Efficacy of Combination Therapy with Linalool and Doxorubicin Encapsulated by Liposomes as a Two-in-One Hybrid Carrier System for Epithelial Ovarian Carcinoma.

Background: Epithelial ovarian cancer (EOC) is a fatal gynecologic malignancy that is usually treated with chemotherapy after surgery. However, patients who receive chemotherapy experience severe side effects because of the inherent toxicity and high dose of chemotherapeutics. To overcome these issues, we suggest a combination therapeutic strategy using liposomes encapsulating linalool nanoemulsions (LN-NEs) and doxorubicin (DOX), a chemotherapeutic drug, to increase their synergistic antitumor efficacy and reduce the incidence of side effects from chemotherapeutics for EOC.

Enhanced Antitumor Immunity Using a Tumor Cell Lysate-Encapsulated CO-Generating Liposomal Carrier System and Photothermal Irradiation.

Dendritic cell (DC)-based cancer immunotherapies have been studied extensively. In cancer immunotherapy, the initial key step is the delivery of tumor-specific antigens, leading to the maturation and activation of DCs. To promote effective antigen delivery, liposome-based delivery systems for tumor-specific antigens have been investigated, and although promising, a triggered release of the antigen from the liposome is required to attain an optimum immune response.

CD44-Targeting PLGA Nanoparticles Incorporating Paclitaxel and FAK siRNA Overcome Chemoresistance in Epithelial Ovarian Cancer.

Chemotherapy is commonly used in the treatment of ovarian cancer, yet most ovarian cancers harbor inherent resistance or develop acquired resistance. Therefore, novel therapeutic approaches to overcome chemoresistance are required. In this study, we developed a hyaluronic acid-labeled poly(d,l-lactide-co-glycolide) nanoparticle (HA-PLGA-NP) encapsulating both paclitaxel (PTX) and focal adhesion kinase (FAK) siRNA as a selective delivery system against chemoresistant ovarian cancer.

Selective delivery of PLXDC1 small interfering RNA to endothelial cells for anti-angiogenesis tumor therapy using CD44-targeted chitosan nanoparticles for epithelial ovarian cancer.

Angiogenesis plays an essential role in the growth and metastasis of tumor cells, and the modulation of angiogenesis can be an effective approach for cancer therapy. We focused on silencing the angiogenic gene PLXDC1 as an important factor for anti-angiogenesis tumor therapy. Herein, we developed PLXDC1 small interfering siRNA (siRNA)-incorporated chitosan nanoparticle (CH-NP/siRNA) coated with hyaluronic acid (HA) to target the CD44 receptor on tumor endothelial cells.

Pitch-tunable pillar arrays for high-throughput culture and immunohistological analysis of tumor spheroids.

Tumor spheroids are multicellular, three-dimensional (3D) cell culture models closely mimicking the microenvironments of human tumors , thereby providing enhanced predictability, clinical relevancy of drug efficacy and the mechanism of action. Conventional confocal microscopic imaging remains inappropriate for immunohistological analysis due to current technical limits in immunostaining using antibodies and imaging cells grown in 3D multicellular contexts. Preparation of microsections of these spheroids represents a best alternative, yet their sub-millimeter size and fragility make it less practical for high-throughput screening.

Antifibrotic effects of pentoxifylline improve the efficacy of gemcitabine in human pancreatic tumor xenografts.

We investigated the combinatorial effects of pentoxifylline (PTX) on the efficacy of gemcitabine (GEM) in a human pancreatic tumor xenograft model. PTX significantly improved the efficacy of GEM, as shown by a 50% reduction in tumor growth rate at 4 weeks of treatment compared with that in animals given GEM alone. The fluorescent drug doxorubicin (DOX) was used to test whether drug delivery was improved by PTX, contributing to the improved efficacy of GEM.

In vivo stepwise immunomodulation using chitosan nanoparticles as a platform nanotechnology for cancer immunotherapy.

Dentritic cell (DC)-based cancer immunotherapy faces challenges in both efficacy and practicality. However, DC-based vaccination requires multiple injections and elaborates ex vivo manipulation, which substantially limits their use. Therefore, we sought to develop a chitosan nanoparticle (CH-NP)-based platform for the next generation of vaccines to bypass the ex vivo manipulation and induce immune responses via active delivery of polyinosinic-polycytidylic acid sodium salt (poly I:C) to target Toll-like receptor 3 (TLR3) in endosomes.

Toll-like receptor 3-induced immune response by poly(d,l-lactide-co-glycolide) nanoparticles for dendritic cell-based cancer immunotherapy.

Dendritic cells (DCs) are potent professional antigen-presenting cells that are capable of initiating a primary immune response and activating T cells, and they play a pivotal role in the immune responses of the host to cancer. Prior to antigen presentation, efficient antigen and adjuvant uptake by DCs is necessary to induce their maturation and cytokine generation. Nanoparticles (NPs) are capable of intracellular delivery of both antigen and adjuvant to DCs.

Linalool-Incorporated Nanoparticles as a Novel Anticancer Agent for Epithelial Ovarian Carcinoma.

Although cytotoxic chemotherapy is widely used against epithelial ovarian cancer (EOC), adverse side effects and emergence of resistance can limit its utility. Therefore, new drugs with systemic delivery platforms are urgently needed for this disease. In this study, we developed linalool-incorporated nanoparticles (LIN-NP) as a novel anticancer agent.

Marbofloxacin-encapsulated microparticles provide sustained drug release for treatment of veterinary diseases.

Fluoroquinolone antibiotics with concentration-dependent killing effects and a well-established broad spectrum of activity are used commonly to treat infectious diseases caused by bacteria. However, frequent and excessive administration of these antibiotics is a serious problem, and leads to increased number of drug-resistant bacteria. Thus, there is an urgent need for novel fluoroquinolone antibiotic formulations that minimize the risk of resistance while maximizing their efficacy.

Gold cluster-labeled thermosensitive liposmes enhance triggered drug release in the tumor microenvironment by a photothermal effect.

Stimulus-triggered drug release based on the liposomal drug delivery platform has been studied vigorously to increase drug release at the target site. Although the delivery system has been developed, an effective carrier system is needed to achieve effective therapeutic efficacy. Therefore, we focused on the development of gold cluster bound thermosensitive liposomes (G-TSL), which are capable of triggered drug release when stimulated by external near-infrared (NIR) irradiation in the tumor microenvironment.

Therapeutic efficacy of doxorubicin delivery by a CO2 generating liposomal platform in breast carcinoma.

Unlabelled: Drug delivery using thermosensitive liposomes (TSL) has significant potential for tumor drug targeting and can be combined with local hyperthermia to trigger drug release. Although TSL-mediated drug delivery can be effective by itself, we developed doxorubicin (DOX)-containing CO2 bubble-generating TSL (TSL-C) that were found to enhance the antitumor effects of DOX owing to the synergism between burst release of drug and hyperthermia-induced CO2 generation. An ultrasound imaging system was used to monitor hyperthermia-induced CO2 generation in TSL-C and the results revealed that hyperthermia-induced CO2 generation in TSL-C led to increased DOX release compared to that observed for non-CO2-generating TSL.

GM-CSF-loaded chitosan hydrogel as an immunoadjuvant enhances antigen-specific immune responses with reduced toxicity.

Background: The application of vaccine adjuvants has been vigorously studied for a diverse range of diseases in order to improve immune responses and reduce toxicity. However, most adjuvants have limited uses in clinical practice due to their toxicity.

Methods: Therefore, to reduce health risks associated with the use of such adjuvants, we developed an advanced non-toxic adjuvant utilizing biodegradable chitosan hydrogel (CH-HG) containing ovalbumin (OVA) and granulocyte-macrophage colony-stimulating factor (GM-CSF) as a local antigen delivery system.

Enhanced localization of anticancer drug in tumor tissue using polyethylenimine-conjugated cationic liposomes.

Liposome-based drug delivery systems hold great potential for cancer therapy. However, to enhance the localization of payloads, an efficient method of systemic delivery of liposomes to tumor tissues is required. In this study, we developed cationic liposomes composed of polyethylenimine (PEI)-conjugated distearoylglycerophosphoethanolamine (DSPE) as an enhanced local drug delivery system.

Preparation and evaluation of poly(2-hydroxyethyl aspartamide)-hexadecylamine-iron oxide for MR imaging of lymph nodes.

The purpose of this study was to synthesize biocompatible poly(2-hydroxyethyl aspartamide)-C16-iron oxide (PHEA-C16-iron oxide) nanoparticles and to evaluate their efficacy as a contrast agent for magnetic resonance imaging of lymph nodes. The PHEA-C16-iron oxide nanoparticles were synthesized by coprecipitation method. The core size of the PHEA-C16-iron oxide nanoparticles was about 5 to 7 nm, and the overall size of the nanoparticles was around 20, 60, and 150 nm in aqueous solution.

Gd(III)-DOTA-modified sonosensitive liposomes for ultrasound-triggered release and MR imaging.

Ultrasound-sensitive (sonosensitive) liposomes for tumor targeting have been studied in order to increase the antitumor efficacy of drugs and decrease the associated severe side effects. Liposomal contrast agents having Gd(III) are known as a nano-contrast agent system for the efficient and selective delivery of contrast agents into pathological sites. The objective of this study was to prepare Gd(III)-DOTA-modified sonosensitive liposomes (GdSL), which could deliver a model drug, doxorubicin (DOX), to a specific site and, at the same time, be capable of magnetic resonance (MR) imaging.

Elastin-like polypeptide modified liposomes for enhancing cellular uptake into tumor cells.

Polyethylene glycol-modified (PEGylated) liposomes have been widely used because of their long circulation time, but they have a major drawback of limited cellular uptake. In this study, liposomes modified with a thermosensitive biopolymer, elastin-like polypeptide (ELP), were prepared to enhance cellular uptake in tumor cells. Synthesized ELP exhibited an inverse transition temperature (T(t)) of 40°C in serum with hyperthermia treatment and contained a lysine residue for conjugation with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[poly(ethylene-glycol)]-hydroxy succinamide, PEG MW 2000 (DSPE-PEG2000-NHS).

Topical application of liposomal cobalamin hydrogel for atopic dermatitis therapy.

Topical vitamin B12 was shown to be effective for atopic dermatitis. However, vitamin B12 itself is light sensitive and has low skin permeability, thus reducing its therapeutic effectiveness. In the present study, we prepared a liposomal hydrogel of adenosylcobalamin (AdCbl), a vitamin B12 derivative, and investigated possible beneficial effects of AdCbl on atopic dermatitis using an NC/Nga murine atopic dermatitis model.

Gadolinium-based cancer therapeutic liposomes for chemotherapeutics and diagnostics.

Gadolinium (Gd)-based cancer therapeutic liposomes can be used for chemotherapeutics and diagnostics. In this study, dual functional liposomes co-encapsulating doxorubicin (Dox) and Gd were prepared by Dox-transition metal complexation. Preparation conditions were optimized to obtain liposomes containing high concentrations of Dox and Gd.

Biocompatible Polyhydroxyethylaspartamide-based Micelles with Gadolinium for MRI Contrast Agents.

Biocompatible poly-[N-(2-hydroxyethyl)-d,l-aspartamide]-methoxypoly(ethyleneglycol)-hexadecylamine (PHEA-mPEG-C(16)) conjugated with 1,4,7,10-tetraazacyclododecan-1,4,7,10-tetraacetic acid-gadolinium (DOTA-Gd) via ethylenediamine (ED) was synthesized as a magnetic resonance imaging (MRI) contrast agent. Amphiphilic PHEA-mPEG-C(16)-ED-DOTA-Gd forms micelle in aqueous solution. All the synthesized materials were characterized by proton nuclear magnetic resonance ((1)H NMR).

Increased stability in plasma and enhanced cellular uptake of thermally denatured albumin-coated liposomes.

Liposomes are nano-scale vesicles that can be used as one of drug carriers. The liposomes are, however, plagued by rapid opsonization of them and hence making their circulation time in bloodstream to be shortened. In this study, cationically charged liposomes of which surface was modified with bovine serum albumin (BSA) were prepared by using electrostatic interaction between cationic liposomes and anionically charged BSA molecules at higher pH than isoelectric point (pI) of BSA.

Polyethylene glycol-complexed cationic liposome for enhanced cellular uptake and anticancer activity.

Liposomes as one of the efficient drug carriers have some shortcomings such as their relatively short blood circulation time, fast clearance from human body by reticuloendothelial system (RES) and limited intracellular uptake to target cells. In this study, polyethylene glycol (PEG)-complexed cationic liposomes (PCL) were prepared by ionic complex of cationically charged liposomes with carboxylated polyethylene glycol (mPEG-COOH). The cationic liposomes had approximately 98.

Disaccharide-modified liposomes and their in vitro intracellular uptake.

Sterically stabilized liposomes (SSL) were known to be accumulated passively in cancer due to the effect of enhanced permeability and retention (EPR). However, drug delivery via SSL to cancer seemed to show an insufficient improvement of chemotherapeutic efficacy. Herein, carbohydrate-binding proteins (lectins) of cell surface, which express on the plasmic membrane of many malignant cells, can be a good model of surface-modified liposomes.

Amphotericin B-entrapping lipid nanoparticles and their in vitro and in vivo characteristics.

Lipid nanoparticles (LNPs) as nano-scale drug carriers that can entrap poorly water-soluble drugs such as amphotericin B (AmB) in aqueous solution with high drug entrapment efficiency were developed and their in vitro and in vivo characteristics were investigated. The AmB-entrapping plain, anionic and PEG (polyethylene glycol)-LNPs were prepared by using spontaneous emulsification and solvent evaporation (SESE) method. Mean particle size of the AmB-entrapping LNPs ranged from 72.