Multifunctional elastin-like polypeptide nanocarriers for efficient miRNA delivery in cancer therapy.

Background: The exogenous delivery of miRNA to mimic and restore miRNA-34a activity in various cancer models holds significant promise in cancer treatment. Nevertheless, its effectiveness is often impeded by challenges, including a short half-life, propensity for off-target accumulation, susceptibility to inactivation by blood-based enzymes, concerns regarding patient safety, and the substantial cost associated with scaling up. As a means of overcoming these barriers, we propose the development of miRNA-loaded Tat-A86 nanoparticles by virtue of Tat-A86's ability to shield the loaded agent from external environmental factors, reducing degradation and inactivation, while enhancing circulation time and targeted accumulation.

Therapeutic Effect of IL-4 Receptor-Targeting Pro-Apoptotic Peptide (AP1-ELP-KLAK) in Glioblastoma Tumor Model.

Background: Thermal-responsive self-assembled elastin-like polypeptide (ELP)-based nanoparticles are an emerging platform for controlled delivery of therapeutic peptides, proteins and small molecular drugs. The antitumor effect of bioengineered chimeric polypeptide AP1-ELP-KLAK containing an interleukin-4 receptor (IL-4R) targeting peptide and pro-apoptotic peptide (KLAKLAK) was evaluated in glioblastoma (GBM) and .

Methods And Results: Herein, the therapeutic effect of AP1-ELP-KLAK was tested in advanced, and less curable glioblastoma cells with higher expression of IL-4R.

Targeting of Cisplatin-Resistant Melanoma Using a Multivalent Ligand Presenting an Elastin-like Polypeptide.

Acquired drug resistance is a common occurrence and the main cause of melanoma treatment failure. Melanoma cells frequently developed resistance against cisplatin during chemotherapy, and thus, targeting delivery systems have been devised to decrease drug resistance, increase therapeutic efficacy, and reduce side effects. We genetically engineered a macromolecular carrier using the recursive directional ligation method that specifically targets cisplatin-resistant (Cis-R) melanoma.

Effects of molecular weight and structural conformation of multivalent-based elastin-like polypeptides on tumor accumulation and tissue biodistribution.

In order to improve clinical outcomes for novel drug delivery systems, distinct optimization of size, shape, multifunctionality, and site-specificity are of utmost importance. In this study, we designed various multivalent elastin-like polypeptide (ELP)-based tumor-targeting polymers in which multiple copies of IL-4 receptor (IL-4R)-targeting ligand (AP1 peptide) were periodically incorporated into the ELP polymer backbone to enhance the affinity and avidity towards tumor cells expressing high levels of IL-4R. Several ELPs with different molecular sizes and structures ranging from unimer to micelle-forming polymers were evaluated for their tumor accumulation as well as bio-distribution patterns.

Exogenous exosomes from mice with acetaminophen-induced liver injury promote toxicity in the recipient hepatocytes and mice.

Exosomes are small extracellular membrane vesicles released from endosomes of various cells and could be found in most body fluids. The main functions of exosomes have been recognized as important mediators of intercellular communication and as potential biomarkers of various disease states. This study investigated whether exogenous exosomes from mice with acetaminophen (APAP)-induced liver injury can damage the recipient hepatic cells or promote hepatotoxicity in mice.

PSP1, a Phosphatidylserine-Recognizing Peptide, Is Useful for Visualizing Radiation-Induced Apoptosis in Colorectal Cancer In Vitro and In Vivo.

Accurate and timely visualization of apoptotic status in response to radiation is necessary for deciding whether to continue radiation or change to another mode of treatment. This is especially critical in patients with colorectal cancer, which requires a delicate combination of surgery, radiation, and chemotherapy in order to achieve optimal outcome. In this study, we investigated the potential of phosphatidylserine-recognizing peptide 1 (PSP1) as an apoptosis-targeting probe, which identifies phosphatidylserine on cell surfaces.

Application of Bld-1-Embedded Elastin-Like Polypeptides in Tumor Targeting.

Expression of various molecules on the surface of cancer cells compared to normal cells creates a platform for the generation of various drug vehicles for targeted therapy. Multiple interactions between ligands and their receptors mediated by targeting peptide-modified polymer could enable simultaneous delivery of a drug selectively to target tumor cells, thus limiting side effects resulting from non-specific drug delivery. In this study, we synthesized a novel tumor targeting system by using two key elements: (1) Bld-1 peptide (SNRDARRC), a recently reported bladder tumor targeting peptide identified by using a phage-displayed peptide library, and (2) ELP, a thermally responsive polypeptide.

A targeted ferritin-microplasmin based thrombolytic nanocage selectively dissolves blood clots.

The use of thrombolytic therapies is limited by an increased risk of systemic hemorrhage due to lysis of hemostatic clots. We sought to develop a plasmin-based thrombolytic nanocage that efficiently dissolves the clot without causing systemic fibrinolysis or disrupting hemostatic clots. Here, we generated a double chambered short-length ferritin (sFt) construct that has an N-terminal region fused to multivalent clot targeting peptides (CLT: CNAGESSKNC) and a C-terminal end fused to a microplasmin (μPn); CLT recognizes fibrin-fibronectin complexes in clots, μPn efficiently dissolves clots, and the assembly of double chambered sFt (CLT-sFt-μPn) into nanocage structure protects the activated-μPn from its circulating inhibitors.

Circulating Plasma and Exosomal microRNAs as Indicators of Drug-Induced Organ Injury in Rodent Models.

This study was performed to evaluate whether microRNAs (miRNAs) in circulating exosomes may serve as biomarkers of drug-induced liver, kidney, or muscle-injury. Quantitative PCR analyses were performed to measure the amounts of liver-specific miRNAs (miR-122, miR-192, and miR-155), kidney-specific miR-146a, or muscle-specific miR-206 in plasma and exosomes from mice treated with liver, kidney or muscle toxicants. The levels of liver-specific miRNAs in circulating plasma and exosomes were elevated in acetaminophen-induced liver injury and returned to basal levels by treatment with antioxidant -acetyl-cysteine.

Multivalent Targeting Based Delivery of Therapeutic Peptide using AP1-ELP Carrier for Effective Cancer Therapy.

Elastin-like polypeptide (ELP)-based drug delivery has been utilized for various applications including cancer therapies for many years. Genetic incorporation of internalization ligands and cell-targeting peptides along with ELP polymer enhanced tumor accumulation and retention time as well as stability and activities of the drug conjugates. Herein, we described a unique delivery system comprised of genetically engineered ELP incorporated with multiple copies of IL-4 receptor targeting peptide (AP1) periodically and proapoptotic peptide (KLAKLAK) referred to as AP1-ELP-KLAK.

Association between perfluorooctanoic acid exposure and degranulation of mast cells in allergic inflammation.

Perfluorooctanoic acid (PFOA) has wide applications, including as a raw material for converted paper and packaging products. With the widespread use of PFOA, concerns regarding its potential environmental and health impacts have increased. In spite of the known hepatotoxicity and genotoxicity of PFOA, correlation with PFOA and allergic inflammation is not well known.

Probing amyloid beta-induced cell death using a fluorescence-peptide conjugate in Alzheimer's disease mouse model.

With the increasing worldwide incidence of Alzheimer's disease (AD), there is a critical need for the discovery of more effective diagnostic methods. However, development of diagnostic tools in AD has been hindered by obstacles such as the absence of exact biomarkers. Apoptosis caused by amyloid-β (Aβ) plays an important role in AD pathology; therefore, provides an attractive biological target for the diagnosis of AD.

1,2,4,5-Tetramethoxybenzene Suppresses House Dust Mite-Induced Allergic Inflammation in BALB/c Mice.

Background: Atopic dermatitis (AD) is the most common allergic inflammatory skin disease. The activation of innate immunity by house dust mite (Dermatophagoides farinae extract, DFE) allergen plays an important role in the pathogenesis of AD. We previously showed the inhibitory effect of an extract of Amomum xanthioides on allergic diseases, and isolated 1,2,4,5-tetramethoxybenzene (TMB) as a major active component.

Development of a novel microbubble-liposome complex conjugated with peptide ligands targeting IL4R on brain tumor cells.

Gas (SF6)-filled microbubbles (MBs) were prepared by emulsion and solvent-evaporation method. The prepared MBs were further conjugated with doxorubicin (Dox)-loaded nano-sized liposome and peptide ligands to interleukin-4 receptor (IL4R) for targeting brain tumor cells. The final MB-liposome (Dox)-IL4R targeting peptide ligand [MB-Lipo (Dox)-IL4RTP] had a spherical structure with the mean size of 1,500 nm.

Designing Peptide Bunches on Nanocage for Bispecific or Superaffinity Targeting.

Ferritin cage nanoparticles are promising platforms for targeted delivery of imaging and therapeutic agents because their cage structure can accommodate small molecules and their surfaces can be decorated with multiple functionalities. However, selective targeting is still a challenge for translating ferritin-based nanomedicines into the clinic, especially for heterogeneous diseases such as cancer. Targeting peptides can be genetically fused onto the surface of a ferritin cage, forming peptide bunches on nanocages (PBNCs) that offer synergistic increases in binding avidity.

Poly-paclitaxel/cyclodextrin-SPION nano-assembly for magnetically guided drug delivery system.

This work demonstrates the development of magnetically guided drug delivery systems and its potential on efficient anticancer therapy. The magnetically guided drug delivery system was successfully developed by utilizing superparamagnetic iron oxide nanoparticle, β-cyclodextrin, and polymerized paclitaxel. Multivalent host-guest interactions between β-cyclodextrin-conjugated superparamagnetic iron oxide nanoparticle and polymerized paclitaxel allowed to load the paclitaxel and the nanoparticle into the nano-assembly.

Double-Chambered Ferritin Platform: Dual-Function Payloads of Cytotoxic Peptides and Fluorescent Protein.

Ferritin cage nanoparticles are promising platforms for targeted delivery of imaging and therapeutic agents. One of the main advantages of cage nanoparticles is the ability to display multiple functionalities through genetic modification so as to achieve desired therapeutic or diagnostic functions. Ferritin complexes formed from short ferritin (sFt) lacking the fifth helix can accommodate dual peptide and protein functionalities on N- and C-terminal sites in sFt monomers.

A novel method to detect articular chondrocyte death during early stages of osteoarthritis using a non-invasive ApoPep-1 probe.

Introduction: Current methods for early diagnosis of osteoarthritis (OA) are limited. We assessed whether in vivo detection of chondrocyte death by ApoPep-1 (CQRPPR), a peptide that binds to histone H1 of apoptotic and necrotic cells, could be used to detect the initiation of OA.

Methods: Apoptosis-induced ATDC5 cells were labeled with Annexin V and ApoPep-1.

An Electrochemical Biosensor Based on a Myoglobin-specific Binding Peptide for Early Diagnosis of Acute Myocardial Infarction.

In this study, a simple, highly sensitive electrochemical biosensor for myoglobin was developed using a myoglobin-specific binding peptide as a sensing probe. A peptide (Myo-3R7, CPSTLGASC, 838 Da) identified by phage display and that specifically binds to myoglobin was covalently immobilized on a gold electrode functionalized via a dithiobis(succinimidyl propionate) (DSP) self-assembled monolayer (SAM). The peptide immobilization was confirmed with fluorescence microarray scanning and cyclic voltammetry (CV).

Enhanced delivery of liposomes to lung tumor through targeting interleukin-4 receptor on both tumor cells and tumor endothelial cells.

A growing body of evidence suggests that pathological lesions express tissue-specific molecular targets or biomarkers within the tissue. Interleukin-4 receptor (IL-4R) is overexpressed in many types of cancer cells, including lung cancer. Here we investigated the properties of IL-4R-binding peptide-1 (IL4RPep-1), a CRKRLDRNC peptide, and its ability to target the delivery of liposomes to lung tumor.

Hyaluronic acid nanoparticles for active targeting atherosclerosis.

For the effective diagnosis and therapy of atherosclerosis, there is a pressing need to develop the carrier which can specifically deliver the agents to the pathological site. Since the representative hallmark of atherosclerosis in its pathogenic process is the over-expression of the receptors for hyaluronic acid (HA) such as stabilin-2 and CD44, we herein investigated the potential of HA nanoparticles (HA-NPs) as the carrier for active targeting atherosclerosis. From in vitro cellular uptake tests, it was revealed that HA-NPs were selectively taken up by the cells over-expressing stabilin-2 or CD44.

Advantages of the phosphatidylserine-recognizing peptide PSP1 for molecular imaging of tumor apoptosis compared with annexin V.

A number of peptide-based indicators have been identified and reported as potential apoptosis probes, offering great promise for early assessment of therapeutic efficacy in several types of cancer. Direct comparison of the newly developed probes with previously used ones would be an important step in assessing possible applications. Here, we compared the newly identified peptide-based phosphatidylserine (PS) indicator PSP1 (CLSYYPSYC) with annexin V, a common probe for molecular imaging of apoptotic cells, with respect to PS binding kinetics, apoptotic cell-targeting ability, and the efficacy of homing to apoptotic tumor cells in a mouse model after treatment with the anticancer agent camptothecin.

Design of a multicomponent peptide-woven nanocomplex for delivery of siRNA.

We developed and tested a multicomponent peptide-woven siRNA nanocomplex (PwSN) comprising different peptides designed for efficient cellular targeting, endosomal escape, and release of siRNA. To enhance tumor-specific cellular uptake, we connected an interleukin-4 receptor-targeting peptide (I4R) to a nine-arginine peptide (9r), yielding I4R-9r. To facilitate endosomal escape, we blended endosomolytic peptides into the I4R-9r to form a multicomponent nanocomplex.

Recurrence and cancer-specific survival according to the expression of IL-4Rα and IL-13Rα1 in patients with oral cavity cancer.

Background: Interleukin-4 (IL-4) and interleukin-13 (IL-13) are anti-inflammatory and immunomodulatory cytokines that play crucial roles in cancer progression. However, the clinical significance of the expression of these cytokines and their receptors (IL-4R) in oral cavity squamous cell carcinoma (OSCC) is unknown. Therefore, we evaluated the expression of IL-4R in OSCC specimens by immunohistochemistry (IHC) and analysed its relationship to recurrence and survival.

Apoptosis imaging studies in various animal models using radio-iodinated peptide.

Apoptosis has a role in many medical disorders and treatments; hence, its non-invasive evaluation is one of the most riveting research topics. Currently annexin V is used as gold standard for imaging apoptosis. However, several drawbacks, including high background, slow body clearance, make it a suboptimum marker for apoptosis imaging.