• Journal of Pharmaceutical Investigation
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• 제40권4호
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• pp.201-212
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• 2010

Self-organized nanogels from polysaccharide derivatives offer a promising approach in treatment of cancer due to their flexibility in chemistry and their ability to improve the therapeutic index of a drug by modifying biodistribution by their preferential localization at target sites and lower distribution in normal healthy tissues. These properties have promoted studies of active cancer targeting by self-organized nanogels for even better accumulation in solid tumors. However although many researchers have reported their potential by using cell culture systems and small animal tumor models in cancer therapy, these nanogels need more decoration such as conjugation with targeting moiety and endowment of stimuli-sensitivity for precise targeting of the cancer site. In this review, we summarize the recent efforts in developing novel targeting approaches via active endocytosis and stimuli-sensitive systems responding to hyperthermic or acidic tumor pH conditions.

• BMB Reports
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• 제43권12호
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• pp.773-780
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• 2010

Cancers are still difficult targets despite recent advances in cancer therapy. Due to the heterogeneity of cancer, a single-treatment modality is insufficient for the complete elimination of cancer cells. Therapeutic strategies from various aspects are needed. Gene therapy has been expected to bring a breakthrough to cancer therapy, but it has not yet been successful. Gene therapy also should be combined with other treatments to enhance multiple therapeutic pathways. In this view, gene delivery vector itself should be equipped with intrinsic anti-cancer activities. HVJ (hemagglutinating virus of Japan; Sendai virus) envelope vector (HVJ-E) was developed to deliver therapeutic molecules. HVJ-E itself possessed anti-tumor activities such as the generation of anti-tumor immunities and the induction of cancer-selective apoptosis. In addition to the intrinsic anti-tumor activities, therapeutic molecules incorporated into HVJ-E enabled to achieve multi-modal therapeutic strategies in cancer treatment. Tumor-targeting HVJ-E was also developed. Thus, HVJ-E will be a novel promising tool for cancer treatment.

• 센서학회지
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• 제32권6호
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• pp.418-424
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• 2023

Natural killer (NK) cells play a crucial role in combating infections and tumors. However, their therapeutic application in solid tumors is hindered by challenges, such as limited lifespan, tumor penetration, and delivery precision. Our research introduces a novel ultrasonic actuation technique to navigate NK cells more effectively in the vascular system, particularly at vessel bifurcations where targeted delivery is most problematic. We use a hemispherical ultrasonic transducer array that generates phase-modulated traveling waves, focusing on an ultrasound beam to steer NK cells using blood-flow dynamics and a focused acoustic field. This method enables the precise obstruction of non-target vessels and efficiently directs NK cells toward the tumor site. The simulation results offer insights into the behavior of NK cells under various conditions of cell size, radiation pressure, and fluid velocity, which inform the optimization of their trajectories and increase targeting efficiency. The experimental results demonstrate the feasibility of this ultrasonic approach for enhancing NK cell targeting, suggesting a potential leap forward in solid tumor immunotherapy. This study represents a significant step in NK cell therapeutic strategies, offering a viable solution to the existing limitations and promising enhancement of the efficacy of cancer treatments.

• Journal of Ginseng Research
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• 제48권3호
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• pp.266-275
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• 2024

Cancer stem cells (CSCs) are a rare subpopulation of cancer cells that exhibit stem cell-like characteristics, including self-renewal and differentiation in a multi-stage lineage state via symmetric or asymmetric division, causing tumor initiation, heterogeneity, progression, and recurrence and posing a major challenge to current anticancer therapy. Despite the importance of CSCs in carcinogenesis and cancer progression, currently available anticancer therapeutics have limitations for eradicating CSCs. Moreover, the efficacy and therapeutic windows of currently available anti-CSC agents are limited, suggesting the necessity to optimize and develop a novel anticancer agent targeting CSCs. Ginseng has been traditionally used for enhancing immunity and relieving fatigue. As ginseng's long history of use has demonstrated its safety, it has gained attention for its potential pharmacological properties, including anticancer effects. Several studies have identified the bioactive principles of ginseng, such as ginseng saponin (ginsenosides) and non-saponin compounds (e.g., polysaccharides, polyacetylenes, and phenolic compounds), and their pharmacological activities, including antioxidant, anticancer, antidiabetic, antifatigue, and neuroprotective effects. Notably, recent reports have shown the potential of ginseng-derived compounds as anti-CSC agents. This review investigates the biology of CSCs and efforts to utilize ginseng-derived components for cancer treatment targeting CSCs, highlighting their role in overcoming current therapeutic limitations.

• IMMUNE NETWORK
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• 제22권1호
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• pp.9.1-9.23
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• 2022

In the past few decades, biological drugs and small molecule inhibitors targeting inflammatory cytokines, immune cells, and intracellular kinases have become the standard-of-care to treat autoimmune diseases. Inhibition of TNF, IL-6, IL-17, and IL-23 has revolutionized the treatment of autoimmune diseases, such as rheumatoid arthritis, ankylosing spondylitis, and psoriasis. B cell depletion therapy using anti-CD20 mAbs has shown promising results in patients with neuroinflammatory diseases, and inhibition of B cell survival factors is approved for treatment of systemic lupus erythematosus. Targeting co-stimulatory molecules expressed on Ag-presenting cells and T cells is also expected to have therapeutic potential in autoimmune diseases by modulating T cell function. Recently, small molecule kinase inhibitors targeting the JAK family, which is responsible for signal transduction from multiple receptors, have garnered great interest in the field of autoimmune and hematologic diseases. However, there are still unmet medical needs in terms of therapeutic efficacy and safety profiles. Emerging therapies aim to induce immune tolerance without compromising immune function, using advanced molecular engineering techniques.

• Molecules and Cells
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• 제41권11호
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• pp.933-942
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• 2018

Traditionally, small-molecule or antibody-based therapies against human diseases have been designed to inhibit the enzymatic activity or compete for the ligand binding sites of pathological target proteins. Despite its demonstrated effectiveness, such as in cancer treatment, this approach is often limited by recurring drug resistance. More importantly, not all molecular targets are enzymes or receptors with druggable 'hot spots' that can be directly occupied by active site-directed inhibitors. Recently, a promising new paradigm has been created, in which small-molecule chemicals harness the naturally occurring protein quality control machinery of the ubiquitin-proteasome system to specifically eradicate disease-causing proteins in cells. Such 'chemically induced protein degradation' may provide unprecedented opportunities for targeting proteins that are inherently undruggable, such as structural scaffolds and other non-enzymatic molecules, for therapeutic purposes. This review focuses on surveying recent progress in developing E3-guided proteolysis-targeting chimeras (PROTACs) and small-molecule chemical modulators of deubiquitinating enzymes upstream of or on the proteasome.

• Journal of Ginseng Research
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• 제44권3호
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• pp.386-398
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• 2020

Tissue fibrosis is an eventual pathologic change of numerous chronic illnesses, which is characterized by resident fibroblasts differentiation into myofibroblasts during inflammation, coupled with excessive extracellular matrix deposition in tissues, ultimately leading to failure of normal organ function. Now, there are many mechanistic insights into the pathogenesis of tissue fibrosis, which facilitate the discovery of effective antifibrotic drugs. Moreover, many chronic diseases remain a significant clinical unmet need. For the past five years, many research works have undoubtedly addressed the functional dependency of ginsenosides in different types of fibrosis and the successful remission in various animal models treated with ginsenosides. Caveolin-1, interleukin, thrombospondin-1 (TSP-1), liver X receptors (LXRs), Nrf2, microRNA-27b, PPARδ-STAT3, liver kinase B1 (LKB1)-AMPK, and TGF-β1/Smads are potential therapy targeting using ginsenosides. Ginsenosides can play a targeting role and suppress chronic inflammatory response, collagen deposition, and epitheliale-mesenchymal transition (EMT), as well as myofibroblast activation to attenuate fibrosis. In this report, our aim was to focus on the therapeutic prospects of ginsenosides in fibrosis-related human diseases making use of results acquired from various animal models. These findings should provide important therapeutic clues and strategies for the exploration of new drugs for fibrosis treatment.

• Asian Pacific Journal of Cancer Prevention
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• 제15권24호
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• pp.10557-10563
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• 2015

It is well known that conventional chemotherapy and radiation therapy can result in toxicity to both normal cells and tumor cells, which causes limitations in the application of these therapeutic strategies for cancer control. Novel and effective therapeutic strategies for cancers with no or low toxicity for normal cells are a high priority. Therefore, natural products with anticancer activity have gained more and more attention due to their favorable safety and efficacy profiles. Pre-clinical and clinical studies have demonstrated that several representative natural compounds such as resveratrol, epigallocatechin-3-gallate, curcumin, allicin and ginsenosides have obvious anticancer potential. In this article, we summarize autophagy-associated targeting pathways of such natural products for inducing the death of cancer cells, and discuss the core autophagic pathways involved in cancer treatments. Recent advances in the discovery, evaluation and exploitation of natural compounds as therapeutic agents for cancers will provide references and support in pre-clinical and clinical application of novel natural drugs for the treatment of primary and metastatic tumors in the future.

• The Korean Journal of Pain
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• 제22권1호
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• pp.1-15
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• 2009

Neuropathic pain is often refractory to intervention because of the complex etiology and an incomplete understanding of the mechanisms behind this type of pain. Glial cells, specifically microglia and astrocytes, are powerful modulators of pain and new targets of drug development for neuropathic pain. Glial activation could be the driving force behind chronic pain, maintaining the noxious signal transmission even after the original injury has healed. Glia express chemokine, purinergic, toll-like, glutaminergic and other receptors that enable them to respond to neural signals, and they can modulate neuronal synaptic function and neuronal excitability. Nerve injury upregulates multiple receptors in spinal microglia and astrocytes. Microglia influence neuronal communication by producing inflammatory products at the synapse, as do astrocytes because they completely encapsulate synapses and are in close contact with neuronal somas through gap junctions. Glia are the main source of inflammatory mediators in the central nervous system. New therapeutic strategies for neuropathic pain are emerging such as targeting the glial cells, novel pharmacologic approaches and gene therapy. Drugs targeting microglia and astrocytes, cytokine production, and neural structures including dorsal root ganglion are now under study, as is gene therapy. Isoform-specific inhibition will minimize the side effects produced by blocking all glia with a general inhibitor. Enhancing the anti-inflammatory cytokines could prove more beneficial than administering proinflammatory cytokine antagonists that block glial activation systemically. Research on therapeutic gene transfer to the central nervous system is underway, although obstacles prevent immediate clinical application.

• Nuclear Medicine and Molecular Imaging
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• 제42권5호
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• pp.337-346
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• 2008

Applications of nanotechnology in the medical field have provided the fundamentals of tremendous improvement in precise diagnosis and customized therapy. Recent advances in nanomedicine have led to establish a new concept of theragnosis, which utilizes nanomedicines as a therapeutic and diagnostic tool at the same time. The development of high affinity nanoparticles with large surface area and functional groups multiplies diagnostic and therapeutic capacities. Considering the specific conditions related to the disease of individual patient, customized therapy requires the identification of disease target at the cellular and molecular level for reducing side effects and enhancing therapeutic efficiency. Well-designed nanoparticles can minimize unnecessary exposure of cytotoxic drugs and maximize targeted localization of administrated drugs. This review will focus on major pharmaceutical nanomaterials and nanoparticles as key components of designing and surface engineering for targeted theragnostic drug development.