• Title/Summary/Keyword: Triggering drug release

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Magnetic Nanochain-Based Smart Drug Delivery System with Remote Tunable Drug Release by a Magnetic Field

  • Byunghoon Kang;Moo-Kwang Shin;Seungmin Han;Ilyoung Oh;Eunjung Kim;Joseph Park;Hye Young Son;Taejoon Kang;Juyeon Jung;Yong-Min Huh;Seungjoo Haam;Eun-Kyung Lim
    • BioChip Journal
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    • v.16
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    • pp.280-290
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    • 2020
  • Considerable attention is given to drug delivery technology that efficiently delivers appropriate levels of drug molecules to diseased sites with significant therapeutic efficacy. Nanotechnology has been used to develop various strategies for targeted drug delivery, while controlling the release of drugs because of its many benefits. Here, a delivery system was designed to control drug release by external magnetic fields using porous silica and magnetic nanoparticles. Magnetic nanochains (MNs) of various lengths (MN-1: 1.4 ± 0.8 ㎛, MN-2: 2.2 ± 1.1 ㎛, and MN-3: 5.3 ± 2.0 ㎛) were synthesized by controlling the exposure time of the external magnetic force in magnetic nanoaggregates (MNCs). Mesoporous silica-coated magnetic nanochains (MSMNs) (MSMN-1, MSMN-2, and MSMN-3) were prepared by forming a porous silica layer through sol-gel polymerization. These MSMNs could load the drug doxorubicin (DOX) into the silica layer (DOX-MSMNs) and control the release behavior of the DOX through an external rotating magnetic field. Simulations and experiments were used to verify the motion and drug release behavior of the MSMNs. Furthermore, a bio-receptor (aptamer, Ap) was introduced onto the surface of the DOX-MSMNs (Ap-DOX-MSMNs) that could recognize specific cancer cells. The Ap-DOX-MSMNs demonstrated a strong therapeutic effect on cancer cells that was superior to that of the free DOX. The potent ability of these MSMNs as an external stimulus-responsive drug delivery system was proven.

Poly(benzyl-L-histidine)-b-Poly(ethylene glycol) Micelle Engineered for Tumor Acidic pH-Targeting, in vitro Evaluation

  • Lee, Eun-Seong;Youn, Yu-Seok
    • Bulletin of the Korean Chemical Society
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    • v.29 no.8
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    • pp.1539-1544
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    • 2008
  • A polymeric micelle, based on the poly(benzyl-L-histidine)-b-poly(ethylene glycol) (polyBz-His-b-PEG) diblock copolymer, was designed as a tumor-specific targeting carrier. The micelles (particle size: 67-80 nm, critical micelle concentration (CMC); 2-3 $\mu$g/mL) were formed from the diafilteration method at pH 7.4, as a result of self-assembly of the polyBz-His block at the core and PEG block on the shell. Removing benzyl (Bz) group from polyBz-His block provided pH-sensitivity of the micellar core; the micelles were physically destabilized in the pH range of pH 7.4-5.5, depending on the content of the His group free from Bz group. The ionization of His group at a slightly acidic pH promoted the deformation of the interior core. These pHdependent physical changes of the micelles provide the mechanism for pH-triggering anticancer drug (e.g., doxorubicin: DOX) release from the micelle in response to the tumor’s extracellular pH range (pH 7.2-6.5).

Application of Stimuli-responsive Chitosan Micelles for Improved Therapeutic Efficiency of Anticancer Agents (항암제의 치료 효율성을 높이기 위한 다양한 자극 응답성 물질이 개질된 키토산 마이셀의 응용성 고찰)

  • Jeong, Gyeong-Won;Park, Jun-Kyu;Nah, Jae-Woon
    • Applied Chemistry for Engineering
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    • v.29 no.2
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    • pp.147-154
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    • 2018
  • Currently, to overcome low therapeutic efficiencies and side effects of anticancer agents, the study of drug carrier based on polymers have been consistently investigated. Although the traditional drug carrier based on polymers displayed an excellent result and significant progress, there has been a problem with the side effect and low therapeutic efficiency because of the premature drug release before reached to the targeted region by the low stability in blood stream and sustained drug release. In this review article, to improve the problem of inefficient drug release, methods were suggested, which can maximize the therapeutic efficiency by increasing the stability in the blood stream and triggering drug release at the target site by introducing a stimuli-responsive substance to the non-toxic and biocompatible natural polymer chitosan.

The role of necroptosis in the treatment of diseases

  • Cho, Young Sik
    • BMB Reports
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    • v.51 no.5
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    • pp.219-224
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    • 2018
  • Necroptosis is an emerging form of programmed cell death occurring via active and well-regulated necrosis, distinct from apoptosis morphologically, and biochemically. Necroptosis is mainly unmasked when apoptosis is compromised in response to tumor necrosis factor alpha. Unlike apoptotic cells, which are cleared by macrophages or neighboring cells, necrotic cells release danger signals, triggering inflammation, and exacerbating tissue damage. Evidence increasingly suggests that programmed necrosis is not only associated with pathophysiology of disease, but also induces innate immune response to viral infection. Therefore, necroptotic cell death plays both physiological and pathological roles. Physiologically, necroptosis induce an innate immune response as well as premature assembly of viral particles in cells infected with virus that abrogates host apoptotic machinery. On the other hand, necroptosis per se is detrimental, causing various diseases such as sepsis, neurodegenerative diseases and ischemic reperfusion injury. This review discusses the signaling pathways leading to necroptosis, associated necroptotic proteins with target-specific inhibitors and diseases involved. Several studies currently focus on protective approaches to inhibiting necroptotic cell death. In cancer biology, however, anticancer drug resistance severely hampers the efficacy of chemotherapy based on apoptosis. Pharmacological switch of cell death finds therapeutic application in drug- resistant cancers. Therefore, the possible clinical role of necroptosis in cancer control will be discussed in brief.

Kenalog modified by ionizing radiation induces intrinsic apoptosis mediated by elevated levels of reactive oxygen species in melanoma cancer

  • REMIGIUS AMBROSE KAWALA;FATUMA JUMAPILI RAMADHANI;HYO JIN CHOI;EUN-HEE LEE;CHUL-HONG PARK;BYUNG YEOUP CHUNG;HYOUNG-WOO BAI
    • Oncology Letters
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    • v.41 no.3
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    • pp.1837-1850
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    • 2019
  • Kenalog is a synthetic glucocorticoid drug used to treat various cancers including ocular and choroidal melanoma. However, the drug achieves rarely sustainable results for patients. To overcome this difficulty, the structure of Kenalog was altered by ionizing radiation (IR) to develop a more effective anticancer agent for treatment of various skin cancers. The anticancer effect of modified Kenalog (Kenalog-IR) was assessed in melanoma cancer cells in vitro. The assessment of mitochondrial functions by MTT assay revealed significant inhibition of melanoma cancer cell viability by Kenalog-IR compared to Kenalog. Moreover, Kenalog-IR-induced apoptotic cell death was associated with the intrinsic mitochondrial pathway by triggering the release of intrinsic apoptosis molecules through activation of caspase-related molecules in concentration and time-dependent manners. Furthermore, it was observed that Kenalog-IR-induced apoptosis was associated with the generation of reactive oxygen species (ROS) with increased G2/M cell cycle arrest. Collectively, Kenalog-IR may be a potential suppressor of skin-related cancer in particular melanoma cancer.