type: misc

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en: 血清アルブミンに存在する超硫黄の解析と創薬応用

ja: 血清アルブミンに存在する超硫黄の解析と創薬応用

en: Journal of the Pharmaceutical Society of Japan

ja: 薬学雑誌


en: Polyethylene glycol (PEG): The nature, immunogenicity, and role in the hypersensitivity of PEGylated products

en: Journal of Controlled Release

ja: Journal of Controlled Release


en: The challenge to deliver oxaliplatin (l-OHP) to solid tumors: development of liposomal l-OHP formulations

en: Chemical & Pharmaceutical Bulletin

ja: Chemical & Pharmaceutical Bulletin


en: The new delivery strategy of albumin carrier utilizing the interaction with albumin receptors


en: Drug Delivery System for Refractory Cancer Therapy via an Endogenous Albumin Transport System


en: タンパクのPEG修飾によるPEG免疫応答の誘導

ja: タンパクのPEG修飾によるPEG免疫応答の誘導


en: Control of EPR effect by tumor-targeted NO donor via endogenous albumin transport system

ja: 内因性アルブミン輸送システムを利用した腫瘍選択的NO供与によるEPR効果の制御

en: A unique phenomenon in solid tumors, enhanced permeability and retention(EPR) effect, is very famous for the development of macromolecular anticancer therapy. However, cancers with low vascular permeability posed a challenge for these EPR based therapeutic systems. An intrinsic vascular modulator such as nitric oxide(NO) could augment the intrinsic EPR effect. We have demonstrated that S-nitrosated human serum albumin dimer(SNO-HSA Dimer) becomes an enhancer of the EPR effect in various tumor-bearing mice models. Here, we summarized the enhanced effect of SNO-HSA Dimer on the anticancer effect of two types of macromolecular anticancer drugs, namely PEGylated liposomal doxorubicin(Doxil®) and albumin bound paclitaxel nanoparticle(Abraxane®). In C26-bearing mice with highly permeable vasculature, SNO-HSA Dimer could increase tumor accumulation of these anticancer drugs and thereby their anticancer effects. Interestingly, the tumor accumulation of Doxil® in B16-bearing mice, which are characterized by a low permeable vasculature, increased more 6-fold in the presence of SNO-HSA Dimer, and the improved accumulation of Doxil® led to increased survival and decreased tumor volume. On the other hand, SNO-HSA Dimer also augmented the tumor growth inhibition of Abraxane® in low vascular permeability B16-bearing mice. Furthermore, Abraxane® combined with SNO-HSA Dimer showed higher antitumor activity and improved survival rate of SUIT2 human pancreatic cancer orthotopic model. We also showed that the administration of SNO-HSA Dimer had no effect on blood pressure, heart rate and biochemical parameters, suggesting that SNO-HSA Dimer alone is very safe. Accordingly, we conclude that SNO-HSA Dimer is promising for regulating the EPR effect and enhanced therapeutic effects of many macromolecular anticancer drugs.

ja: EPR効果は，高分子抗がん療法の開発の基礎となり得るが，低い血管透過性を有するがん領域では，このEPR効果のみでは十分な送達性が得られない．したがって，一酸化窒素(NO)のような血管調節分子で内因性EPR効果を増強することは極めて有望な戦略である．筆者らは，ヒト血清アルブミン二量体のS―ニトロソ化体(SNO―HSA Dimer)がEPR効果の増強剤であることを検討してきた．ここでは，すでに承認されたPEG化リポソーム・ドキソルビシン(Doxil®)およびアルブミン結合型パクリタキセル・ナノ粒子(Abraxane®)の2種類の高分子抗がん剤を用い，血管透過性が高いC26や血管透過性が低いB16担がんモデル，臨床病態に近いとされているSUIT2ヒト膵臓がん同所性モデルにて得られた結果を中心に報告する．

en: Drug Delivery System

ja: Drug Delivery System


en: Accelerated blood clearance (ABC) 現象における動物種差


en: ナノ粒子に対する補体活性化の功罪

ja: ナノ粒子に対する補体活性化の功罪


en: Poly-S-Nitrosated Albumin as a Safe and Effective Multifunctional Antitumor Agent: Characterization, Biochemistry and Possible Future Therapeutic Applications

en: Nitric oxide (NO) is a ubiquitous molecule involved in multiple cellular functions. Inappropriate production of NO may lead to disease states. To date, pharmacologically active compounds that release NO within the body, such as organic nitrates, have been used as therapeutic agents, but their efficacy is significantly limited by unwanted side effects. Therefore, novel NO donors with better pharmacological and pharmacokinetic properties are highly desirable. The S-nitrosothiol fraction in plasma is largely composed of endogenous S-nitrosated human serum albumin (Mono-SNO-HSA), and that is why we are testing whether this albumin form can be therapeutically useful. Recently, we developed SNO-HSA analogs such as SNO-HSA with many conjugated SNO groups (Poly-SNO-HSA) which were prepared using chemical modification. Unexpectedly, we found striking inverse effects between Poly-SNO-HSA and Mono-SNO-HSA. Despite the fact that Mono-SNO-HSA inhibits apoptosis, Poly-SNO-HSA possesses very strong proapoptotic effects against tumor cells. Furthermore, Poly-SNO-HSA can reduce or perhaps completely eliminate the multidrug resistance often developed by cancer cells. In this review, we forward the possibility that Poly-SNO-HSA can be used as a safe and effective multifunctional antitumor agent.

en: BioMed Research International

ja: BioMed Research International