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对癌症代谢和信号转导途径的深入了解，有助于开发更有效的治疗方法。例如，许多类型的癌细胞中葡萄糖消耗的增加是由II型己糖激酶(HKII)的过表达调控的。事实上，肿瘤细胞即使在有氧条件下也表现出活跃的糖酵解，这被称为瓦伯格效应[1]。这种独特的途径使癌细胞具有选择性优势，如增强增殖、侵袭和转移[2]。糖酵解进一步通过支持癌细胞不间断的生长而提供选择性优势。例如，肿瘤细胞中较高的糖酵解率已被证明会促进对化疗药物的耐药性。例如，在宫颈癌细胞系HeLa中，丙酮酸脱氢酶激酶(PDK)亚型PDK1和PDK3已被证明对化疗药物[3]具有耐药性。己糖激酶是一种关键的糖酵解酶，它催化糖酵解途径的第一步，有助于表现出Warburg效应。这种酶将一个磷酸基从ATP转移到葡萄糖，形成葡萄糖-6-磷酸。此外，HKII与外膜蛋白电压依赖性阴离子通道(VDAC)相互作用。 It blocks mitochondrial inter membrane space proteins release and prevents activation of the apoptotic process [4]. Whereas , HKII prevents association of pro-apoptotic BcL-2 family member proteins (Bad, Bak, Bax) with the mitochondrial permeability transition pore (mtPTP) complex; pro-apoptotic factor association is necessary for mitochondrial permeability transition and cytochrome c release (the apoptotic cascade) [5]. This observation has led to the development of therapeutic strategies such as use of small molecules for inhibition of glycolytic activity in cancer cells [6]. In this case, lonidamine, 3-bromopyruvate (3-BrPA) and 3-BrOP (3-bromo-2-oxopropionate-1 -propyl ester) [7,8], are used as HK-II inhibitors in the early stages of treatment, can effectively inhibit glycolysis. The crucial problem for using them in clinical application is related to their interaction with normal cells, especially erythrocytes [9]. Thus, there is an urgent need to encapsulate them inside smart carriers having efficient strategies from size, shape, and targeted for cancer cells [10]. In our previous report, 3BrPA attached Poly(allylamine) hydrochloride was entrapped inside CaCO3 rods during their fabrication. [11]. However, non-specific, passive, targeting, carriers can result in uptake by healthy cells. This can be minimized by the active targeting of the therapy, In our recent work, targeted hybrid lipid polymer as alternate assembly structure instead of liposomes is fabricated. Their positive attributes make them a promising drug delivery vehicle for further in vivo evaluation. Hybrid polymeric protein carriers (HPPNCs) were assembled by using chitosan, oleic acid and BSA-FA to form core shell structure [12].

参考文献

1. Kaelin WG Jr, Thompson CB(2010)问与答:癌症:来自细胞代谢的线索。自然465: 562 - 564。［Crossref］
2. Gillies RJ, Robey I, Gatenby RA(2008)癌症葡萄糖代谢增加的原因和后果。J诊断49: 24 s-42s。［Crossref］
3. 卢春旺，林淑玲，陈克峰，赖云英，蔡淑娟(2008)缺氧诱导因子-1诱导丙酮酸脱氢酶激酶-3促进代谢开关和耐药。J临床生物化学283: 28106 - 28114。［Crossref］
4. Pastorino JG, Hoek JB, Shulga N(2005)激活糖原合成酶激酶3_通过磷酸化电压依赖性阴离子通道破坏己糖激酶II与线粒体的结合，并增强化疗诱导的细胞毒性。癌症Res65: 10545 - 10554。［Crossref］
5. Mathupala SP, Ko YH, Pedersen PL(2006)己糖激酶II:癌症的双刃剑，当结合到线粒体时，既是恶性肿瘤的促进者，也是恶性肿瘤的守门人。致癌基因25日:4777 - 4786。［Crossref］
6. Pelicano H, Martin DS, Xu RH, Huang P(2006)糖酵解抑制治疗肿瘤。致癌基因25日:4633 - 4646。［Crossref］
7. 7.陈志，吕伟，黄鹏(2007)华堡效应及其临床意义。J Bioenerg Biomembr39: 267 - 274。［Crossref］
8. 靶向白血病糖酵解:一种新型抑制剂3-BrOP联合雷帕霉素。Leuk Res5: 814 - 820。[Crossref］
9. Sadowska-Bartosz I, Soszynski M, Ulaszewski S, KoY, Bartosz G(2014) 3-溴丙酮酸在人红细胞膜上的转运。细胞Mol Biol Lett19日:201 - 214。［Crossref］
10. Hanafy NAN, Quarta A, Di Corato R, Dini L, Nobile C, et al.(2017)混合聚合蛋白纳米载体(HPPNC)靶向递送TGFβ抑制剂至肝癌细胞。医学杂志28号:120 (Crossref］
11. Hanafy NAN, De Giorgi ML, Nobile C, Cascione MF, Rinaldi R, et al. (2016) CaCO_3.作为壳聚糖-聚半乳糖醛酸载体的溴丙酮酸输送棒。Sci副词板牙8: 514 - 523。
12. Hanafy NA, Dini L, Citti C, Cannazza G, Leporatti S(2018)通过使用微/纳米脂质溴代脲壳聚糖载体抑制糖酵解，作为一种有前景的工具，改善肝癌的治疗。纳米材料(巴塞尔)8: [Crossref］