旨在提高癌癥治療的結(jié)果的抗血管生成藥物和納米藥物兩種治療策略的結(jié)合只有當(dāng)使用最小納米藥物的時(shí)候，這兩種治療策略的結(jié)合才可能是成功的,。美國(guó)馬薩諸塞州總醫(yī)院（MGH）研究人員在《自然納米技術(shù)》上發(fā)表文章稱(chēng)：腫瘤組織內(nèi)血管正?；芴岣邩?biāo)準(zhǔn)化療藥物的傳遞，可以阻止更大的納米藥物分子進(jìn)入腫瘤血管,。
麻省總醫(yī)院放射腫瘤科斯蒂爾腫瘤生物學(xué)實(shí)驗(yàn)室Vikash P. Chauhan說(shuō)：我們發(fā)現(xiàn)血管正?；粌H促進(jìn)了最小的納米藥物進(jìn)入癌細(xì)胞，我們還發(fā)現(xiàn)最小的納米藥物天生就比大的納米藥物能更容易穿透腫瘤組織,，這表明小的納米藥物可能是治療癌癥的理想選擇,。
腫瘤需要生成自己血管以供應(yīng)能量，但腫瘤血管往往雜亂無(wú)章,。腫瘤血管不僅防止了化療藥物傳遞到細(xì)胞無(wú)法靠近腫瘤血管,，并且血管的血漿滲漏性增加腫瘤內(nèi)的壓力能進(jìn)一步減少藥物滲透到腫瘤組織能的能力。通過(guò)抑制血管生成藥物的治療可以減少這些異常,，這一過(guò)程被稱(chēng)為血管正?；渑c標(biāo)準(zhǔn)化療藥物聯(lián)合運(yùn)用已被證明可以改善某些癌癥的治療。
納米藥物實(shí)際上是依據(jù)利用腫瘤血管異常設(shè)計(jì)的,。標(biāo)準(zhǔn)化療藥物的分子約一納米,，納米分子從10到100倍大，不足以穿透正常組織的血管毛孔,，但卻能通過(guò)超大的毛孔傳遞倒腫瘤血管中,。
麻省總醫(yī)院團(tuán)隊(duì)編寫(xiě)了一個(gè)數(shù)學(xué)模型預(yù)測(cè)，腫瘤血管壁異常大的毛孔導(dǎo)致腫瘤內(nèi)壓力增加,，阻礙藥物進(jìn)入腫瘤內(nèi),，抗血管生成治療減少毛孔孔徑減少瘤內(nèi)壓力，使得這些藥物分子通過(guò)大小合適的毛孔進(jìn)入腫瘤血管,。
美國(guó)哈佛大學(xué)工程與應(yīng)用科學(xué)專(zhuān)業(yè)學(xué)生Chauhan說(shuō)：目前在臨床試驗(yàn)中使用或多種抗癌納米藥物,，我們的研究結(jié)果表明小的納米藥物結(jié)合抗血管生成療法可能有協(xié)同效應(yīng)。斯蒂爾實(shí)驗(yàn)室主任Rakesh K. Jain博士表示：我們的研究提供指引上如何結(jié)合納米藥物與抗血管生成藥物,。（生物谷：Bioon.com）
doi:10.1038/nnano.2012.45
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Normalization of tumour blood vessels improves the delivery of nanomedicines in a size-dependent manner
Vikash P. Chauhan,Triantafyllos Stylianopoulos,John D. Martin,Zoran Popovi,Ou Chen,Walid S. Kamoun,Moungi G. Bawendi,Dai Fukumura& Rakesh K. Jain
The blood vessels of cancerous tumours are leaky1, 2, 3 and poorly organized4, 5, 6, 7. This can increase the interstitial fluid pressure inside tumours and reduce blood supply to them, which impairs drug delivery8, 9. Anti-angiogenic therapies—which ‘normalize’ the abnormal blood vessels in tumours by making them less leaky—have been shown to improve the delivery and effectiveness of chemotherapeutics with low molecular weights10, but it remains unclear whether normalizing tumour vessels can improve the delivery of nanomedicines. Here, we show that repairing the abnormal vessels in mammary tumours, by blocking vascular endothelial growth factor receptor-2, improves the delivery of smaller nanoparticles (diameter, 12 nm) while hindering the delivery of larger nanoparticles (diameter, 125 nm). Using a mathematical model, we show that reducing the sizes of pores in the walls of vessels through normalization decreases the interstitial fluid pressure in tumours, thus allowing small nanoparticles to enter them more rapidly. However, increased steric and hydrodynamic hindrances, also associated with smaller pores, make it more difficult for large nanoparticles to enter tumours. Our results further suggest that smaller (~12 nm) nanomedicines are ideal for cancer therapy due to their superior tumour penetration.
