纳米粒子可以利用肿瘤的弱点，选择性地攻击癌症

纳米保护有效载荷，直到达到一个肿瘤，其工程内容作为一种有效的药物。 钻研世界非常小，研究人员正在探索可生物降解的纳米粒子可以准确地提供抗癌药物攻击神经母细胞瘤，这通常是致命的儿童癌症。

通过汇集专家在儿童肿瘤与纳米技术的专家，研究人员在费城儿童医院的目标是线程提供有效剂量的癌症杀剂，同时避免健康组织的毒性。球队的新研究表明，这种方法能够抑制肿瘤的生长，显著延长动物的生存。 

“这些纳米粒子可以让我们获得更多的“货真价实”-更大的功效，降低总剂量，说：”加勒特·布罗德，MD，在费城儿童医院的儿科肿瘤学家和专家在神经母细胞瘤（CHOP）。“这些纳米颗粒的设计是为了缓慢地将药物传送给肿瘤，它可以杀死增殖的癌细胞，降低全身循环的毒性。”

布罗德的组与组把纳米技术研究人员米迦勒率领Chorny，博士合作，在一项即将发表在5月1日出版癌症信件。

Chorny，反过来，领导的一个研究被刊登在5月出版生物材料, in collaboration with Brodeur’s group and with Robert Levy, MD, and Ivan Alferiev, PhD, both members with Chorny of a cardiology research group at CHOP。 That paper described how the team engineered the specially formulated nanoparticles。

利用纳米颗粒的肿瘤的脆弱性提供抗癌剂

This approach, explained Brodeur, exploits one vulnerability of tumors — called the EPR effect, for enhanced permeability and retention。 “Tumor blood vessels are more leaky and disorganized than blood vessels in normal tissue。 In healthy tissue there are tight junctions in blood vessels,” he said。 “But tumors don’t have those tight junctions and have inefficient circulation, so the nanoparticles we deliver bypass healthy tissues, but accumulate in tumors where they release the anticancer agents。”

Neuroblastoma is a solid tumor of the peripheral nervous system, often appearing in a child’s abdomen or chest。 The most common cancer in infants, neuroblastoma accounts for a disproportionate share of cancer deaths in children, with cure rates lagging behind those for most other pediatric cancers。

“In pediatric oncology, we have largely relied on drugs developed 30 to 40 years ago,” said Brodeur。 “While these have greatly improved overall cure rates over that period from 20 percent to 80 percent, we still need better drugs and more targeted approaches for the most stubborn childhood cancers, including high-risk forms of neuroblastoma。’

Brodeur, Chorny and colleagues used their nanoparticle formulations to deliver a precursor of SN38, the active form of irinotecan, a conventional anticancer drug used for the past 20 years against relapsed neuroblastoma。 In laboratory mice, the study team compared results obtained with the nanoparticle-encapsulated SN38 to those using a comparable dose of irinotecan。

The injected nanoparticles delivered SN38 to the tumor in amounts 100-fold higher than irinotecan, with sustained drug presence over at least 72 hours, and no evidence of toxicity in the mice。 In addition, most of the mice survived tumor-free for over six months after nanoparticle delivery, whereas all the mice treated with irinotecan had tumor recurrence shortly after treatment stopped, and they all died shortly after。

The nanoparticles in the study are ultra small, less than 100 nanometers in diameter (a nanometer is one-millionth of a millimeter, much tinier than red blood cells)。 “We carefully adjust the size of the nanoparticles to find a ‘sweet spot’: small enough to penetrate a tumor, and large enough to carry a therapeutic payload,” said Chorny。 “We can also adjust their composition to keep the active molecule entrapped in a polymer until nanoparticles reach the targeted tumor, and customize the timing of the polymer’s breakdown to allow controlled release of SN38 over a time scale that provides the best therapeutic effects。”

靶向给药四分之一臂靶向癌症治疗

Brodeur aims to translate these preclinical results to human trials within the next year。 “We envision targeted delivery via nanoparticles as a fourth arm of targeted cancer therapy,” he said。 Brodeur added that if nanoparticle delivery proves its worth in clinical trials, it may join three other molecularly-targeted innovations in pediatric cancer treatment already available at CHOP: immunotherapy using bioengineered T cells, radioactive isotopes that preferentially bind to cancer cells, and kinase inhibitors that interrupt abnormal signaling triggered by cancer-driving mutations。

Some nanoparticles are already being used to treat adult cancers, but if the current technique achieves clinical success in neuroblastoma, it would markedly strengthen the arsenal of approaches currently available for treating a childhood cancer。 It holds the potential for broader applications, as well, to deliver other drugs and to treat other cancers currently treated with irinotecan, and perhaps even those that are currently considered resistant to this drug。

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