新加坡UMass 大学：光敏剂加纳米红外颗粒杀死深层恶性肿瘤

　

Tuning light to kill deep cancer tumors

　

　

新加坡UMass医学院开发的纳米粒子为光动力疗法提供了潜在的临床应用

吉姆·Fessenden

马塞诸斯州大学医学院通信

2014年10月15日

　

　

韩刚博士的研究表明，可以将近红外光转化为红光的向上转化纳米颗粒可以用来扩展光动力疗法，治疗一些在深层组织中发现的癌症。

 

由韩刚博士领导的一个国际科学家小组将一种新型纳米颗粒与fda批准的光动力疗法结合在一起，有效地杀死体内深层的癌细胞，对周围组织的损害最小，副作用也比化疗小。这一有希望的新治疗策略可以扩大目前使用的光动力疗法，以进入深层癌症肿瘤。

 

这项研究的第一作者、生物化学与分子药理学助理教授韩博士说:“我们对使用我们的增强型红发射纳米颗粒结合FDA批准的光动力学药物治疗杀死深部肿瘤中的恶性细胞的潜力感到非常兴奋。”“我们已经能够用生物兼容的低功耗、深度组织穿透980纳米近红外光来做到这一点。”

 

在光动力疗法中，也被称为PDT，患者被给予一种无毒的光敏药物，它被身体的所有细胞吸收，包括癌细胞。红色激光特别调谐到药物分子，然后选择性地打开肿瘤区域。当红光与光敏药物相互作用时，它就会产生一种高度反应的氧(单线态氧)，杀死恶性癌细胞，同时使大多数相邻的细胞不受伤害。

　

 

由于红光穿透组织的能力有限，目前的光动力疗法仅用于治疗皮肤癌或非常浅的组织病变。达到更深层次的癌细胞的能力可以扩展光动力疗法的使用。

 

在美国化学学会(American Chemical Society)的《ACS Nano》(ACS Nano)期刊在网上发表的研究中，韩和他的同事描述了一种新的策略，利用一种新型的可转化纳米颗粒(UCNPs)，这种颗粒的大小相当于十亿分之一米，可以作为一种中继站。这些UCNPs与光动力学药物一起使用，并将深穿透的近红外光转化为可见光，这是光动力学治疗中需要的，以激活抗癌药物。

 

为了实现这种光的转换，Han和他的同事设计了一种UCNP，通过在纳米颗粒上涂上氟化钙，并在纳米颗粒上添加镱，从而在光谱的红色部分产生更好的排放。

 

在他们的实验中，研究人员使用了低成本的经FDA批准的光敏剂氨基乙酰丙酸，并将其与他们开发的增强红发射的UCNPs结合。然后，近红外光打开肿瘤位置。Han和他的同事证明，UCNPs成功地将近红外光转化为红光，并在比目前光动力疗法更深层地激活了光动力药物。在体外和动物模型中进行的联合治疗显示，使用较低的激光功率可以改善肿瘤的破坏。

　

 

张勇博士, 领导可转化颗粒开发和应用的新加坡国立大学教授-并没有参与这项研究, 说成功的使这些纳米颗粒增加发射红光，研究小组使用FDA批准的药物创造了最深光动力治疗。

 

张博士说:“这种疗法作为一种非侵入性的杀手，在深度乳腺癌、肺癌和结肠癌超过1厘米的恶性肿瘤上很有前途，而且没有化疗的副作用。”

 

韩说:“这种方法是一种令人兴奋的癌症治疗新进展，既有效又无毒，它也为在其他光子和双光子应用中使用扩增红发射纳米颗粒开辟了新的机会。”

　

 

Tuning light to kill deep cancer tumors

Nanoparticles developed at UMass Medical School advance potential clinical application for photodynamic therapy

 

By Jim Fessenden

UMass Medical School Communications

October 15, 2014

      Research by Gang Han, PhD, shows that upconversion nanoparticles that can convert near-infrared light into red light can be used to extend photodynamic therapy for some cancers found in deeper tissues.

      Research by Gang Han, PhD, shows that upconversion nanoparticles that can convert near-infrared light into red light can be used to extend photodynamic therapy for some cancers found in deeper tissues.

An international group of scientists led by Gang Han, PhD, has combined a new type of nanoparticle with an FDA-approved photodynamic therapy to effectively kill deep-set cancer cells in vivo with minimal damage to surrounding tissue and fewer side effects than chemotherapy. This promising new treatment strategy could expand the current use of photodynamic therapies to access deep-set cancer tumors.

 

“We are very excited at the potential for clinical practice using our enhanced red-emission nanoparticles combined with FDA-approved photodynamic drug therapy to kill malignant cells in deeper tumors,” said Dr. Han, lead author of the study and assistant professor of biochemistry & molecular pharmacology. “We have been able to do this with biocompatible low-power, deep-tissue-penetrating 980-nm near-infrared light.”

 

In photodynamic therapy, also known as PDT, the patient is given a non-toxic light-sensitive drug, which is absorbed by all the body’s cells, including the cancerous ones. Red laser lights specifically tuned to the drug molecules are then selectively turned on the tumor area. When the red light interacts with the photosensitive drug, it produces a highly reactive form of oxygen (singlet oxygen) that kills the malignant cancer cells while leaving most neighboring cells unharmed.

 

Because of the limited ability of the red light to penetrate tissue, however, current photodynamic therapies are only used for skin cancer or lesions in very shallow tissue. The ability to reach deeper set cancer cells could extend the use of photodynamic therapies.

 

In research published online by the journal ACS Nano of the American Chemical Society, Han and colleagues describe a novel strategy that makes use of a new class of upconverting nanoparticles (UCNPs), a billionth of a meter in size, which can act as a kind of relay station. These UCNPs are administered along with the photodynamic drug and convert deep penetrating near-infrared light into the visible red light that is needed in photodynamic therapies to activate the cancer-killing drug.

 

To achieve this light conversion, Han and colleagues engineered a UCNP to have better emissions in the red part of the spectrum by coating the nanoparticles with calcium fluoride and increasing the doping of the nanoparticles with ytterbium.

 

In their experiments, the researchers used the low-cost, FDA-approved photosensitizer drug aminolevulinic acid and combined it with the augmented red-emission UCNPs they had developed. Near-infrared light was then turned on the tumor location. Han and colleagues showed that the UCNPs successfully converted the near-infrared light into red light and activated the photodynamic drug at levels deeper than can be currently achieved with photodynamic therapy methods. Performed in both in vitro and with animal models, the combination therapy showed an improved destruction of the cancerous tumor using lower laser power.

 

Yong Zhang, PhD, chair professor of National University of Singapore and a leader in the development and application of upconversion nanoparticles, who was not involved in the study, said that by successfully engineering amplified red emissions in these nanoparticles, the research team has created the deepest-ever photodynamic therapy using an FDA-approved drug.

 

“This therapy has great promise as a noninvasive killer for malignant tumors that are beyond 1 cm in depth—breast cancer, lung cancer and colon cancer, for example—without the side-effects of chemotherapy,” Dr. Zhang said.

 

Han said, “This approach is an exciting new development for cancer treatment that is both effective and nontoxic, and it also opens up new opportunities for using the augmented red-emission nanoparticles in other photonic and biophotonic applications.”

 

https://umassmed.edu/news/news-archives/2014/10/tuning-light-to-kill-deep-cancer-tumors/