Kumar Rajiv, Belz Jodi, Markovic Stacey, Jadhav Tej, Fowle William, Niedre Mark, Cormack Robert, Makrigiorgos Mike G, Sridhar Srinivas
Nanomedicine Science and Technology Center, Northeastern University, Boston, Massachusetts; Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
Nanomedicine Science and Technology Center, Northeastern University, Boston, Massachusetts.
Int J Radiat Oncol Biol Phys. 2015 Feb 1;91(2):393-400. doi: 10.1016/j.ijrobp.2014.10.041.
In radiation therapy (RT), brachytherapy-inert source spacers are commonly used in clinical practice to achieve high spatial accuracy. These implanted devices are critical technical components of precise radiation delivery but provide no direct therapeutic benefits.
Here we have fabricated implantable nanoplatforms or chemoradiation therapy (INCeRT) spacers loaded with silica nanoparticles (SNPs) conjugated containing a drug, to act as a slow-release drug depot for simultaneous localized chemoradiation therapy. The spacers are made of poly(lactic-co-glycolic) acid (PLGA) as matrix and are physically identical in size to the commercially available brachytherapy spacers (5 mm × 0.8 mm). The silica nanoparticles, 250 nm in diameter, were conjugated with near infrared fluorophore Cy7.5 as a model drug, and the INCeRT spacers were characterized in terms of size, morphology, and composition using different instrumentation techniques. The spacers were further doped with an anticancer drug, docetaxel. We evaluated the in vivo stability, biocompatibility, and biodegradation of these spacers in live mouse tissues.
The electron microscopy studies showed that nanoparticles were distributed throughout the spacers. These INCeRT spacers remained stable and can be tracked by the use of optical fluorescence. In vivo optical imaging studies showed a slow diffusion of nanoparticles from the spacer to the adjacent tissue in contrast to the control Cy7.5-PLGA spacer, which showed rapid disintegration in a few days with a burst release of Cy7.5. The docetaxel spacers showed suppression of tumor growth in contrast to control mice over 16 days.
The imaging with the Cy7.5 spacer and therapeutic efficacy with docetaxel spacers supports the hypothesis that INCeRT spacers can be used for delivering the drugs in a slow, sustained manner in conjunction with brachytherapy, in contrast to the rapid clearance of the drugs when administered systemically. The results demonstrate that these spacers with tailored release profiles have potential in improving the combined therapeutic efficacy of chemoradiation therapy.
在放射治疗（RT）中，近距离放射治疗惰性源间隔器在临床实践中常用于实现高空间精度。这些植入装置是精确放射治疗的关键技术组件，但不提供直接的治疗益处。
在此，我们制备了负载有偶联药物的二氧化硅纳米颗粒（SNP）的可植入纳米平台或放化疗（INCeRT）间隔器，用作同时进行局部放化疗的缓释药物库。间隔器以聚乳酸-羟基乙酸共聚物（PLGA）为基质制成，尺寸与市售近距离放射治疗间隔器（5毫米×0.8毫米）相同。直径为250纳米的二氧化硅纳米颗粒与近红外荧光团Cy7.5偶联作为模型药物，使用不同的仪器技术对INCeRT间隔器的尺寸、形态和组成进行了表征。间隔器进一步掺杂了抗癌药物多西他赛。我们评估了这些间隔器在活小鼠组织中的体内稳定性、生物相容性和生物降解性。
电子显微镜研究表明纳米颗粒分布在整个间隔器中。这些INCeRT间隔器保持稳定，可通过光学荧光进行追踪。体内光学成像研究表明，与对照Cy7.5-PLGA间隔器相比，纳米颗粒从间隔器向相邻组织的扩散缓慢，对照Cy7.5-PLGA间隔器在几天内迅速崩解，Cy7.5爆发性释放。与对照小鼠相比，多西他赛间隔器在16天内显示出肿瘤生长受到抑制。
Cy7.5间隔器的成像和多西他赛间隔器的治疗效果支持了这样的假设，即与全身给药时药物的快速清除相比，INCeRT间隔器可与近距离放射治疗联合以缓慢、持续的方式递送药物。结果表明，这些具有定制释放曲线的间隔器在提高放化疗联合治疗效果方面具有潜力。
