Nanoparticulate drug delivery systems composed of amphiphilic block and hyperbranched copolymers

将纳米技术应用于药物，称为“纳米药物”，具有技术和概念突破的巨大潜力。纳米级药物输送系统的发展最终将使我们能够靶向选定的体内细胞或组织，并控制药物在该部位的释放，从而提高给药的安全性和有效性。该提案的总体目标是开发新的肿瘤定向纳米颗粒，用于化疗药物或热杀伤细胞的局部治疗。我们最初的重点将是合成、制备和表征由组织相容性聚合物制成的纳米颗粒，并装载抗癌药物紫杉醇和顺铂，用于膀胱癌的潜在应用。大多数患有这种癌症的患者都是浅表疾病，只影响膀胱壁的表面衬里。目前使用药物直接输注膀胱的化疗方法不是很有效，因为药物与膀胱壁的接触时间只有2小时左右，就会发生排尿。我们认为，用组织粘附基团修饰药物纳米颗粒的表面可以延长接触时间，增加药物进入组织的吸收，提高有效性，并可能减少不必要的副作用。我们已经组建了一个杰出的合作团队，他们将开发，例如，可以共同递送两种药物的纳米粒子，以及可以用特定波长的光照射并加热并杀死癌细胞的带有金涂层的纳米粒子。

The application of nanotechnology to drugs, referred to as "nanomedicines" has a high potential for technological and conceptual breakthroughs. The development of nano-sized drug delivery systems will ultimately allow us to target selected cells or tissues within the body and control the release of drug at that site, resulting in greater safety and effectiveness of the administered drug. The overall goal of this proposal is to develop novel, tumor site-directed nanoparticles for the local treatment of disease with either chemotherapeutic agents or cell-killing by heat. Our initial focus will be the synthesis, preparation and characterization of nanoparticles made of tissue-compatible polymers and loaded with the anticancer drugs, paclitaxel and cisplatin, for potential application in bladder cancer. Most patients with this cancer have superficial disease, affecting just the surface lining of the bladder wall. Current chemotherapy treatments using drugs instilled directly into the bladder are not very effective because the contact time of the drug with the bladder wall is only about 2 hours, before voiding occurs. We believe that modifying the surfaces of the drug nanoparticles with tissue-adhering groups should prolong the contact time, increase uptake of drug into the tissue, increase effectiveness and potentially decrease unwanted side effects. We have assembled an outstanding team of collaborators who will develop, for example, nanoparticles that can co-deliver two drugs and nanoparticles with a gold coating that can be irradiated with light of a certain wavelength and will heat up and kill cancer cells.