PDF(Pubmed)
Abstract：
Current therapies for treating Glioblastoma (GB), and brain tumours in general, are inefficient and represent numerous challenges. In addition to surgical resection, chemotherapy and radiotherapy are presently used as standards of care. However, treated patients still face a dismal prognosis with a median survival below 15-18 months. Temozolomide (TMZ) is the main chemotherapeutic agent administered; however, intrinsic or acquired resistance to TMZ contributes to the limited efficacy of this drug. To circumvent the current drawbacks in GB treatment, a large number of classical and non-classical platinum complexes have been prepared and tested for anticancer activity, especially platinum (IV)-based prodrugs. Platinum complexes, used as alkylating agents in the anticancer chemotherapy of some malignancies, are though often associated with severe systemic toxicity (i.e., neurotoxicity), especially after long-term treatments. The objective of the current developments is to produce novel nanoformulations with improved lipophilicity and passive diffusion, promoting intracellular accumulation, while reducing toxicity and optimizing the concomitant treatment of chemo-/radiotherapy. Moreover, the blood-brain barrier (BBB) prevents the access of the drugs to the brain and accumulation in tumour cells, so it represents a key challenge for GB management. The development of novel nanomedicines with the ability to (i) encapsulate Pt-based drugs and pro-drugs, (ii) cross the BBB, and (iii) specifically target cancer cells represents a promising approach to increase the therapeutic effect of the anticancer drugs and reduce undesired side effects. In this review, a critical discussion is presented concerning different families of nanoparticles able to encapsulate platinum anticancer drugs and their application for GB treatment, emphasizing their potential for increasing the effectiveness of platinum-based drugs.
摘要：
目前治疗胶质母细胞瘤的疗法（GB），和一般的脑肿瘤，效率低下，代表着众多挑战。除了手术切除,化疗和放疗目前被用作护理标准。然而,接受治疗的患者仍面临不良预后,中位生存期低于15-18个月.替莫唑胺（TMZ）是主要的化疗药物；然而，对TMZ的内在或获得性耐药性导致该药物的疗效有限。为了规避目前GB治疗中的弊端，已经制备了大量经典和非经典铂配合物，并进行了抗癌活性测试，尤其是以铂(IV)为基础的前药。铂配合物,在一些恶性肿瘤的抗癌化疗中用作烷化剂，尽管通常与严重的全身毒性有关(即，神经毒性)，尤其是长期治疗后。当前发展的目标是生产具有改善的亲脂性和被动扩散的新型纳米制剂，促进细胞内积累，同时降低毒性并优化化学/放射疗法的伴随治疗。此外，血脑屏障（BBB）阻止药物进入大脑并在肿瘤细胞中积累，因此，它代表了GB管理的关键挑战。新型纳米药物的开发，能够（i）封装基于Pt的药物和前药，(ii)穿过BBB，和(iii)特异性靶向癌细胞代表了增加抗癌药物的治疗效果和减少不期望的副作用的有希望的方法。在这次审查中,提出了关于能够封装铂抗癌药物的不同纳米颗粒家族及其在GB治疗中的应用的重要讨论，强调它们提高铂类药物有效性的潜力。
