Department of Radiology, LUMC, The Netherlands.
Department of Biochemistry and Molecular Biology, University of Barcelona, Diagonal 643, 08028 Barcelona, Spain.
Biomaterials. 2016 Mar;83:308-20. doi: 10.1016/j.biomaterials.2016.01.006. Epub 2016 Jan 9.
Despite the significant increase in our knowledge on cancer initiation and progression, and the development of novel cancer treatments, overall patient survival rates have thus far only marginally improved. However, it can be expected that lasting tumor control will be attainable for an increasing number of cancer patients in the foreseeable future, which is likely to be achieved by combining cancer chemotherapy with anticancer immunotherapy. A plethora of new cancer chemotherapy reagents are expected to become accessible to the clinic in the coming years which can then be used for efficient tumor debulking and aid in antigen exposure to the immune system. Durable remission and the eradication of micrometastases are likely to be achieved with specialized monoclonal antibodies and therapeutic cancer vaccines that modulate the immune system to overcome immunosuppression and kill distant cancer cells. Moreover, the method of drug delivery to tumors, stromal and immune cells is expected to shift largely from conventional 'free' drug molecules to encapsulated in targeted nano-vehicles, therapeutics often referred to or considered part of "nanomedicine". Several biocompatible nano-vehicles, such as metal-nanoparticles, biodegradable-nanoparticles, liposomes or dendrimers are potential candidates for targeted drug delivery but may also serve additional purposes. A dexterous combination of nanomedicine, cancer immunotherapy and chemotherapeutic engineering are likely to become the basis for new hope in the form of targeted cancer therapies that could attack tumors early in their development. One can envision nano-vehicles that would selectively deliver effective doses of chemotherapeutic agents to cancer cells while leaving healthy cells untouched. Furthermore, given that after chemotherapeutic treatment there often remains a limited number of chemo-resistant tumor cells, which go on to drive tumor progression, nano-vehicles could also be engineered to provoke an appropriate immune response to destroy these cells. Here, we discuss the potential of the combinatorial role of cancer chemotherapy, cancer immunotherapy and the prospective of nanotechnology for the targeted delivery of chemoimmunotherapeutic agents.
尽管我们对癌症的发生和发展有了更深入的了解,并且开发了新的癌症治疗方法,但迄今为止,患者的总体生存率仅略有提高。然而,可以预计,在可预见的未来,越来越多的癌症患者将能够实现持久的肿瘤控制,这可能通过将癌症化疗与癌症免疫治疗相结合来实现。预计在未来几年内将有大量新的癌症化疗试剂进入临床应用,这些试剂可用于有效地肿瘤减瘤,并有助于将抗原暴露于免疫系统。通过专门的单克隆抗体和治疗性癌症疫苗,可以调节免疫系统以克服免疫抑制并杀死远处的癌细胞,从而实现持久的缓解和消除微转移。此外,向肿瘤、基质和免疫细胞输送药物的方法预计将从传统的“游离”药物分子向靶向纳米载体的封装转变,这些治疗剂通常被称为或被认为是“纳米医学”的一部分。几种生物相容性纳米载体,如金属纳米颗粒、可生物降解的纳米颗粒、脂质体或树枝状聚合物,是靶向药物递送的潜在候选物,但也可能具有其他用途。纳米医学、癌症免疫疗法和化疗工程的灵巧结合,很可能成为靶向癌症疗法的新希望的基础,这种疗法可以在肿瘤早期就对其进行攻击。人们可以设想出纳米载体,它们可以选择性地将有效的化疗药物剂量递送到癌细胞,而不影响健康细胞。此外,鉴于化疗后往往仍有数量有限的化疗耐药肿瘤细胞继续推动肿瘤进展,纳米载体也可以被设计成引发适当的免疫反应来破坏这些细胞。在这里,我们讨论了癌症化疗、癌症免疫疗法和纳米技术的组合作用的潜力,用于靶向递送电化疗药物。
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