Targeting Accessories to the Crime: Nanoparticle Nucleic Acid Delivery to the Tumor Microenvironment.
Targeting Accessories to the Crime: Nanoparticle Nucleic Acid Delivery to the Tumor Microenvironment.
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DOI：
10.3389/fphar.2018.00307
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发表时间：
2018
影响因子：
5.6
通讯作者：
Pecot CV
中科院分区：
文献类型：
--
作者：
Harrison EB;Azam SH;Pecot CV
癌症的核酸递送具有非凡的前景。在癌细胞中增加肿瘤抑制基因的表达或抑制癌基因具有重要的治疗潜力。然而，一些障碍阻碍了癌症基因递送的进展。这些障碍包括向癌细胞和相关的细胞内区室的有效递送。尽管病毒基因递送可能是有效的，但它具有免疫刺激性、潜在致突变性以及缺乏时间控制的缺点。已经开发了各种纳米颗粒（NP）平台来克服核酸递送的障碍，但仍然存在一些挑战。其中一个挑战是纳米颗粒在肿瘤微环境（TME）内的非癌细胞以及循环系统中的积聚。虽然在某些情况下，这些与癌症相关细胞的摄取被认为是一种脱靶效应，但现在已经出现了一些利用纳米颗粒介导的基因递送来有意改变肿瘤微环境的策略。例如，纳米颗粒在形状和大小上与病原体的相似性促进了抗原呈递细胞的摄取，这可用于增强免疫刺激并促进T淋巴细胞对肿瘤的杀伤。在免疫治疗时代，提高免疫系统消除癌细胞的能力已被证明是癌症纳米技术中一个令人兴奋的新领域。鉴于与癌症相关的细胞在肿瘤生长和转移中的重要性，在肿瘤微环境中靶向这些细胞为纳米颗粒开辟了新的治疗应用。这篇综述将涵盖纳米颗粒在动物模型和患者中非癌细胞积聚的证据，总结促进纳米颗粒向不同细胞类型递送的特征，并描述肿瘤微环境内基因修饰的几种治疗策略。
Nucleic acid delivery for cancer holds extraordinary promise. Increasing expression of tumor suppressor genes or inhibition of oncogenes in cancer cells has important therapeutic potential. However, several barriers impair progress in cancer gene delivery. These include effective delivery to cancer cells and relevant intracellular compartments. Although viral gene delivery can be effective, it has the disadvantages of being immuno-stimulatory, potentially mutagenic and lacking temporal control. Various nanoparticle (NP) platforms have been developed to overcome nucleic acid delivery hurdles, but several challenges still exist. One such challenge has been the accumulation of NPs in non-cancer cells within the tumor microenvironment (TME) as well as the circulation. While uptake by these cancer-associated cells is considered to be an off-target effect in some contexts, several strategies have now emerged to utilize NP-mediated gene delivery to intentionally alter the TME. For example, the similarity of NPs in shape and size to pathogens promotes uptake by antigen presenting cells, which can be used to increase immune stimulation and promote tumor killing by T-lymphocytes. In the era of immunotherapy, boosting the ability of the immune system to eliminate cancer cells has proven to be an exciting new area in cancer nanotechnology. Given the importance of cancer-associated cells in tumor growth and metastasis, targeting these cells in the TME opens up new therapeutic applications for NPs. This review will cover evidence for non-cancer cell accumulation of NPs in animal models and patients, summarize characteristics that promote NP delivery to different cell types, and describe several therapeutic strategies for gene modification within the TME.
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影响因子：
64.5
作者：
Cubillos-Ruiz JR;Silberman PC;Rutkowski MR;Chopra S;Perales-Puchalt A;Song M;Zhang S;Bettigole SE;Gupta D;Holcomb K;Ellenson LH;Caputo T;Lee AH;Conejo-Garcia JR;Glimcher LH
通讯作者：
Glimcher LH
使用miRNA Mimetics在体内重新编程与肿瘤相关的树突状细胞触发了针对卵巢癌的保护性免疫。
影响因子：
11.2
作者：
Cubillos-Ruiz JR;Baird JR;Tesone AJ;Rutkowski MR;Scarlett UK;Camposeco-Jacobs AL;Anadon-Arnillas J;Harwood NM;Korc M;Fiering SN;Sempere LF;Conejo-Garcia JR
通讯作者：
Conejo-Garcia JR
影响因子：
3.4
作者：
Beg MS;Brenner AJ;Sachdev J;Borad M;Kang YK;Stoudemire J;Smith S;Bader AG;Kim S;Hong DS
通讯作者：
Hong DS
影响因子：
17.1
作者：
Dhodapkar MV;Sznol M;Zhao B;Wang D;Carvajal RD;Keohan ML;Chuang E;Sanborn RE;Lutzky J;Powderly J;Kluger H;Tejwani S;Green J;Ramakrishna V;Crocker A;Vitale L;Yellin M;Davis T;Keler T
通讯作者：
Keler T
影响因子：
5.1
作者：
Anwer, K.;Barnes, M. N.;Alvarez, R. D.
通讯作者：
Alvarez, R. D.