-
靶向治疗的基本原理是阻断特定的生物信号传导通路或定向破坏参与肿瘤生长或促进肿瘤进展的癌蛋白[1]。靶向治疗除了可以通过单克隆抗体(monoclonal antibody,MAb)或小分子抑制剂改变特定细胞信号的直接方法来实现外,亦可通过间接方法(如利用细胞毒性药物靶向在肿瘤细胞中过表达或仅表达于肿瘤细胞的分子靶标)来实现。细胞毒性药物可通过纳米载药体系递送,该递送方法更特异和高效,可使靶向治疗克服传统化疗和生物治疗缺乏特异性的缺点[1]。
树状大分子呈大小均匀的球形结构,其内部核心成分稳定,可提供动态内腔,外表面具有可供修饰的基团,且具有易于穿过细胞膜的能力,这些特点均有利于其作为载药体系的核心结构[2-3]。近年来,针对基于树状大分子材料构建的纳米载药体系的研究较多,主要研究方向为采用不同的靶向基团对载药体系进行修饰、装载不同的治疗剂进行治疗、装载不同的放射性核素进行特异性显像和靶向治疗,这些研究使基于树状大分子材料构建的纳米载药体系的功能受到广泛关注。
基于树状大分子材料构建的纳米载药体系用于肿瘤靶向治疗的研究进展
Research progress of nano-drug delivery systems based on dendrimer materials for tumor targeted therapy
-
摘要: 近年来兴起的树状大分子材料的结构可控,且其与细胞膜和各种活性药物分子具有独特的相互作用,因此成为构建纳米载药体系的优良材料,并在肿瘤靶向治疗领域得到了广泛研究。树状大分子作为具有良好生物相容性的纳米分子,可与肿瘤靶向分子偶联,从而将活性药物分子特异性递送到肿瘤组织,如此可最大限度地提高药物的靶向性,并减少其对非靶组织的毒性作用。笔者就近年来基于树状大分子材料构建的纳米载药体系用于肿瘤靶向治疗的研究进展进行综述。Abstract: Dendrimer materials emerging in recent years have become excellent materials for constructing nano-drug delivery systems due to their controllable structures and unique interactions with cell membranes and various active drug molecules, and have been widely studied in the field of tumor targeted therapy. As nanomolecules with good biocompatibility, dendrimers can be conjugated to tumor-targeting molecules to specifically deliver active drug molecules to tumor tissues, which can maximize drug targeting and reduce toxic effects on non-target tissues. In this paper, the recently research progress of nano-drug delivery systems based on dendrimer materials for tumor targeted therapy is reviewed.
-
Key words:
- Dendrimers /
- Nanocomposites /
- Radioisotopes /
- Drug delivery systems /
- Targeted therapy
-
[1] Pérez-Herrero E, Fernández-Medarde A. Advanced targeted therapies in cancer: drug nanocarriers, the future of chemotherapy[J]. Eur J Pharm Biopharm, 2015, 93: 52−79. DOI: 10.1016/j.ejpb.2015.03.018. [2] Chauhan AS. Dendrimers for drug delivery[J/OL]. Molecules, 2018, 23(4): 938[2021-06-12]. https://www.mdpi.com/1420-3049/23/4/938. DOI: 10.3390/molecules23040938. [3] Ghaffari M, Dehghan G, Abedi-Gaballu F, et al. Surface functionalized dendrimers as controlled-release delivery nanosystems for tumor targeting[J]. Eur J Pharm Sci, 2018, 122: 311−330. DOI: 10.1016/j.ejps.2018.07.020. [4] Mittal P, Saharan A, Verma R, et al. Dendrimers: a new race of pharmaceutical nanocarriers[J/OL]. Biomed Res Int, 2021, 2021: 8844030[2021-06-12]. https://www.hindawi.com/journals/bmri/20>21/8844030. DOI: 10.1155/2021/8844030. [5] Palmerston Mendes L, Pan JY, Torchilin VP. Dendrimers as nanocarriers for nucleic acid and drug delivery in cancer therapy[J/OL]. Molecules, 2017, 22(9): 1401[2021-06-12]. https://www.mdpi.com/1420-3049/22/9/1401. DOI: 10.3390/molecules22091401. [6] Duncan R, Izzo L. Dendrimer biocompatibility and toxicity[J]. Adv Drug Deliv Rev, 2005, 57(15): 2215−2237. DOI: 10.1016/j.addr.2005.09.019. [7] Dias AP, Da Silva Santos S, Da Silva JV, et al. Dendrimers in the context of nanomedicine[J]. Int J Pharm, 2020, 573: 118814. DOI: 10.1016/j.ijpharm.2019.118814. [8] Sherje AP, Jadhav M, Dravyakar BR, et al. Dendrimers: a versatile nanocarrier for drug delivery and targeting[J]. Int J Pharm, 2018, 548(1): 707−720. DOI: 10.1016/j.ijpharm.2018.07.030. [9] Chis AA, Dobrea C, Morgovan C, et al. Applications and limitations of dendrimers in biomedicine[J/OL]. Molecules, 2020, 25(17): 3982[2021-06-12]. https://www.mdpi.com/1420-3049/25/17/3982. DOI: 10.3390/molecules25173982. [10] Vu MT, Bach LG, Nguyen DC, et al. Modified carboxyl-terminated PAMAM dendrimers as great cytocompatible nano-based drug delivery system[J/OL]. Int J Mol Sci, 2019, 20(8): 2016[2021-06-12]. https://www.mdpi.com/1422-0067/20/8/2016. DOI: 10.3390/ijms20082016. [11] Wang H, Chang H, Zhang Q, et al. Fabrication of low-generation dendrimers into nanostructures for efficient and nontoxic gene delivery[J]. Top Curr Chem (Cham), 2017, 375(3): 62. DOI: 10.1007/s41061-017-0151-6. [12] Chanphai P, Tajmir-Riahi HA. Characterization of folic acid-PAMAM conjugates: drug loading efficacy and dendrimer morphology[J]. J Biomol Struct Dyn, 2018, 36(7): 1918−1924. DOI: 10.1080/07391102.2017.1341339. [13] Thanh VM, Nguyen TH, Tran TV, et al. Low systemic toxicity nanocarriers fabricated from heparin-mPEG and PAMAM dendrimers for controlled drug release[J]. Mater Sci Eng C Mater Biol Appl, 2018, 82: 291−298. DOI: 10.1016/j.msec.2017.07.051. [14] Castro RI, Forero-Doria O, Guzmán L. Perspectives of dendrimer-based nanoparticles in cancer therapy[J]. An Acad Bras Cienc, 2018, 90(2 Suppl 1): S2331−2346. DOI: 10.1590/0001-3765201820170387. [15] 冯成涛, 张海波, 郑皓等. 131I-PAMAM(G5.0)介导靶向肽在甲状腺髓样癌模型中的实验研究[J]. 国际放射医学核医学杂志, 2019, 43(6): 528−537. DOI: 10.3760/cma.j.issn.1673−4114.2019.06.007.
Feng CT, Zhang HB, Zheng H, et al. Efficiacy of 131I-generation 5.0 polyamidamine-mediated targeting peptide in the mice with medullary thyroid carcinoma[J]. Int J Radiat Med Nucl Med, 2019, 43(6): 528−537. DOI: 10.3760/cma.j.issn.1673−4114.2019.06.007.[16] Tekade RK, Dutta T, Tyagi A, et al. Surface-engineered dendrimers for dual drug delivery: a receptor up-regulation and enhanced cancer targeting strategy[J]. J Drug Target, 2008, 16(10): 758−772. DOI: 10.1080/10611860802473154. [17] Qi R, Majoros I, Misra AC, et al. Folate receptor-targeted dendrimer-methotrexate conjugate for inflammatory arthritis[J]. J Biomed Nanotechnol, 2015, 11(8): 1431−1441. DOI: 10.1166/jbn.2015.2077. [18] Kesharwani P, Tekade RK, Jain NK. Generation dependent safety and efficacy of folic acid conjugated dendrimer based anticancer drug formulations[J]. Pharm Res, 2015, 32(4): 1438−1450. DOI: 10.1007/s11095-014-1549-2. [19] Zhu JY, Shi XY. Dendrimer-based nanodevices for targeted drug delivery applications[J]. J Mater Chem B, 2013, 1(34): 4199−4211. DOI: 10.1039/c3tb20724b. [20] Mehra NK, Mishra V, Jain NK. Receptor-based targeting of therapeutics[J]. Ther Deliv, 2013, 4(3): 369−394. DOI: 10.4155/tde.13.6. [21] Anbazhagan R, Muthusamy G, Krishnamoorthi R, et al. PAMAM G4.5 dendrimers for targeted delivery of ferulic acid and paclitaxel to overcome P-glycoprotein-mediated multidrug resistance[J]. Biotechnol Bioeng, 2021, 118(3): 1213−1223. DOI: 10.1002/bit.27645. [22] Jain NK, Tare MS, Mishra V, et al. The development, characterization and in vivo anti-ovarian cancer activity of poly(propylene imine) (PPI)-antibody conjugates containing encapsulated paclitaxel[J]. Nanomedicine, 2015, 11(1): 207−218. DOI: 10.1016/j.nano.2014.09.006. [23] Marcinkowska M, Stanczyk M, Janaszewska A, et al. Multicomponent conjugates of anticancer drugs and monoclonal antibody with PAMAM dendrimers to increase efficacy of HER-2 positive breast cancer therapy[J]. Pharm Res, 2019, 36(11): 154. DOI: 10.1007/s11095-019-2683-7. [24] Yousef S, Alsaab HO, Sau S, et al. Development of asialoglycoprotein receptor directed nanoparticles for selective delivery of curcumin derivative to hepatocellular carcinoma[J/OL]. Heliyon, 2018, 4(12): e01071[2021-06-12]. https://www.sciencedirect.com/science/article/pii/S2405844018339604. DOI: 10.1016/j.heliyon.2018.e01071. [25] Xiao TT, Li D, Shi XY, et al. PAMAM dendrimer-based nanodevices for nuclear medicine applications[J]. Macromol Biosci, 2020, 20(2): e1900282. DOI: 10.1002/mabi.201900282. [26] Jeon J. Review of therapeutic applications of radiolabeled functional nanomaterials[J/OL]. Int J Mol Sci, 2019, 20(9): 2323[2021-06-12]. https://www.mdpi.com/1422-0067/20/9/2323. DOI: 10.3390/ijms20092323. [27] 钟建秋. 131I标记肿瘤靶向复合物RGDyC-PEG-PAMAM的合成过程及其生物活性研究[D]. 广州: 广东药科大学, 2017.
Zhong JQ. Study on the synthesis and bioactivity of 131I-labeled tumor targeting complex RGDyC-PEG-PAMAM[D]. Guangzhou: Guangdong Pharmaceutical University, 2017.[28] Song NN, Zhao LZ, Xu XY, et al. LyP-1-modified multifunctional dendrimers for targeted antitumor and antimetastasis therapy[J]. ACS Appl Mater Interfaces, 2020, 12(11): 12395−12406. DOI: 10.1021/acsami.9b18881. [29] Akbari-Karadeh S, Aghamiri SMR, Tajer-Mohammad-Ghazvini P, et al. Radiolabeling of biogenic magnetic nanoparticles with rhenium-188 as a novel agent for targeted radiotherapy[J]. Appl Biochem Biotechnol, 2020, 190(2): 540−550. DOI: 10.1007/s12010-019-03079-x. [30] Tassano M, Oddone N, Fernández M, et al. Evaluation of chromosomal aberrations induced by 188Re-dendrimer nanosystem on B16f1 melanoma cells[J]. Int J Radiat Biol, 2018, 94(7): 664−670. DOI: 10.1080/09553002.2018.1478161. [31] Dash A, Pillai MRA, Knapp Jr FF. Production of 177Lu for targeted radionuclide therapy: available options[J]. Nucl Med Mol Imaging, 2015, 49(2): 85−107. DOI: 10.1007/s13139-014-0315-z. [32] Mendoza-Nava H, Ferro-Flores G, de María Ramírez F, et al. Fluorescent, plasmonic, and radiotherapeutic properties of the 177Lu–dendrimer-AuNP–folate–bombesin nanoprobe located inside cancer cells[J]. Mol Imaging, 2017, 16: 1536012117704768. DOI: 10.1177/1536012117704768. [33] Jain K, Kesharwani P, Gupta U, et al. Dendrimer toxicity: let's meet the challenge[J]. Int J Pharm, 2010, 394(1/2): 122−142. DOI: 10.1016/j.ijpharm.2010.04.027.
计量
- 文章访问数: 3777
- HTML全文浏览量: 2862
- PDF下载量: 11