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化学进展 2016, Vol. 28 Issue (9): 1397-1405 DOI: 10.7536/PC160423 前一篇   后一篇

• 综述与评论 •

增强纳米药物载体肿瘤内渗透分布的研究进展

韩冬琳1, 亓洪昭1, 赵瑾1, 龙丽霞1, 任玉2, 原续波1*   

  1. 1. 天津大学材料科学与工程学院 天津市材料复合与功能化重点实验室 天津 300072;
    2. 天津医科大学基础医科研究中心 天津 300070
  • 收稿日期:2016-04-01 修回日期:2016-06-01 出版日期:2016-09-15 发布日期:2016-08-16
  • 通讯作者: 原续波 E-mail:xbyuan@tju.edu.cn
  • 基金资助:
    国家自然科学基金项目(No.51303125,51473119)资助

Enhancement of Intra-Tumor Penetration and Distribution of Nano-Drug Carriers

Han Donglin1, Qi Hongzhao1, Zhao Jin1, Long Lixia1, Ren Yu2, Yuan Xubo1*   

  1. 1. Tianjin Key Laboratory of Composite & Functional Materials, School of Materials Science & Engineering, Tianjin University, Tianjin 30007;
    2. Basic Medical Research Center, Tianjin Medical University, Tianjin 300070, China
  • Received:2016-04-01 Revised:2016-06-01 Online:2016-09-15 Published:2016-08-16
  • Supported by:
    The work was supported by the National Natural Science Foundation of China (No. 51303125,51473119).
利用纳米载体负载小分子化疗药物、蛋白和基因有助于降低这些药物的毒副作用,在肿瘤治疗中发挥着重要作用。然而,由于肿瘤独特的病理生理学特点,纳米药物载体在肿瘤中的分布并不均匀,无法有效渗透到肿瘤深部,使药物的疗效受到限制。通过控制纳米药物载体的粒径、表面电位、表面功能基团和形状等理化性质,可以实现其在肿瘤组织中的有效扩散。本文从无机和有机纳米药物载体两个体系出发,综述了通过对纳米药物载体的组成、结构设计和理化性质的调控,促进其在肿瘤组织中均匀分布及深度渗透的研究进展,并展望了面临的挑战和可能的解决途径。
The tumor therapeutics effect of chemotherapeutant, proteins and genes could be improved when they are loaded in nano-drug carriers. But in some cases the therapeutics effects are modest due to the poor penetration and distribution of nano-carriers in the heterogeneous tumor tissue. During the recent years, increasing efforts have been dedicated to improve the intra-tumor penetration by controlling the size, surface zeta potential, targeting agents, and shape of nano-drug carriers. This paper reviews the progress in enhancement of intra-tumor penetration and distribution of nano-drug carriers through the modification of their components, structures and physicochemical properties. The challenges of nano-drug carriers in tumor treatment are raised and the possible solutions are proposed.

Contents
1 Introduction
2 Inorganic nano-drug carriers
2.1 Meso-porous silicon nano-drug carriers
2.2 Gold nano-drug carriers
3 Organic nano-drug carriers
3.1 Micelles
3.2 Dendrimers
3.3 Liposomes
3.4 Polymer nanocapsule
4 Conclusion

中图分类号: 

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[1] Wong C, Stylianopoulos T, Cui J A, Martin J, Chauhan V P, Jiang W, Popovic Z, Jain R K, Bawendi M G, Fukumura D. Proc. Natl. Acad. Sci. U. S. A., 2011, 108:2426.
[2] Chauhan V P, Stylianopoulos T, Martin J D, Popovic Z, Chen O, Kamoun W S, Bawendi M G, Fukumura D, Jain R K. Nature Nanotech., 2012, 7:383.
[3] Dhanikula R S, Argaw A, Bouchard J F, Hildgen P. Mol. Pharm., 2008, 5:105.
[4] Chilkoti A, Dreher M R, Meyer D E, Raucher D. Adv. Drug Deliv. Rev., 2002, 54:613.
[5] Jang S H, Wientjes M G, Lu D, Au L S. Pharm. Res., 2003, 20:1337.
[6] Waite C L, Roth C M. Biotechnology and Bioengineering, 2011, 108:2999.
[7] Andrew I, Minchinton, Tannock L F. Nature Reviews Cancer, 2006, 6:583.
[8] Maeda H, Nakamura H, Fang J. Adv. Drug Deliv. Rev., 2013, 65:71.
[9] Goel S, Duda D G, Xu L, Munn L L, Boucher Y, Fukumura D, Jain R K. Physiol. Rev., 2011, 91:1071.
[10] Kanapathipillai M, Brock A, Ingber D E. Adv. Drug Deliv. Rev., 2014, 79:107.
[11] Jackson D E. FEBs Letters, 2003, 540:7.
[12] Divan A, Lawry J, Dunsmore I R, Parsons A, Royds J A. Cancer Res., 2001, 61:3157.
[13] Trédan O, Galmarini C M, Patel K,Tannock I F. J. Natl. Cancer Inst., 2007, 99:1441.
[14] Kizaka-Kondoh S, Inoue M, Harada H, Hiraoka M. Cancer Science, 2003, 94:1021.
[15] Grantab R, Sivananthan S, Tannock I F. Cancer Res., 2006, 66:1033.
[16] Padera T P, Stoll B R, Tooredman J B, Capen D, Tomaso E D, Jain R K. Nature, 2004, 427:695.
[17] Jain R K. Cancer Res., 1987, 47:3039.
[18] Netti P A, Berk D A, Swartz M A, Grodzinsky A J, Jain R K. Cancer Res., 2000, 60:2497.
[19] Brown E B, Boucher Y, Nasser S, Jain R K. Microvascular Research, 2004, 67:231.
[20] Heldin C H, Rubin K, Pietras K, Ostman A. Nat. Rev. Cancer, 2004, 4:806.
[21] Kwon I K, Lee S C, Han B, Park K. J. Controlled Release, 2012, 164:108.
[22] Cabral H, Matsumoto Y, Mizuno K, Chen Q, Murakami M, Kimura M, Terada Y, Kano M R, Miyazono K, Uesaka M, Nishiyama N, Kataoka K. Nat. Nanotechnol., 2011, 6:815.
[23] Lee H, Hoang B, Fonge H, Reilly R M, Allen C. Pharm. Res., 2010, 27:2343.
[24] Ernsting M J, Foltz W D, Undzys E, Tagami T, Li S D, Biomaterials, 2012, 33:3931.
[25] Tong R T, Boucher Y, Kozin S V, Winkler F, Hicklin D J, Jain R K. Cancer Res., 2004, 64:3731.
[26] Khawar I A, Kim J H, Kuh H J. J. Controlled Release, 2015, 201:78.
[27] Jain R K, Stylianopoulos T. Nat. Rev. Clin. Oncol., 2010, 7:653.
[28] Parodi A, Haddix S G, Taghipour N, Scaria S, Taraballi F, Cevenini A, Yazdi I K, Corbo C, Palomba R, Khaled S Z, Martinez J O, Brown B S, Isenhart L, Tasciotti E. ACS Nano, 2014, 8:9874.
[29] Tang L, Fan T M, Borst L B, Cheng J J. ACS Nano, 2012, 6:3954.
[30] Li H J, Du J Z, Du X J, Xu C F, Sun C Y, Wang H X, Cao Z T, Yang X Z, Zhu Y H, Nie S, Wang J. Proc. Natl. Acad. Sci. U.S.A., 2016, 113:4164.
[31] Tang L, Yang X J, Qian Y, Cai K M, Wang H, Chaudhrgy I, Yao C, Zhou Q, Kwon M, Hartman J A, Dobrucki I T, Borst L B, Lezmi S, Helferich W G, Ferguson A L, Fan T M, Cheng J J. Proc. Natl. Acad. Sci. U. S. A., 2014, 111:15344.
[32] Trewyn B G, Nieweg J A, Zhao Y Y, Lin V S Y. Chem. Eng., 2008, 137:23.
[33] Lu X L, Hargrove D, Tran T H, Salner A. J. Nucl. Med., 2014, 5:210.
[34] Cheng Y, Meyers J D, Broome A M, Kenney M E, Basilion J P, Bruda C. J. Am. Chem. Soc., 2011, 133:2583.
[35] Brown S D, Nativo P, Smith J A, Stirling D, Edwards P R, Venugopal B, Flint D J, Plumb J A, Graham D, Wheate N J. J. Am. Chem. Soc., 2010, 132:4678.
[36] Chithrani D B, Jelveh S, Jalali F, Prooijen M V, Allen C, Bristow R G, Hill R P, Jaffray D A. Radiat. Res., 2010, 173:719.
[37] Yohan D, Chithrani B D. Biomed. Nanotechnol., 2014, 10:2371.
[38] Ruan S, Cao X, Cun X, Hu G L, Zhang Y J, Lu L B, He Q, Gao H L. Biomaterials, 2015, 60:100.
[39] Huo S, Ma H, Huang K. Cancer Res., 2013, 73:319.
[40] Goodman T T, Olive P L, Pun S H. Int. J. Nanomedicine, 2007, 2:265.
[41] Huang K, Ma H, Liu J, Huo S D, Kumart A, Weit T, Zhang X, Jin S, Gan Y L, Wang P C, He S T, Zhang X N, Liang X J. ACS Nano, 2012, 6:4483.
[42] Hainfeld J F, O'Connor M J, Lin P, Qian L P, Slatkin D N, Smiliiowitz H M. PloS One, 2014, 9:e88414.
[43] Nam J, Won N, Jin H, Chung H, Kim S. J. Am. Chem. Soc., 2009, 131:13639.
[44] Jin S, Ma X, Ma H, Zheng K, Liu J, Hou S, Meng J, Wang P C, Wu X C, Liang X J. Nanoscale, 2013, 5:143.
[45] England C G, Priest T, Zhang G D, Sun X H, Patel D N, McNally L R, Berkel V V, Gobin A M, Frieboes H B. Inter. J. Nanomed., 2013, 8:3603.
[46] Black K C L, Wang Y, Luehmann H P, Cai W X, Pang B, Zhao Y F, Cutler C S, Wang L V, Liu Y J, Xia Y N. ACS Nano, 2014, 8:4385.
[47] Doshi N, Prabhakarpandian B, Rea-Ramsey A, Pant K, Sundaram S, Mitragotri S. J. Controlled Release, 2010, 146:196.
[48] Tan J, Shah S, Thomas A, Ou-Yang H D, Liu Y. Microfluid Nanofluid, 2013, 14:77.
[49] . Kersey F, Merkel T J, Perry J, Napier M E, DeSimone J M. Langmuir, 2012, 28:8773.
[50] Venkataraman S, Hedrick J L, Ong Z Y, Yang C, Ee P L R, Hammond P T, Yang Y Y. Adv. Drug Deliv. Rev., 2011, 63:1228.
[51] Doshi N, Mitragotri S. PLoS One, 2010, 5:e10051.
[52] . Zhang K, Fang H, Chen Z, Taylor J S A, Wooley K L. Bioconjugate Chem., 2008, 19:1880.
[53] Kataoka K, Harada A, Nagasaki Y. Adv. Drug Deliv. Rev., 2001, 47:113.
[54] Rong T, Houman D H, Robert L, Kohane D S. J. Am. Chem. Soc., 2012, 134:8848.
[55] Jiang X Y, Xin H L, Gu J J, Xu X M, Xia W Y, Chen S, Xie Y K, Chen L C, Chen Y Z, Sha X Y, Fang S Y. Biomaterials, 2013, 34:1739.
[56] He H, Li Y, Jia X R, Du J, Ying X, Lu W L, Lou J N, Wei Y. Biomaterials, 2011, 32:478.
[57] Sunoqrot S, Bugno J, Lantvit D, Burdette J E, Hong S. J. Controlled Release, 2014, 191:115.
[58] Sunoqrot S, Bae J W, Pearson R M, Shyu K, Liu Y, Kim D H, Hong S. Biomacromolecules, 2012, 13:1223.
[59] Koo L Y, Irvine D J, Mayes A M, Lauffenburger D A, Grifffth L G. J. Cell Sci., 2002, 115:1423.
[60] Liu S. Bioconjugate Chem., 2009, 20:2199.
[61] Wang L, Shi J, Kim Y S, Zhai S, Jia B, Zhao H, Liu Z, Wang F, Chen X, Liu S. Mol. Pharm., 2006, 6:231.
[62] Allen T M, Cullis P R. Adv. Drug Deliv. Rev., 2013, 65:36.
[63] Deamer D W. The FASEB Journal, 2014, 24:1308.
[64] Ewer M S, Martin F J, Henderson C, Shapiro C L, Benjamin R S, Gabizon A A. Oncol., 2004, 31:161.
[65] Maruyama K. Adv. Drug Deliv. Rev., 2011, 63:161.
[66] Zhu L, Kate P, Torchilin V P. ACS Nano, 2012, 6:3491.
[67] Thurston G, Mclean J W, Baluk P, Haskell A, Murphy T J, Hanahan D, McDonald D M. J. Clin. Invest., 1998, 101:1401.
[68] Krasnici S, Werner A, Eichhorn M E, Schmitt-Sody M, Pahemik S A, Sauer B, Schulze B, Teifel M, Michaelis Uwe, Naujoks K, Dellian M. Int. J. Cancer, 2003, 105:561.
[69] Kano M R, Bae Y, Morishita Y, Yashiro M, Oka M, Fujii T, Komuro A, Kiyono K, Kaminishi M, Hirakawa K, Ouchi Y, Nishiyama N, Kataoka K, Miyazono K. Proc. Natl. Acad. Sci. U. S. A., 2007, 104:3460.
[70] Yan M, Liang M, Wen J, Liu Y, Lu Y F, Chen I S Y. J. Am. Chem. Soc., 2012, 134:13542.
[71] Yan M, Du J, Gu Z, Liang M, Hu Y F, Zhang W J, Priceman S, Wu L L, Zhou H, Liu Z, Segura T, Tang Y, Lu Y F. Nature Nanotech., 2010, 5:48.
[72] Liu C Y, Wen J, Meng Y B, Zhang K L, Zhu J L, Ren Y, Qian X M, Yuan X B, Lu Y F, Kang C S. Adv. Mater., 27:292.
[73] Du J, Jin J, Yan M, Lu Y. Curr. Drug MeTab., 2012, 13:82.
[74] Torrecilla D, Lozano M V, Lallana E, Neissa J I, Novoa-Carballal N, Vidal A, Fernandez-Megia E, Torres D, Tiguera R, Alonso M J, Dominguez F. Eur. J. Pharm. Biopharm., 2013, 83:330.
[75] Yang P, Li D, Jin S, Ding J, Shi W B, Wang C C. Biomaterials, 2014, 35:2079.
[76] Gu Z, Yan M, Hu B, Joo K I, Biswas A, Lu Y F, Wang P, Tang Y. Nano Lett., 2009, 9:4533.
[77] Zhao M X, Hu B L, Gu Z, Joo K I, Wang P, Tang Y. Nano Today, 2013, 8:11.
[78] Villegas M R, Baeza A, Vallet R M. ACS Appl. Mater. Inter., 2015, 7:24075.
[79] Kong S D, Zhang W, Lee J H, Brammer K, Lal R, Karin M, Jin S H. Nano Lett., 2010, 10:5088.
[80] Kim B, Han G, Toley B J, Kim C K, Rotello V M, Forbes N S. Nature Nanotech., 2010, 5:465.
[81] Adams G P, Schier R, McCall A M, Simmons H H, Horak E M, Alpaugh R K, Marks J D, Weiner L M. Cancer Res., 2001, 61:4750.
[82] Owen M R, Byrne H M, Lewis C E. J. Thero. Biol., 2004, 226:377.
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