以上转换纳米颗粒和光动力疗法为基础的肿瘤联合治疗研究进展

doi:10.7517/j.issn.1674-0475.2016.04.297

摘要/Abstract

摘要：

光动力疗法作为一种非侵入性治疗手段已广泛应用于肿瘤的临床治疗。然而其疗效却深受紫外-可见光组织穿透深度的限制。镧系掺杂上转换纳米颗粒可以将近红外光转换为紫外-可见光,被广泛用于与传统光敏剂结合实现更为高效的光动力治疗。近年来,以上转换纳米颗粒和光动力疗法为基础的肿瘤联合治疗研究备受关注,本文重点介绍了该领域的最新研究进展,并对其未来发展方向作出了展望。

关键词: 光动力疗法, 上转换纳米颗粒, 联合疗法

Abstract:

Photodynamic therapy(PDT), a non-invasive treatment modality, has been widely used clinicallyagainst many types of cancers. However, its efficacy is heavily limited by the low tissue penetration depth of the UV-visible irradiation. Lanthanide-doped upconversion nanoparticles (UCNPs), which can convert near-infrared light to UV-visible light, have been used successfully to improve PDT activities of traditional photosensitizers. Recently, the combination therapy based on UCNPs-PDT is drawing increasing attention, and the related advances as well as perspectives have been presented in this review.

Key words: photodynamic therapy, upconversion nanoparticles, combination therapy

陈雨濛, 姜国玉, 王雪松. 以上转换纳米颗粒和光动力疗法为基础的肿瘤联合治疗研究进展[J]. 影像科学与光化学, 2016, 34(4): 297-311.

CHEN Yumeng, JIANG Guoyu, WANG Xuesong. Advances of Cancer Combination Therapy Based on Upconversion Nanoparticles and Photodynamic Therapy[J]. Imaging Science and Photochemistry, 2016, 34(4): 297-311.

参考文献

[1] Shanmugam V, Selvakumar S, Yeh C S. Near-infrared light-responsive nanomaterials in cancer therapeutics[J]. Chemical Society Reviews, 2014, 43:6254-6287.
[2] Cheng L, Wang C, Feng L, Yang K, Liu Z. Functional nanomaterials for phototherapies of cancer[J]. Chemical Reviews, 2014, 114:10869-10939.
[3] Shi E S, Hamada M, Murase N, Bi V. Nanomaterials formulations for photothermal and photodynamic therapy of cancer[J]. Journal of Photochemistry and Photobiology C: Photochemistry Reviews, 2013, 15:53-72.
[4] Master A, Livingston M, Gupta A S. Photodynamic nanomedicine in the treatment of solid tumors: perspectives and challenges[J]. Journal of Controlled Release, 2013, 168:88-102.
[5] Brown S B, Brown E A, Walker I.The present and future role of photodynamic therapy in cancer treatment[J]. The Lancet Oncology, 2004, 5:497-508.
[6] Zhu Z, Tang Z, Phillips J A.Yang R, Wang H, Tan W. Regulation of singlet oxygen generation using single-walled carbon nanotubes[J]. Journal of the American Chemical Society, 2008, 130:10856-10857.
[7] Lucky S S, Soo K C, Zhang Y. Nanoparticles in photodynamic therapy[J]. Chemical Reviews, 2015, 115:1990-2042.
[8] Lakshmanan S, Gupta G K, Avci P, Chandran R, Sadasivam M, Jorge A E S, Hamblin M R. Physical energy for drug delivery; poration, concentration and activation[J]. Advanced Drug Delivery Reviews, 2014, 71:98-114.
[9] Nishiyama N, Morimoto Y, Jang W D, Kataoka K. Design and development of dendrimer photosensitizer-incorporated polymeric micelles for enhanced photodynamic therapy[J]. Advanced Drug Delivery Reviews, 2009, 61:327-338.
[10] 雷万华,王雪松.光动力抗菌光敏剂的研究进展[J].影像科学与光化学, 2013, 31(5):321-334. Lei W H, Wang X S. Research progress of photodynamic antimicrobial photosensitizers[J]. Imaging Science and Photochemistry, 2013, 31(5):321-334.
[11] Lin L, Xiong L, Wen Y, Lei S, Deng X, Liu Z, Chen W, Miao X. Active targeting of nano-photosensitizer delivery systems for photodynamic therapy of cancer stem cells[J]. Journal of Biomedical Nanotechnology, 2015, 11:531-554.
[12] Kim J, Tung C H, Choi Y.Smart dual-functional warhead for folate receptor-specific activatable imaging and photodynamic therapy[J]. Chemical Communications, 2014,50:10600-10603.
[13] Yuan Y, Feng G, Qin W, Tang B Z, Liu B. Targeted and image-guided photodynamic cancer therapy based on organic nanoparticles with aggregation-induced emission characteristics[J]. Chemical Communications, 2014, 50:8757-8760.
[14] Chen M H, Ji L N, Mao Z W. Cyclometalated Ir(Ⅲ) complexes as targeted theranostic anticancer therapeutics: combining HDAC inhibition with photodynamic therapy[J]. Chemical Communications, 2014, 50:10945-10948.
[15] Lu K, He C, Lin W. Nanoscale metal-organic framework for highly effective photodynamic therapy of resistant head and neck cancer[J]. Journal of the American Chemical Society, 2014, 136:16712-16715.
[16] Synatschke C V, Nomoto T, Cabral H, Foörtsch M, Toh K, Matsumoto Y, Miyazaki K, Hanisch A, Schacher F H, Kishimura A.Multicompartment micelles with adjustable poly (ethylene glycol) shell for efficient in vivo photodynamic therapy[J]. ACS Nano, 2014, 8:1161-1172.
[17] Sosnik A, Carcaboso A M.Nanomedicines in the future of pediatric therapy[J]. Advanced Drug Delivery Reviews, 2014, 73:140-161.
[18] Ho M, Lo E, Young A, Liu D.Outcome of polypoidal choroidal vasculopathy at 1 year by combined therapy of photodynamic therapy with ranibizumab and predictive factors governing the outcome[J]. Eye, 2014, 28:1469-1476.
[19] Erikitola O, NwaobiR, Lotery A, Sivaprasad S.Photodynamic therapy for central serous chorioretinopathy[J]. Eye, 2014,28:944-957.
[20] Yang Y, Guo Q, Chen H, Zhou Z, Guo Z, Shen Z. Thienopyrrole-expanded BODIPY as a potential NIR photosensitizer for photodynamic therapy[J]. Chemical Communications, 2013, 49:3940-3942.
[21] Auzel F. Upconversion and anti-Stokes processes with f and d ions in solids[J]. Chemical Reviews, 2004, 35:139-173.
[22] Zhou J, Liu Q, Feng W, Sun Y, Li F Y. Upconversion nanophosphors for small-animal imaging[J]. Chemical Society Reviews, 2012, 41:1323-1349.
[23] Liu X G, Yan C H, John C. A. Photon upconversion nanomaterials[J]. Chemical Society Reviews, 2015, 44:1299-1301.
[24] Liu Q, Feng W, Li F. Water-soluble lanthanide upconversion nanophosphors: Synthesis and bioimaging applications in vivo[J]. Coordination Chemistry Reviews, 2014, 273:100-110.
[25] Yang D M,Ma P A,Hou Z Y,Chen Z Y,Li C X,Lin J.Current advances in lanthanide ion (Ln³⁺)-based upconversion nanomaterials for drug delivery[J]. Chemical Society Reviews, 2015, 44(6):1416-1448.
[26] Wu X, Chen G,Shen J, Li Z, Zhang Y,Han G. Upconversion nanoparticles: a versatile solution to multiscale biological imaging[J]. Bioconjugate Chemistry, 2015,26:166-175.
[27] Chao W, Liang C, Zhuang L.Upconversion nanoparticles for photodynamic therapy and other cancer therapeutics[J]. Theranostics, 2013, 3:317-330.
[28] Niagara Muhammad I, Akshaya B, Yong Z.Upconversion nanoparticles as versatile light nanotransducers for photoactivation applications[J]. Chemical Society Reviews, 2014, 44:1449-1478.
[29] Min Y Z,Li J M, Liu F, Yeow E, Xin B G. Near-infrared light-mediated photoactivation of a platinum antitumor prodrug and simultaneous cellular apoptosis imaging by upconversion-luminescent nanoparticles[J]. Angewandte Chemie International Edition, 2014, 53:1030-1034.
[30] Dou Q Q, Rengaramchandran A, Selvan S T, Paulmurugan R, Zhang Y. Core-shell upconversion nanoparticle-semiconductor heterostructures for photodynamic therapy[J]. Scientific Reports, 2015, 5:1-8.
[31] Zhang P, Steelant W, Kumar M, Scholfield M. Versatile photosensitizers for photodynamic therapy at infrared excitation[J]. Journal of the American Chemical Society, 2007, 129:4526-4527.
[32] Ungun B, Prud'Homme R K, Budijon S J, Shan J, Lim S F, Ju Y, Austin R. Nanofabricated upconversion nanoparticles for photodynamic therapy[J]. Optics Express, 2009, 17:80-86.
[33] Qian H S, Guo H C, Ho P C L, Mahendran R, Zhang Y. Mesoporous-silica-coated up-conversion fluorescent nanoparticles for photodynamic therapy[J]. Small, 2009, 5:2285-2290.
[34] Wang C, Tao H, Cheng L, Liu Z. Near-infrared light induced in vivo photodynamic therapy of cancer based on upconversion nanoparticles[J]. Biomaterials, 2011, 32:6145-6154.
[35] Liu K, Liu X, Zeng Q, Zhang Y, Tu L, Liu T, Kong X, Wang Y, Cao F, Lambrechts S A. Covalently assembled NIR nanoplatform for simultaneous fluorescence imaging and photodynamic therapy of cancer cells[J]. ACS Nano, 2012, 6:4054-4062.
[36] Tu D, Liu Y, Zhu H, Chen X. Optical/magnetic multimodal bioprobes based on lanthanide-doped inorganic nanocrystals[J]. Chemistry-A European Journal, 2013, 19:5516-5527.
[37] Xu Q C, Zhang Y, Tan M J, Liu Y, Yuan S, Choong C, Tan N S, Tan T T Y. Anti-cAngptl4 Ab-conjugated N-TiO₂/NaYF₄:Yb, Tm nanocomposite for near infrared-triggered drug release and enhanced targeted cancer cell ablation[J]. Advanced Healthcare Materials, 2012,1(4):470-474.
[38] Zhou A, Wei Y, Wu B, Chen Q, Xing D. Pyropheophorbide A and c (RGDyK) comodified chitosan-wrapped upconversion nanoparticle for targeted near-infrared photodynamic therapy[J]. Molecular Pharmaceutics, 2012, 9:1580-1589.
[39] Qiao X F, Zhou J C, Xiao J W, Wang Y F, Sun L D, Yan C H. Triple-functional core-shell structured upconversion luminescent nanoparticles covalently grafted with photosensitizer for luminescent, magnetic resonance imaging and photodynamic therapy in vitro[J]. Nanoscale, 2012, 4:4611-4623.
[40] Liu X, Zheng M, Kong X, Zhang Y, Zeng Q, Sun Z, Buma W J, Zhang H. Separately doped upconversion-C 60 nanoplatform for NIR imaging-guided photodynamic therapy of cancer cells[J]. Chemical Communications, 2013, 49:3224-3226.
[41] Jin S, Zhou L, Gu Z, Tian G, Yan L, Ren W, Yin W, Liu X, Zhang X, Hu Z. A new near infrared photosensitizing nanoplatform containing blue-emitting up-conversion nanoparticles and hypocrellin A for photodynamic therapy of cancer cells[J]. Nanoscale, 2013, 5:11910-11918.
[42] Yuan Q, Wu Y, Wang J, Lu D, Zhao Z, Liu T, Zhang X, Tan W. Targeted bioimaging and photodynamic therapy nanoplatform using an aptamer-guided G-Quadruplex DNA carrier and near-infrared light[J]. Angewandte Chemie International Edition, 2013, 52:13965-13969.
[43] Chou T C. Drug combination studies and their synergy quantification using the chou-talalay method[J]. Cancer Research, 2010, 70:440-446.
[44] Xin D, Tan C. Combination of microRNA therapeutics with small-molecule anticancer drugs: mechanism of action and co-delivery nanocarriers[J]. Advanced Drug Delivery Reviews, 2015, 81:184-197.
[45] Lehár J, Krueger A S, Avery W, Heilbut A M, Johansen L M, Price E R, Rickles R J, ShortIIii G F, Staunton J E, Jin X. Synergistic drug combinations tend to improve therapeutically relevant selectivity[J]. Nature Biotechnology, 2009, 27:659-666.
[46] Greco F, Vicent M J. Combination therapy: opportunities and challenges for polymer-drug conjugates as anticancer nanomedicines[J]. Advanced Drug Delivery Reviews, 2009, 61:1203-1213.
[47] Lammers T. Improving the efficacy of combined modality anticancer therapy using HPMA copolymer-based nanomedicine formulations[J]. Advanced Drug Delivery Reviews, 2010, 62:203-230.
[48] Tian G, Ren W, Yan L, Jian S, Gu Z, Zhou L, Jin S, Yin W, Li S, Zhao Y. Red-emitting upconverting nanoparticles for photodynamic therapy in cancer cells under near-infrared excitation[J]. Small, 2013,9:1929-1938.
[49] Idris N M, Gnanasammandhan M K, Zhang J, Ho P C, Mahendran R, Zhang Y. In vivo photodynamic therapy using upconversion nanoparticles as remote-controlled nanotransducers[J]. Nature Medicine, 2012, 18:1580-1585.
[50] Xing H, Zheng X, Ren Q, Bu W, Ge W, Xiao Q, Zhang S, Wei C, Qu H, Wang Z. Computed tomography imaging-guided radiotherapy by targeting upconversion nanocubes with significant imaging and radiosensitization enhancements[J]. Scientific Reports, 2013, 3:1-9.
[51] Severyn B, Liehr R A, Wolicki A, Nguyen K H, Hudak E M, Ferrer M, Caldwell J S, Hermes J D, Jing L, Tudor M. Parsimonious discovery of synergistic drug combinations[J]. ACS Chemical Biology, 2011, 6:1391-1398.
[52] Chen Q, Wang X, Wang C, Feng L, Li Y, Liu Z. Drug-induced self-assembly of modified albumins as nano-theranostics for tumor-targeted combination therapy[J]. ACS Nano, 2015,9:5223.
[53] Tian G, Gu Z J, Zhou L J,Yin W Y,Liu X X,Yan L,Jin S,Ren W L,Xin G M,Li S J.Mn²⁺ dopant-controlled synthesis of NaYF₄:Yb/Er upconversion nanoparticles for in vivo imaging and drug delivery[J]. Advanced Materials, 2012, 24(9):1226-1231.
[54] Chatterjee D, Fong L, Zhang Y. Nanoparticles in photodynamic therapy: an emerging paradigm[J]. Advanced Drug Delivery Reviews, 2008, 60:1627-1637.
[55] Yuan Y, Min Y, Hu Q, Xing B, Liu B. NIR photoregulated chemo-and photodynamic cancer therapy based on conjugated polyelectrolyte-drug conjugate encapsulated upconversion nanoparticles[J]. Nanoscale, 2014, 6(19):11259-11272.
[56] Yuan H X,Chong H,Wang B,Zhu C L,Liu L B,Yang Q,Lv F T,Wang S. Chemical molecule-induced light-activated system for anticancer and antifungal activities[J]. Journal of the American Chemical Society, 2012, 134(32):13184-13187.
[57] Yang S,Li N J,Liu Z,Sha W W,Chen D J,Xu Q F,Lu J M. Amphiphilic copolymer coated upconversion nanoparticles for near-infrared light-triggered dual anticancer treatment[J]. Nanoscale,2014, 6(24):14903-14910.
[58] Dumitru A, Larisa K, Andriy M. 1,9-Dialkoxyanthracene as a ¹O₂-sensitive linker[J]. Journal of the American Chemical Society, 2011, 133(11), 3972-3980.
[59] Lucky S S, Soo K C, Zhang Y. Nanoparticles in photodynamic therapy[J]. Chemical Reviews, 2015, 115:1990-2042.
[60] Liu X M,Zheng M,Kong X G,Zhang Y L,Zeng Q H,Sun Z C,Buma W J,Zhang H. Separately doped upconversion-C60 nanoplatform for NIR imaging-guided photodynamic therapy of cancer cells[J]. Chemical Communications, 2013, 49(31):3224-3226.
[61] Cheng L, Wang C, Feng L Z, Yang K, Liu Z. Functional nanomaterials for phototherapies of cancer[J]. Chemical Reviews, 2014, 114(21):10869-10939.
[62] Yong Y,Zhou L J,Gu Z J,Yan L,Tian G,Zheng X P,Liu X D,Zhang X,Shi J X,Cong W S. WS₂ nanosheet as a new photosensitizer carrier for combined photodynamic and photothermal therapy of cancer cells[J]. Nanoscale, 2014, 6(17):10394-10403.
[63] Bo T, Chao W, Shuai Z, Feng L, Zhuang L. Photothermally enhanced photodynamic therapy delivered by nano-graphene oxide[J]. ACS Nano, 2011, 5:7000-7009.
[64] Wang Y, Wang H, Liu D, Song S, Xiao W, Zhang H. Graphene oxide covalently grafted upconversion nanoparticles for combined NIR mediated imaging and photothermal/photodynamic cancer therapy[J]. Biomaterials, 2013, 34:7715-7724.
[65] Chen Q, Wang C, Cheng L, He W, Cheng Z, Liu Z. Protein modified upconversion nanoparticles for imaging-guided combined photothermal and photodynamic therapy[J]. Biomaterials, 2014, 35:2915-2923.
[66] Yin M, Li Z, Ju E, Wang Z, Dong K, Ren J, Qu X. Multifunctional upconverting nanoparticles for near-infrared triggered and synergistic antibacterial resistance therapy[J]. Chemical Communications, 2014, 50:10488-10490.
[67] Xiao Z Y. Cu S nanoparticles: clinically favorable materials for photothermal applications[J]. Nanomedicine, 2014, 9(3): 373-375.
[68] Mintzer M, Simanek E. Nonviral vectors for gene delivery[J]. Chemical Reviews, 2009, 109:259-302.
[69] Ozcan G, Ozpolat B, Coleman R L, Sood A K, Lopez B G. Preclinical and clinical development of siRNA-based therapeutics[J]. Advanced Drug Delivery Reviews, 2015, 87: 108-119.
[70] Neus F M, Esther V, Antonio V. Membrane-active peptides for non-viral gene therapy: making the safest easier[J]. Trends in Biotechnology, 2008, 26:267-275.
[71] Mellert K, Lamla M, Scheffzek K, Wittig R, Kaufmann D. Enhancing endosomal escape of transduced proteins by photochemical internalisation[J]. Plos One, 2012, 7:52473-52473.
[72] Jayakumar M K, Bansal A, Huang K, Yao R, Li B N, Zhang Y. Near-infrared-light-based nanoplatform boosts endosomal escape and controls gene knockdown in vivo[J]. ACS Nano, 2014, 8(5):4848-4858.
[73] Wang X, Liu K, Yang G, Cheng L, He L, Liu Y, Li Y, Guo L, Liu Z. Near-infrared light triggered photodynamic therapy in combination with gene therapy using upconversion nanoparticles for effective cancer cell killing[J]. Nanoscale, 2014, 6:9198-9205.
[74] Gu W Y,Jia Z F, Truong N P, Indira P, Yin X, Monteiro M J. Polymer nanocarrier system for endosome escape and timed release of siRNA with complete gene silencing and cell death in cancer cells[J]. Biomacromolecules, 2013, 14(10):3386-3389.
[75] Juliette T, Jean M H L, Arthur S M, Te V, Jean P G. Past, present, and future of radiotherapy for the benefit of patients[J]. Nature Reviews Clinical Oncology, 2013, 10:52-60.
[76] Hainfeld J F, Avraham D F, Slatkin D N, Smilowitz H M. Radiotherapy enhancement with gold nanoparticles[J]. Journal of Pharmacy & Pharmacology, 2008, 60:977-985.
[77] Fan W P,Shen B,Bu W B,Chen F,He Q J,Zhao K L,Zhang S J,Zhou L P,Peng W J,Xiao Q F,Ni D L, Liu J N,Shi J L. A smart upconversion-based mesoporous silica nanotheranostic system for synergetic chemo-/radio-/photodynamic therapy and simultaneous MR/UCL imaging[J]. Biomaterials, 2014, 35(32):8992-9002.
[78] Zhang C, Zhao K L, Bu W B, Ni D L, Liu Y Y, Feng J W, Shi J L. Marriage of scintillator and semiconductor for synchronous radiotherapy and deep photodynamic therapy with diminished oxygen dependence[J]. Angewandte Chemie, 2015, 54(6):1770-1774.
[79] Lü R, Yang P, He F, Gai S, Li C, Dai Y, Yang G, Lin J. A yolk-like multifunctional platform for multimodal imaging and synergistic therapy triggered by a single near-infrared light[J]. ACS Nano, 2015, 9:1630-1647.
[80] Jaque D, Maestro L M, Del R B, Haro G P, Benayas A, Plaza J, Rodr guez E M, Sol J G. Nanoparticles for photothermal therapies[J]. Nanoscale, 2014, 6:9494-9530.
[81] Wang Y F, Liu G Y, Sun L D, Xiao J W, Zhou J C, Yan C H. Nd³⁺-sensitized upconversion nanophosphors: Efficient in vivo bioimaging probes with minimized heating effect[J]. ACS Nano, 2013, 7(8):7200-7206.
[82] Zhan Q, Qian J, Liang H, Somesfalean G, Wang D, He S, Zhang Z, Andersson E S. Using 915 nm laser excited Tm³⁺/Er³⁺/Ho³⁺-doped NaYbF₄ upconversion nanoparticles for in vitro and deeper in vivo bioimaging without overheating irradiation[J]. ACS Nano, 2011, 5(5):3744-3757.
[83] Zou W, Visser C, Maduro J A, Pshenichnikov M S, Hummelen J C. Broadband dye-sensitized upconversion of near-infrared light[J]. Nature Photonics, 2012, 6:560-564.
[84] Jayakumar M K, Idris N M, Huang K, Zhang Y. A paradigm shift in the excitation wavelength of upconversion nanoparticles[J]. Nanoscale, 2014, 6:8441-8443.
[85] Sun Y, Feng W, Yang P, Huang C, Li F Y. The biosafety of lanthanide upconversion nanomaterials[J]. Chemical Society Reviews, 2015, 44:1509-1525.
[86] Conner S D, Schmid S L. Regulated portals of entry into the cell[J]. Nature, 2003, 422:37-44.
[87] Durymanov M O, Rosenkranz A A, Sobolev A S. Current approaches for improving intratumoral accumulation and distribution of nanomedicines[J]. Theranostics, 2015, 5:1007-1020.
[88] Jin J, Gu Y J, Man C W Y, Cheng J, Xu Z, Zhang Y, Wang H, Lee V H Y, Cheng S H, Wong W T. Polymer-coated NaYF₄:Yb³⁺, Er³⁺ upconversion nanoparticles for charge-dependent cellular imaging[J]. ACS Nano, 2011, 5(10):7838-7847.
[89] Liu C, Hou Y, Gao M. Are rare-earth nanoparticles suitable for in vivo applications[J]. Advanced Materials, 2014, 26:6922-6932.
[90] Gnach A, Lipinski T, Bednarkiewicz A, Rybka J, CapobiancoJA. Upconverting nanoparticles: assessing the toxicity[J]. Chemical Society Reviews, 2015, 44:1561-1584.
[91] Chen Y M, Jiang G Y, Zhou Q X, Zhang Y Y, Li K, Zheng Y, Zhang B W, Wang X S. An upconversion nano-particle/Ru(Ⅱ) polypyridyl complex assembly for NIR-activated release of a DNA covalent-binding agent[J]. RSC Advances, 2016, 6(28):23804-23808.