Biopolym. Cell. 2019; 35(4):249-267.
Nanoparticles-based photosensitizers with effect of aggregation-induced emission
1Korneev O. V., 2Sakhno T. V., 2Korotkova I. V.
  1. Higher Medical Educational Institution of Ukraine "Ukrainian Medical Stomatological Academy"
    23, Shevchenko Str., Poltava, Ukraine, 36023
  2. Poltava State Agrarian Academy
    1/3, Skovoroda Str., Poltava, Ukraine, 36000


Photodynamic therapy (PDT) is a method of the treatment of localized cancers, based on aphotochemical reaction between a light-activated molecule or photosensitizer (PS), light, andmolecular oxygen. Correct choice of PS is of fundamental importance for PDT efficacy. Despite numerous studies in this field, most known PS have some drawbacks, e.g. lack of specificity and aggregation in aqueous media. Consequently, the search for an ideal PS is essential for further development of PDT. Here we review classification and analyse main features of different generations of PS and describe the mechanisms of their action. Various methods of targeted delivery of PS to tumor cells are discussed. The advantages of PS nanoparticles with the effect of aggregation-induced emission (AIE) over the classic photosensitizers are presented. A possibility of practical application of such light-emitting structures in cancer phototherapy is shown
Keywords: photodynamic therapy (PDT), photosensitizer, aggregation-induced emission


[1] Raab O. Über die Wirkung fluorescieren der Stoffe auf Infusorien. Ztg Biol. 1900; 39: 524-6.
[2] Von Tappeiner H, Jesionek H. Therapeutische versuche mit fluoreszierenden stoffen. Munch Med Wochenschr. 1903; 47:2042–4.
[3] Von Tappeiner HA, Jodlbauer A. Die SensibilisierendeWirkung Fluorescierender Substanzen: Gesammelte Untersuchungen Über die Photodynamische Erscheinung. Leipzig, Germany: F.C.W. Vogel, 1907:p 210.
[4] Dougherty TJ, Grindey GB, Fiel R, Weishaupt KR, Boyle DG. Photoradiation therapy. II. Cure of animal tumors with hematoporphyrin and light. J Natl Cancer Inst. 1975;55(1):115-21.
[5] Dougherty TJ. Photodynamic therapy--new approaches. Semin Surg Oncol. 1989;5(1):6-16. Review.
[6] Kennedy JC, Marcus SL, Pottier RH. Photodynamic therapy (PDT) and photodiagnosis (PD) using endogenous photosensitization induced by 5-aminolevulinic acid (ALA): mechanisms and clinical results. J Clin Laser Med Surg. 1996;14(5):289-304. Review.
[7] Barashkov NN, Sakhno TV, Nurmukhametov RN, Khakhel' OA. Excimers of organic molecules. Russ Chem Rev. 1993; 62(6): 539-52.
[8] Korotkova IV, Sakhno TV, Barashkov NN. A quantum-chemical study of the influence of changes in the geometry of nitrogen-containing heterocyclic compounds on their fluorescent characteristics. Russ J Phys Chem A. 1999; 73(1): 83-6.
[9] Stennett EM, Ciuba MA, Levitus M. Photophysical processes in single molecule organic fluorescent probes. Chem Soc Rev. 2014;43(4):1057-75.
[10] Plotnikov VG. Theoretical foundations of the classification of molecules by luminescence spectra. Russ Chem Rev. 1980; 49(2): 172-89.
[11] Barashkov NN, Korotkova IV, Sakhno TV. Spectral manifestations of aggregates structure of heteroaromatic molecules at low temperatures. J Lumin. 2000; 87-89: 794-6.
[12] Korotkova IV, Sakhno TV, Barashkov NN. Theoretical study of radiationless deactivation of a series of coumarin derivatives. Theor Exp Chem. 1997; 33(2): 90-4.
[13] Grynyov BV, Sakhno TV, Senchishin VG. Optically transparent and fluorescent polymers. Kharkiv Institute of single crystals 2003; 575 p.
[14] Muehlmann LA, Ma BC, Longo JP, Almeida Santos Mde F, Azevedo RB. Aluminum-phthalocyanine chloride associated to poly(methyl vinyl ether-co-maleic anhydride) nanoparticles as a new third-generation photosensitizer for anticancer photodynamic therapy. Int J Nanomedicine. 2014;9:1199-213.
[15] Foote CS. Definition of type I and type II photosensitized oxidation. Photochem Photobiol. 1991;54(5):659.
[16] Hamblin MR, Newman EL. On the mechanism of the tumour-localising effect in photodynamic therapy. J Photochem Photobiol B. 1994;23(1):3-8. Review.
[17] Hudson R, Boyle RW. Strategies for selective delivery of photodynamic sensitisers to biological targets. J Porphyr Phthalocyanines. 2004; 8(7): 954-75.
[18] Minaev BF, Yashchuk LB. Possible electronic mechanisms of generation and quenching of luminescence of singlet oxygen in the course of photodynamic therapy: ab initio study. Biopolym Cell. 2006; 22(3): 231-5.
[19] Bregnhøj M, Westberg M, Minaev BF, Ogilby PR. Singlet oxygen photophysics in liquid solvents: converging on a unified picture. Acc Chem Res. 2017;50(8):1920-1927.
[20] Minaev BF. Electronic mechanisms of molecular oxygen activation. Russ Chem Rev. 2007;76(11): 988–1010.
[21] Minaev B. Photochemistry and spectroscopy of singlet oxygen in solvents. Recent advances which support the old theory. Chem Chem Tech. 2016; 10(4S): 519-30
[22] Abrahamse H, Hamblin MR. New photosensitizers for photodynamic therapy. Biochem J. 2016;473(4):347-64.
[23] Triesscheijn M, Baas P, Schellens JH, Stewart FA. Photodynamic therapy in oncology. Oncologist. 2006;11(9):1034-44.
[24] Allison RR, Downie GH, Cuenca R, Hu XH, Childs CJ, Sibata CH. Photosensitizers in clinical PDT. Photodiagnosis Photodyn Ther. 2004;1(1):27-42.
[25] Allison RR, Moghissi K. Photodynamic therapy (PDT): PDT mechanisms. Clin Endosc. 2013;46(1):24-9.
[26] van Straten D, Mashayekhi V, de Bruijn HS, Oliveira S, Robinson DJ. Oncologic Photodynamic therapy: basic principles, current clinical status and future directions. Cancers (Basel). 2017;9(2). pii: E19. .
[27] Yi G, Hong SH, Son J, Yoo J, Park C, Choi Y, Koo H. Recent advances in nanoparticle carriers for photodynamic therapy. Quant Imaging Med Surg. 2018;8(4):433-443.
[28] Lipson RL, Baldes EJ. The photodynamic properties of a particular hematoporphyrin derivative. Arch Dermatol. 1960;82:508-16.
[29] Dougherty TJ, Kaufman JE, Goldfarb A, Weishaupt KR, Boyle D, Mittleman A. Photoradiation therapy for the treatment of malignant tumors. Cancer Res. 1978;38(8):2628-35.
[30] Taratula O, Schumann C, Duong T, Taylor KL, Taratula O. Dendrimer-encapsulated naphthalocyanine as a single agent-based theranostic nanoplatform for near-infrared fluorescence imaging and combinatorial anticancer phototherapy. Nanoscale. 2015;7(9):3888-902.
[31] Allémann E, Rousseau J, Brasseur N, Kudrevich SV, Lewis K, van Lier JE. Photodynamic therapy of tumours with hexadecafluoro zinc phthalocynine formulated in PEG-coated poly(lactic acid) nanoparticles. Int J Cancer. 1996;66(6):821-4.
[32] Moghimi SM, Hunter AC, Murray JC. Long-circulating and target-specific nanoparticles: theory to practice. Pharmacol Rev. 2001;53(2):283-318.
[33] Kim H, Chung K, Lee S, Kim DH, Lee H. Near-infrared light-responsive nanomaterials for cancer theranostics. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2016;8(1):23-45.
[34] Gamaleia NF, Shton IO. Gold mining for PDT: Great expectations from tiny nanoparticles. Photodiagnosis Photodyn Ther. 2015;12(2):221-31.
[35] Hong SH, Kim H, Choi Y. Indocyanine green-loaded hollow mesoporous silica nanoparticles as an activatable theranostic agent. Nanotechnology. 2017;28(18):185102.
[36] Chen B, Pogue BW, Hasan T. Liposomal delivery of photosensitising agents. Expert Opin Drug Deliv. 2005;2(3):477-87.
[37] Hadinoto K, Sundaresan A, Cheow WS. Lipid-polymer hybrid nanoparticles as a new generation therapeutic delivery platform: a review. Eur J Pharm Biopharm. 2013;85(3 Pt A):427-43. ttps://
[38] Hong EJ, Choi DG, Shim MS. Targeted and effective photodynamic therapy for cancer using functionalized nanomaterials. Acta Pharm Sin B. 2016;6(4):297-307.
[39] Son J, Yang SM, Yi G, Roh YJ, Park H, Park JM, Choi MG, Koo H. Folate-modified PLGA nanoparticles for tumor-targeted delivery of pheophorbide a in vivo. Biochem Biophys Res Commun. 2018;498(3):523-528.
[40] Yoon HY, Koo H, Choi KY, Lee SJ, Kim K, Kwon IC, Leary JF, Park K, Yuk SH, Park JH, Choi K. Tumor-targeting hyaluronic acid nanoparticles for photodynamic imaging and therapy. Biomaterials. 2012;33(15):3980-9.
[41] Mei J, Leung NL, Kwok RT, Lam JW, Tang BZ. Aggregation-Induced Emission: Together we shine, united we soar! Chem Rev. 2015;115(21):11718-940.
[42] Granchak VM, Sakhno TV, Korotkova IV, Sakhno YuE, Kuchmy SYa. Aggregation-induced emission in organic nanoparticles: properties and applications: a review. Theoretical and Experimental Chemistry. 2018; 54(3): 147–77.
[43] Hong SH, Kim H, Choi Y. Enhanced fluorescence imaging and photodynamic cancer therapy using hollow mesoporous nanocontainers. Chem Asian J. 2017;12(14):1700-1703.
[44] Luo J, Xie Z, Lam JW, Cheng L, Chen H, Qiu C, Kwok HS, Zhan X, Liu Y, Zhu D, Tang BZ. Aggregation-induced emission of 1-methyl-1,2,3,4,5-pentaphenylsilole. Chem Commun (Camb). 2001;(18):1740-1.
[45] An BK, Kwon SK, Jung SD, Park SY. Enhanced emission and its switching in fluorescent organic nanoparticles. J Am Chem Soc. 2002;124(48):14410-5.
[46] Qin W, Dan D, Liu J, Yuan W, Hu Y, Liu B, Tang BZ. Biocompatible nanoparticles with aggregation‐induced emission characteristics as far‐red/near‐infrared fluorescent bioprobes for in vitro and in vivo imaging applications. Adv Funct Mater. 2012; 22(4): 771–9.
[47] Li K, Qin W, Ding D, Tomczak N, Geng J, Liu R, Liu J, Zhang X, Liu H, Liu B, Tang BZ. Photostable fluorescent organic dots with aggregation-induced emission (AIE dots) for noninvasive long-term cell tracing. Sci Rep. 2013;3:1150.
[48] Ding D, Mao D, Li K, Wang X, Qin W, Liu R, Chiam DS, Tomczak N, Yang Z, Tang BZ, Kong D, Liu B. Precise and long-term tracking of adipose-derived stem cells and their regenerative capacity via superb bright and stable organic nanodots. ACS Nano. 2014;8(12):12620-31.
[49] Yan L, Zhang Y, Xu B, Tian W. Fluorescent nanoparticles based on AIE fluorogens for bioimaging. Nanoscale. 2016;8(5):2471-87.
[50] Liu J, Chen C, Ji S, Liu Q, Ding D, Zhao D, Liu B. Long wavelength excitable near-infrared fluorescent nanoparticles with aggregation-induced emission characteristics for image-guided tumor resection. Chem Sci. 2017;8(4):2782-2789.
[51] Yuan Y, Feng G, Qin W, Tang BZ, Liu B. Targeted and image-guided photodynamic cancer therapy based on organic nanoparticles with aggregation-induced emission characteristics. Chem Commun (Camb). 2014;50(63):8757-60.
[52] Li M, Gao Y, Yuan Y, Wu Y, Song Z, Tang BZ, Liu B, Zheng QC. One-step formulation of targeted aggregation-induced emission dots for image-guided photodynamic therapy of cholangiocarcinoma. ACS Nano. 2017;11(4):3922-3932. PubMed PMID: 28383899.
[53] Feng G, Qin W, Hu Q, Tang BZ, Liu B. Cellular and mitochondrial dual-targeted organic dots with aggregation-induced emission characteristics for image-guided photodynamic therapy. Adv Healthc Mater. 2015;4(17):2667-76.
[54] Jayaram DT, Ramos-Romero S, Shankar BH, Garrido C, Rubio N, Sanchez-Cid L, Gómez SB, Blanco J, Ramaiah D. In vitro and in vivo demonstration of photodynamic activity and cytoplasm imaging through tpe nanoparticles. ACS Chem Biol. 2016;11(1):104-12.
[55] Perry SW, Norman JP, Barbieri J, Brown EB, Gelbard HA. Mitochondrial membrane potential probes and the proton gradient: a practical usage guide. Biotechniques. 2011;50(2):98-115.
[56] Zhao N, Chen S, Hong Y, Tang BZ. A red emitting mitochondria-targeted AIE probe as an indicator for membrane potential and mouse sperm activity. Chem Commun (Camb). 2015;51(71):13599-602.
[57] Gu B, Wu W, Xu G, Feng G, Yin F, Chong PHJ, Qu J, Yong KT, Liu B. Precise Two-photon photodynamic therapy using an efficient photosensitizer with aggregation-induced emission characteristics. Adv Mater. 2017;29(28).
[58] Guan Y, Lu H, Li W, Zheng Y, Jiang Z, Zou J, Gao H. Near-infrared triggered upconversion polymeric nanoparticles based on aggregation-induced emission and mitochondria targeting for photodynamic cancer therapy. ACS Appl Mater Interfaces. 2017;9(32):26731-26739.
[59] Zheng Y, Lu H, Jiang Z, Guan Y, Zou J, Wang X, Cheng R, Gao H. Low-power white light triggered AIE polymer nanoparticles with high ROS quantum yield for mitochondria-targeted and image-guided photodynamic therapy. J Mater Chem B. 2017; 5(31): 6277−81.
[60] Decock J, Obermajer N, Vozelj S, Hendrickx W, Paridaens R, Kos J. Cathepsin B, cathepsin H, cathepsin X and cystatin C in sera of patients with early-stage and inflammatory breast cancer. Int J Biol Markers. 2008;23(3):161-8.
[61] Yuan Y, Zhang CJ, Gao M, Zhang R, Tang BZ, Liu B. Specific light-up bioprobe with aggregation-induced emission and activatable photoactivity for the targeted and image-guided photodynamic ablation of cancer cells. Angew Chem Int Ed Engl. 2015;54(6):1780-6.
[62] Han K, Wang SB, Lei Q, Zhu JY, Zhang XZ. Ratiometric Biosensor for Aggregation-induced emission-guided precise photodynamic therapy. ACS Nano. 2015;9(10):10268-77.
[63] Sun X, Zebibula A, Dong X, Li G, Zhang G, Zhang D, Qian J, He S. Targeted and imaging-guided in vivo photodynamic therapy of tumors using dualfunctional, aggregation-induced emission nanoparticles. Nano Research. 2018; 11(5): 2756–70.
[64] Ravotto L, Ceroni P. Aggregation-induced phosphorescence of metal complexes: from principles to applications. Coord Chem Rev. 2017; 346: 62-76.
[65] Sathish V, Ramdass A, Thanasekaran P, Lu K-L. Aggregation-induced phosphorescence enhancement (AIPE) based on transition metal complexes—An overview. J. Photochem and Photobiology C: Photochemistry Reviews. 2015; 23: 25-44.
[66] Alam P, Dash S, Climent C, Kaur G, Choudhury AR, Casanova D, Alemany P, Chowdhury R, Laskar IR. Aggregation-induced emission’ active iridium(III) complexes with applications in mitochondrial staining. RSC Adv. 2017; 7: 5642-8.
[67] Liu Y, Song N, Chen L, Xie Z-G. BODIPY@Ir(III) complexes assembling organic nanoparticles for enhanced photodynamic therapy. Chin J Polymer Sci. 2018; 36(3): 417–424.