Conjugated Polymer Nanotherapeutics for Next Generation Photodynamic Therapy

Main Article Content

Andre Gesquiere Khalaf Jasim Martin Topps Sajan Shroff Alondra M Ortiz Ortiz Olivia George Yasmine Abdellatif

Abstract

First and second-generation photosensitizers for Photodynamic Therapy (PDT) are in clinical trials, with a few approved for clinical application. While effective, several drawbacks have remained unaddressed that could increase the impact of PDT as an efficient therapy, including lack of selectivity to diseased tissue, toxicity, low to moderate light absorption, and poor solubility of the sensitizers that results in low bioavailability. It’s likely that a new generation of PDT sensitizers must be developed to improve on these shortcomings.


In this review, we summarize our progress in the development of Conjugated Polymer Nanoparticles as a next generation nanotherapeutic for Photodynamic Therapy (PDT). We show that their unprecedented light absorption, efficient ROS generation, high level of targeted delivery and selective uptake, absence of dark toxicity and high percentage of PDT induced cell mortality observed indicate a promising next generation PDT sensitizer. The simple design and ease of fabrication of the Conjugated Polymer Nanoparticles holds promise for broad applicability.

Article Details

How to Cite
GESQUIERE, Andre et al. Conjugated Polymer Nanotherapeutics for Next Generation Photodynamic Therapy. Medical Research Archives, [S.l.], v. 6, n. 2, feb. 2018. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/1673>. Date accessed: 28 mar. 2024. doi: https://doi.org/10.18103/mra.v6i2.1673.
Section
Review Articles

References

[1] Dent, S.; Oyan, B.; Honig, A.; Mano, M.; Howell, S. HER2-targeted therapy in breast cancer: A systematic review of neoadjuvant trials. Cancer Treat. Rev. 2013, 39, 622-631.
[2] Heinemann, V.; Douillard, J. Y.; Ducreux, M.; Peeters, M. Targeted therapy in metastatic colorectal cancer - An example of personalised medicine in action. Cancer Treat. Rev. 2013, 39, 592-601.
[3] Mountzios, G.; Soultati, A.; Pectasides, D.; Pectasides, E.; Dimopoulos, M. A.; Papadimitriou, C. A. Developments in the systemic treatment of metastatic cervical cancer. Cancer Treat. Rev. 2013, 39, 430-443.
[4] Verbrugghe, M.; Verhaeghe, S.; Lauwaert, K.; Beeckman, D.; Van Hecke, A. Determinants and associated factors influencing medication adherence and persistence to oral anticancer drugs: A systematic review. Cancer Treat. Rev. 2013, 39, 610-621.
[5] Xie, X.; Wang, S. S.; Wong, T. C. S.; Fung, M. C. Genistein promotes cell death of ethanol-stressed HeLa cells through the continuation of apoptosis or secondary necrosis. Cancer Cell Int. 2013, 13, 1-15.
[6] Fisher, B.; Anderson, S.; Bryant, J.; Margolese, R. G.; Deutsch, M.; Fisher, E. R.; Jeong, J.-H.; Wolmark, N. Twenty-Year Follow-up of a Randomized Trial Comparing Total Mastectomy, Lumpectomy, and Lumpectomy plus Irradiation for the Treatment of Invasive Breast Cancer. New England Journal of Medicine 2002, 347, 1233-1241.
[7] Fong, Y.; Fortner, J.; Sun, R. L.; Brennan, M. F.; Blumgart, L. H. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Annals of surgery 1999, 230, 309-318; discussion 318-321.
[8] Ishitobi, M.; Suzuki, O.; Komoike, Y.; Ohsumi, S.; Nakahara, S.; Yagi, T.; Yoshinami, T.; Tomita, Y.; Inaji, H. Phase II study of neoadjuvant anastrozole and concurrent radiotherapy for postmenopausal breast cancer patients. Breast Cancer 2014, 21, 550-556.
[9] Kalbasi, A.; June, C. H.; Haas, N.; Vapiwala, N. Radiation and immunotherapy: a synergistic combination. J. Clin. Invest. 2013, 123, 2756-2763.
[10] Suneja, G.; Poorvu, P. D.; Hill-Kayser, C.; Lustig, R. A. Acute toxicity of proton beam radiation for pediatric central nervous system malignancies. Pediatr. Blood Cancer 2013, 60, 1431-1436.
[11] Kumar, A.; Cascarini, L.; McCaul, J. A.; Kerawala, C. J.; Coombes, D.; Godden, D.; Brennan, P. A. How should we manage oral leukoplakia? Br. J. Oral Maxillofac. Surg. 2013, 51, 377-383.
[12] Milovanovic, J.; Djukic, V.; Milovanovic, A.; Jotic, A.; Banko, B.; Jesic, S.; Babic, B.; Trivic, A.; Artiko, V.; Petrovic, M.; Stankovic, P. Clinical outcome of early glottic carcinoma in Serbia. Auris Nasus Larynx 2013, 40, 394-399.
[13] Moore, E. J.; Hinni, M. L. Critical Review: Transoral Laser Microsurgery and Robotic-Assisted Surgery for Oropharynx Cancer Including Human Papillomavirus-Related Cancer. Int. J. Radiat. Oncol. Biol. Phys. 2013, 85, 1163-1167.
[14] No, D.; Osterberg, E. C.; Otto, B.; Naftali, I.; Choi, B. Evaluation of continence following 532nm laser prostatectomy for patients previously treated with radiation therapy or brachytherapy. Lasers Surg. Med. 2013, 45, 358-361.
[15] Rosch, T. Progress in endoscopy: areas of current interest and topics to watch out for. Endoscopy 2012, 44, 1148-1157.
[16] Stummer, W.; Pichlmeier, U.; Meinel, T.; Wiestler, O. D.; Zanella, F.; Reulen, H.-J. r. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. The Lancet Oncology 2006, 7, 392-401.
[17] Troyan, S.; Kianzad, V.; Gibbs-Strauss, S.; Gioux, S.; Matsui, A.; Oketokoun, R.; Ngo, L.; Khamene, A.; Azar, F.; Frangioni, J. The FLARE Intraoperative Near-Infrared Fluorescence Imaging System: A First-in-Human Clinical Trial in Breast Cancer Sentinel Lymph Node Mapping. Annals of Surgical Oncology 2009, 16, 2943-2952.
[18] De Beer, E. L.; Bottone, A. E.; Voest, E. E. Doxorubicin and mechanical performance of cardiac trabeculae after acute and chronic treatment: a review. European Journal of Pharmacology 2001, 415, 1-11.
[19] Joseph, M. M. A., S. R. ;George, S. K. ;Pillai, K. R. ;Mini, S. ;Sreelekha, T. T. . Galactoxyloglucan-Modified Nanocarriers of Doxorubicin for Improved Tumor-Targeted Drug Delivery with Minimal Toxicity. Journal of Biomedical Nanotechnology 2014, 10, 3253-3268.
[20] Keizer, H. G.; Pinedo, H. M.; Schuurhuis, G. J.; Joenje, H. Doxorubicin (adriamycin): A critical review of free radical-dependent mechanisms of cytotoxicity. Pharmacology & Therapeutics 1990, 47, 219-231.
[21] Fagard, R.; Metelev, V.; Souissi, I. s.; Baran-Marszak, F. STAT3 inhibitors for cancer therapy: Have all roads been explored? JAK-STAT 2013, 2, e22882.
[22] Turkson, J. J., R. STAT proteins: novel molecular targets for cancer drug discovery. Oncogene 2000, 19, 6613-6626.
[23] Zhang, X.; Yue, P.; Page, B. D. G.; Li, T.; Zhao, W.; Namanja, A. T.; Paladino, D.; Zhao, J.; Chen, Y.; Gunning, P. T.; Turkson, J. Orally bioavailable small-molecule inhibitor of transcription factor Stat3 regresses human breast and lung cancer xenografts. Proceedings of the National Academy of Sciences 2012, 109, 9623-9628.
[24] Davis, M. E.; Chen, Z.; Shin, D. M. Nanoparticle therapeutics: an emerging treatment modality for cancer. Nature Reviews Drug Discovery 2008, 7, 771-782.
[25] Vyas, D. C., P. ;Saadeh, Y. ;Vyas, A. . The Role of Nanotechnology in Gastrointestinal Cancer. Journal of Biomedical Nanotechnology 2014, 10, 3204-3218.
[26] Brown, S. B.; Brown, E. A.; Walker, I. The present and future role of photodynamic therapy in cancer treatment. The Lancet Oncology 2004, 5, 497-508.
[27] Buinauskaite, E.; Maciulaitis, R.; Buinauskiene, J.; Valiukeviciene, S. Topical photodynamic therapy of actinic keratoses with 5-aminolevulinic acid: Randomized controlled trial with six months follow-up. Journal of Dermatological Treatment 2014, 25, 519-522.
[28] Casie Chetty, N.; Hemmant, B.; Skellett, A.-M. Periocular photodynamic therapy for squamous intra-epidermal carcinoma. Journal of Dermatological Treatment 2014, 25, 516-518.
[29] Gupta, A.; Avci, P.; Sadasivam, M.; Chandran, R.; Parizotto, N.; Vecchio, D.; de Melo, W.; Dai, T. H.; Chiang, L. Y.; Hamblin, M. R. Shining light on nanotechnology to help repair and regeneration. Biotechnol. Adv. 2012, 31, 607-631.
[30] Hopper, C. Photodynamic therapy: a clinical reality in the treatment of cancer. The Lancet Oncology 2000, 1, 212-219.
[31] Kubler, A. C. Photodynamic therapy. Medical Laser Application 2005, 20, 37-45.
[32] Dougherty, T. J.; Gomer, C. J.; Henderson, B. W.; Jori, G.; Kessel, D.; Korbelik, M.; Moan, J.; Peng, Q. Photodynamic therapy. J. Natl. Cancer Inst. 1998, 90, 889-905.
[33] Dolmans, D. E. J. G. J.; Fukumura, D.; Jain, R. K. Photodynamic therapy for cancer. Nat Rev Cancer 2003, 3, 380-387.
[34] Vrouenraets, M. B. V., G. W. M. ;Snow, G. B. ;van Dongen, Gams Basic principles, applications in oncology and improved selectivity of photodynamic therapy. Anticancer Research 2003, 23, 505-522.
[35] Wilson, B. C. Photodynamic therapy for cancer: Principles. Canadian Journal of Gastroenterology & Hepatology 2002, 16, 393 - 396.
[36] Shirasu, N.; Nam, S. O.; Kuroki, M. Tumor-targeted Photodynamic Therapy. Anticancer Research 2013, 33, 2823-2831.
[37] Lim, C.-K.; Heo, J.; Shin, S.; Jeong, K.; Seo, Y. H.; Jang, W.-D.; Park, C. R.; Park, S. Y.; Kim, S.; Kwon, I. C. Nanophotosensitizers toward advanced photodynamic therapy of Cancer. Cancer Letters 2013, 334, 176-187.
[38] Agostinis, P.; Berg, K.; Cengel, K. A.; Foster, T. H.; Girotti, A. W.; Gollnick, S. O.; Hahn, S. M.; Hamblin, M. R.; Juzeniene, A.; Kessel, D.; Korbelik, M.; Moan, J.; Mroz, P.; Nowis, D.; Piette, J.; Wilson, B. C.; Golab, J. Photodynamic Therapy of Cancer: An Update. Ca-a Cancer Journal for Clinicians 2011, 61, 250-281.
[39] Cheng, Y. H.; Cheng, H.; Jiang, C. X.; Qiu, X. F.; Wang, K. K.; Huan, W.; Yuan, A.; Wu, J. H.; Hu, Y. Q. Perfluorocarbon nanoparticles enhance reactive oxygen levels and tumour growth inhibition in photodynamic therapy. Nature Communications 2015, 6, 8785.
[40] Huang, Z.; Xu, H. P.; Meyers, A. D.; Musani, A. I.; Wang, L. W.; Tagg, R.; Barqawi, A. B.; Chen, Y. K. Photodynamic therapy for treatment of solid tumors - Potential and technical challenges. Technology in Cancer Research & Treatment 2008, 7, 309-320.
[41] Lee, K. L.; Carpenter, B. L.; Wen, A. M.; Ghiladi, R. A.; Steinmetz, N. F. High Aspect Ratio Nanotubes Formed by Tobacco Mosaic Virus for Delivery of Photodynamic Agents Targeting Melanoma. Acs Biomaterials Science & Engineering 2016, 2, 838-844.
[42] Wen, A. M.; Lee, K. L.; Cao, P. F.; Pangilinan, K.; Carpenter, B. L.; Lam, P.; Veliz, F. A.; Ghiladi, R. A.; Advincula, R. C.; Steinmetz, N. F. Utilizing Viral Nanoparticle/Dendron Hybrid Conjugates in Photodynamic Therapy for Dual Delivery to Macrophages and Cancer Cells. Bioconjugate Chemistry 2016, 27, 1227-1235.
[43] Chen, J.-Y.; Lee, Y.-M.; Zhao, D.; Mak, N.-K.; Wong, R. N.-S.; Chan, W.-H.; Cheung, N.-H. Quantum Dot-mediated Photoproduction of Reactive Oxygen Species for Cancer Cell Annihilation. Photochemistry and Photobiology 2010, 86, 431-437.
[44] Chou, K. L.; Meng, H.; Cen, Y.; Li, L.; Chen, J. Y. Dopamine-quantum dot conjugate: a new kind of photosensitizers for photodynamic therapy of cancers. J. Nanopart. Res. 2013, 15, 9.
[45] Huang, P.; Lin, J.; Wang, S.; Zhou, Z.; Li, Z.; Wang, Z.; Zhang, C.; Yue, X.; Niu, G.; Yang, M.; Cui, D.; Chen, X. Photosensitizer-conjugated silica-coated gold nanoclusters for fluorescence imaging-guided photodynamic therapy. Biomaterials 2013, 34, 4643-4654.
[46] Ito, S.; Miyoshi, N.; Degraff, W. G.; Nagashima, K.; Kirschenbaum, L. J.; Riesz, P. Enhancement of 5-Aminolevulinic acid-induced oxidative stress on two cancer cell lines by gold nanoparticles. Free Radical Research 2009, 43, 1214-1224.
[47] Vankayala, R.; Huang, Y.-K.; Kalluru, P.; Chiang, C.-S.; Hwang, K. C. First Demonstration of Gold Nanorods-Mediated Photodynamic Therapeutic Destruction of Tumors via Near Infra-Red Light Activation. Small 2013, 10, 1612-1622.
[48] Perrier, M.; Gary-Bobo, M.; Lartigue, L.; Brevet, D.; Morere, A.; Garcia, M.; Maillard, P.; Raehm, L.; Guari, Y.; Larionova, J.; Durand, J. O.; Mongin, O.; Blanchard-Desce, M. Mannose-functionalized porous silica-coated magnetic nanoparticles for two-photon imaging or PDT of cancer cells. J. Nanopart. Res. 2013, 15, 17.
[49] Wang, F.; Chen, X. L.; Zhao, Z. X.; Tang, S. H.; Huang, X. Q.; Lin, C. H.; Cai, C. B.; Zheng, N. F. Synthesis of magnetic, fluorescent and mesoporous core-shell-structured nanoparticles for imaging, targeting and photodynamic therapy. J. Mater. Chem. 2011, 21, 11244-11252.
[50] Kim, S.; Ohulchanskyy, T. Y.; Pudavar, H. E.; Pandey, R. K.; Prasad, P. N. Organically modified silica nanoparticles co-encapsulating photosensitizing drug and aggregation-enhanced two-photon absorbing fluorescent dye aggregates for two-photon photodynamic therapy. J. Am. Chem. Soc. 2007, 129, 2669-2675.
[51] Tao, X.; Yang, Y.-J.; Liu, S.; Zheng, Y.-Z.; Fu, J.; Chen, J.-F. Poly(amidoamine) dendrimer-grafted porous hollow silica nanoparticles for enhanced intracellular photodynamic therapy. Acta Biomaterialia 2013, 9, 6431-6438.
[52] Zhao, Z. X.; Huang, Y. Z.; Shi, S. G.; Tang, S. H.; Li, D. H.; Chen, X. L. Cancer therapy improvement with mesoporous silica nanoparticles combining photodynamic and photothermal therapy. Nanotechnology 2014, 25, 285701.
[53] Ohulchanskyy, T. Y.; Roy, I.; Goswami, L. N.; Chen, Y.; Bergey, E. J.; Pandey, R. K.; Oseroff, A. R.; Prasad, P. N. Organically Modified Silica Nanoparticles with Covalently Incorporated Photosensitizer for Photodynamic Therapy of Cancer. Nano Letters 2007, 7, 2835-2842.
[54] Xue, C.; Wu, J.; Lan, F.; Liu, W.; Yang, X.; Zeng, F.; Xu, H. Nano Titanium Dioxide Induces the Generation of ROS and Potential Damage in HaCaT Cells Under UVA Irradiation. Journal of Nanoscience and Nanotechnology 2010, 10, 8500-8507.
[55] Ding, H.; Mora, R.; Gao, J.; Sumer, B. D. Characterization and Optimization of mTHPP Nanoparticles for Photodynamic Therapy of Head and Neck Cancer. Otolaryngology -- Head and Neck Surgery 2011, 145, 612-617.
[56] Kameyama, N. M., S. ;Itano, O. ;Ito, A. ;Konno, T. ;Arai, T. ;Ishihara, K. ;Ueda, M. ;Kitagawa, Y. Photodynamic Therapy Using an Anti-EGF Receptor Antibody Complexed with Verteporfin Nanoparticles: A Proof of Concept Study. Cancer Biotherapy and Radiopharmaceuticals 2011, 26, 697-704.
[57] Derycke, A. S. L.; de Witte, P. A. M. Liposomes for photodynamic therapy. Adv. Drug Deliv. Rev. 2004, 56, 17-30.
[58] Choi, K. H. C., C. W. ;Kim, C. H. ;Kim, D. H. ;Jeong, Y. I. ;Kang, D. H. . Effect of 5-Aminolevulinic Acid-Encapsulate Liposomes on Photodynamic Therapy in Human Cholangiocarcinoma Cells. Journal of Nanoscience and Nanotechnology 2014, 14, 5628-5632.
[59] Figueira, F. v.; M.R. Pereira, P.; Silva, S.; A.S. Cavaleiro, J.; P.C. Tome, J. Porphyrins and Phthalocyanines Decorated with Dendrimers: Synthesis and Biomedical Applications. Current Organic Synthesis 2014, 11, 110-126.
[60] Taratula, O.; Schumann, C.; Naleway, M. A.; Pang, A. J.; Chon, K. J.; Taratula, O. A Multifunctional Theranostic Platform Based on Phthalocyanine-Loaded Dendrimer for Image-Guided Drug Delivery and Photodynamic Therapy. Molecular Pharmaceutics 2013, 10, 3946-3958.
[61] Grimland, J. L.; Wu, C.; Ramoutar, R. R.; Brumaghim, J. L.; McNeill, J. Photosensitizer-doped conjugated polymer nanoparticles with high cross-sections for one- and two-photon excitation. Nanoscale 2011, 3, 1451-1455.
[62] Shen, X.; Li, L.; Wu, H.; Yao, S. Q.; Xu, Q.-H. Photosensitizer-doped conjugated polymer nanoparticles for simultaneous two-photon imaging and two-photon photodynamic therapy in living cells. Nanoscale 2011, 3, 5140-5146.
[63] Zhang, Y.; Pang, L.; Ma, C.; Tu, Q.; Zhang, R.; Saeed, E.; Mahmoud, A. E.; Wang, J. Small Molecule-Initiated Light-Activated Semiconducting Polymer Dots: An Integrated Nanoplatform for Targeted Photodynamic Therapy and Imaging of Cancer Cells. Analytical Chemistry 2014, 86, 3092-3099.
[64] Feng, Z. Y.; Tao, P.; Zou, L.; Gao, P. L.; Liu, Y.; Liu, X.; Wang, H.; Liu, S. J.; Dong, Q. C.; Li, J.; Xu, B. S.; Huang, W.; Wong, W. Y.; Zhao, Q. Hyperbranched Phosphorescent Conjugated Polymer Dots with Iridium(III) Complex as the Core for Hypoxia Imaging and Photodynamic Therapy. ACS Appl. Mater. Interfaces 2017, 9, 28319-28330.
[65] Yang, T.; Liu, L.; Deng, Y. B.; Guo, Z. Q.; Zhang, G. B.; Ge, Z. S.; Ke, H. T.; Chen, H. B. Ultrastable Near-Infrared Conjugated-Polymer Nanoparticles for Dually Photoactive Tumor Inhibition. Adv. Mater. 2017, 29, 9.
[66] Kim, C.; Kim, S. Y.; Lim, Y. T.; Lee, T. S. Synthesis of conjugated polymer nanoparticles with core-shell structure for cell imaging and photodynamic cancer therapy. Macromol. Res. 2017, 25, 572-577.
[67] Feng, G.; Fang, Y.; Liu, J.; Geng, J.; Ding, D.; Liu, B. Multifunctional Conjugated Polymer Nanoparticles for Image-Guided Photodynamic and Photothermal Therapy. Small 2017, 13, 12.
[68] Haupt, S.; Lazar, I.; Weitman, H.; Shav-Tal, Y.; Ehrenberg, B. FRET energy transfer via Pdots improves the efficiency of photodynamic therapy and leads to rapid cell death. J. Photochem. Photobiol. B-Biol. 2016, 164, 123-131.
[69] Zhou, X. B.; Liang, H.; Jiang, P. F.; Zhang, K. Y.; Liu, S. J.; Yang, T. S.; Zhao, Q.; Yang, L. J.; Lv, W.; Yu, Q.; Huang, W. Multifunctional Phosphorescent Conjugated Polymer Dots for Hypoxia Imaging and Photodynamic Therapy of Cancer Cells. Adv. Sci. 2016, 3, 12.
[70] Shen, X. Q.; Li, S.; Li, L.; Yao, S. Q.; Xu, Q. H. Highly Efficient, Conjugated-Polymer-Based Nano-Photosensitizers for Selectively Targeted Two-Photon Photodynamic Therapy and Imaging of Cancer Cells. Chem.-Eur. J. 2015, 21, 2214-2221.
[71] Hu, Z.; Gesquiere, A. J. PCBM concentration dependent morphology of P3HT in composite P3HT/PCBM nanoparticles. Chemical Physics Letters 2009, 476, 51-55.
[72] Hu, Z.; Gesquiere, A. J. Charge Trapping and Storage by Composite P3HT/PC60BM Nanoparticles Investigated by Fluorescence-Voltage/Single Particle Spectroscopy. J. Am. Chem. Soc. 2011, 133, 20850-20856.
[73] Hu, Z.; Tenery, D.; Bonner, M. S.; Gesquiere, A. J. Correlation between spectroscopic and morphological properties of composite P3HT/PCBM nanoparticles studied by single particle spectroscopy. Journal of Luminescence 2010, 130, 771-780.
[74] Tenery, D.; Gesquiere, A. J. Effect of PCBM Concentration on Photoluminescence Properties of Composite MEH-PPV/PCBM Nanoparticles Investigated by a Franck-Condon Analysis of Single-Particle Emission Spectra. Chemphyschem 2009, 10, 2449-2457.
[75] Tenery, D.; Gesquiere, A. J. Interplay between fluorescence and morphology in composite MEH-PPV/PCBM nanoparticles studied at the single particle level. Chemical Physics 2009, 365, 138-143.
[76] Tenery, D.; Worden, J. G.; Hu, Z.; Gesquiere, A. J. Single particle spectroscopy on composite MEH-PPV/PCBM nanoparticles. Journal of Luminescence 2009, 129, 423-429.
[77] Yu, J.; Lammi, R.; Gesquiere, A. J.; Barbara, P. F. Singlet-triplet and triplet-triplet interactions in conjugated polymer single molecules. Journal of Physical Chemistry B 2005, 109, 10025-10034.
[78] Wu, C.; Hansen, S. J.; Hou, Q.; Yu, J.; Zeigler, M.; Jin, Y.; Burnham, D. R.; McNeill, J. D.; Olson, J. M.; Chiu, D. T. Design of Highly Emissive Polymer Dot Bioconjugates for In Vivo Tumor Targeting. Angewandte Chemie-International Edition 2011, 50, 3430-3434.
[79] Sariciftci, N. S.; Smilowitz, L.; Heeger, A. J.; Wudl, F. Photoinduced electron transfer from a conducting polymer to buckminsterfullerene. Science 1992, 258, 1474-1476.
[80] Sperandio, F. F.; Sharma, S. K.; Wang, M.; Jeon, S.; Huang, Y. Y.; Dai, T. H.; Nayka, S.; de Sousa, S.; Chiang, L. Y.; Hamblin, M. R. Photoinduced electron-transfer mechanisms for radical-enhanced photodynamic therapy mediated by water-soluble decacationic C-70 and C84O2 Fullerene Derivatives. Nanomed.-Nanotechnol. Biol. Med. 2013, 9, 570-579.
[81] Fan, J. Q.; Fang, G.; Zeng, F.; Wang, X. D.; Wu, S. Z. Water-Dispersible Fullerene Aggregates as a Targeted Anticancer Prodrug with both Chemo- and Photodynamic Therapeutic Actions. Small 2013, 9, 613-621.
[82] Grynyuk, I.; Grebinyk, S.; Prylutska, S.; Mykhailova, A.; Franskevich, D.; Matyshevska, O.; Schutze, C.; Ritter, U. Photoexcited fullerene C-60 disturbs prooxidant-antioxidant balance in leukemic L1210 cells. Materialwiss. Werkstofftech. 2013, 44, 139-143.
[83] 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-C-60 nanoplatform for NIR imaging-guided photodynamic therapy of cancer cells. Chem. Commun. 2013, 49, 3224-3226.
[84] Trpkovic, A.; Todorovic-Markovic, B.; Trajkovic, V. Toxicity of pristine versus functionalized fullerenes: mechanisms of cell damage and the role of oxidative stress. Arch. Toxicol. 2012, 86, 1809-1827.
[85] Chen, Z. Y.; Ma, L. J.; Liu, Y.; Chen, C. Y. Applications of Functionalized Fullerenes in Tumor Theranostics. Theranostics 2012, 2, 238-250.
[86] Gao, H. J.; Shi, W. D.; Freund, L. B. Mechanics of receptor-mediated endocytosis. Proc. Natl. Acad. Sci. U. S. A. 2005, 102, 9469-9474.
[87] Lerch, S.; Dass, M.; Musyanovych, A.; Landfester, K.; Mailander, V. Polymeric nanoparticles of different sizes overcome the cell membrane barrier. Eur. J. Pharm. Biopharm. 2013, 84, 265-274.
[88] Tang, L.; Gabrielson, N. P.; Uckun, F. M.; Fan, T. M.; Cheng, J. J. Size-Dependent Tumor Penetration and in Vivo Efficacy of Monodisperse Drug-Silica Nanoconjugates. Molecular Pharmaceutics 2013, 10, 883-892.
[89] Park, S. H.; Roy, A.; Beaupré, S.; Cho, S.; Coates, N.; Moon, J. S.; Moses, D.; Leclerc, M.; Lee, K.; Heeger, A. J. Bulk heterojunction solar cells with internal quantum efficiency approaching 100%. Nature Photonics 2009, 3, 297-302.
[90] Doshi, M.; Treglown, K.; Copik, A.; Gesquiere, A. J. Composite Conjugated Polymer/Fullerene Nanoparticles as Sensitizers in Photodynamic Therapy for Cancer. BioNanoScience 2014, 4, 15-26.
[91] Ross, J. F.; Chaudhuri, P. K.; Ratnam, M. Differential regulation of folate receptor isoforms in normal and malignant tissues in vivo and in established cell lines. Physiologic and clinical implications. Cancer 1994, 73, 2432-2443.
[92] Parker, N.; Turk, M. J.; Westrick, E.; Lewis, J. D.; Low, P. S.; Leamon, C. P. Folate receptor expression in carcinomas and normal tissues determined by a quantitative radioligand binding assay. Analytical Biochemistry 2005, 338, 284-293.
[93] Zhang, Y.; Yang, M.; Portney, N. G.; Cui, D. X.; Budak, G.; Ozbay, E.; Ozkan, M.; Ozkan, C. S. Zeta potential: a surface electrical characteristic to probe the interaction of nanoparticles with normal and cancer human breast epithelial cells. Biomed. Microdevices 2008, 10, 321-328.
[94] Gratton, S. E. A.; Ropp, P. A.; Pohlhaus, P. D.; Luft, J. C.; Madden, V. J.; Napier, M. E.; DeSimone, J. M. The effect of particle design on cellular internalization pathways. Proc. Natl. Acad. Sci. U. S. A. 2008, 105, 11613-11618.
[95] Huhn, D.; Kantner, K.; Geidel, C.; Brandholt, S.; De Cock, I.; Soenen, S. J. H.; Gil, P. R.; Montenegro, J. M.; Braeckmans, K.; Mullen, K.; Nienhaus, G. U.; Klapper, M.; Parak, W. J. Polymer-Coated Nanoparticles Interacting with Proteins and Cells: Focusing on the Sign of the Net Charge. ACS Nano 2013, 7, 3253-3263.
[96] Xu, P. S.; Van Kirk, E. A.; Zhan, Y. H.; Murdoch, W. J.; Radosz, M.; Shen, Y. Q. Targeted charge-reversal nanoparticles for nuclear drug delivery. Angewandte Chemie-International Edition 2007, 46, 4999-5002.
[97] Valko, M.; Rhodes, C. J.; Moncol, J.; Izakovic, M.; Mazur, M. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem.-Biol. Interact. 2006, 160, 1-40.
[98] Toffoli, G.; Cernigoi, C.; Russo, A.; Gallo, A.; Bagnoli, M.; Boiocchi, M. Overexpression of folate binding protein in ovarian cancers. Int. J. Cancer 1997, 74, 193-198.
[99] Schumacker, P. T. Reactive oxygen species in cancer cells: Live by the sword, die by the sword. Cancer Cell 2006, 10, 175-176.
[100] Lee, J.; Twomey, M.; Machado, C.; Gomez, G.; Doshi, M.; Gesquiere, A. J.; Moon, J. H. Caveolae-Mediated Endocytosis of Conjugated Polymer Nanoparticles. Macromolecular Bioscience 2013, 13, 913-920.
[101] Kim, J.-S.; Yoon, T.-J.; Yu, K.-N.; Noh, M. S.; Woo, M.; Kim, B.-G.; Lee, K.-H.; Sohn, B.-H.; Park, S.-B.; Lee, J.-K.; Cho, M.-H. Cellular uptake of magnetic nanoparticle is mediated through energy-dependent endocytosis in A549 cells. J Vet Sci 2006, 7, 321-326.
[102] Fretz, M. M.; Koning, G. A.; Mastrobattista, A.; Jiskoot, W.; Storm, G. OVCAR-3 cells internalize TAT-peptide modified liposomes by endocytosis. Biochimica Et Biophysica Acta-Biomembranes 2004, 1665, 48-56.
[103] Doshi, M.; Copik, A.; Gesquiere, A. J. Development and characterization of conducting polymer nanoparticles for photodynamic therapy in vitro. Photodiagnosis and Photodynamic Therapy 2015, 12, 476-489.
[104] Houle, J.-M.; Strong, H. A. Duration of Skin Photosensitivity and Incidence of Photosensitivity Reactions After Administration of Verteporfin. RETINA 2002, 22, 691-697.
[105] Moriwaki, S.-I.; Misawa, J.; Yoshinari, Y.; Yamada, I.; Takigawa, M.; Tokura, Y. Analysis of photosensitivity in Japanese cancer-bearing patients receiving photodynamic therapy with porfimer sodium (PhotofrinTM). Photodermatology, Photoimmunology & Photomedicine 2001, 17, 241-243.
[106] van Dongen, G. A. M. S.; Visser, G. W. M.; Vrouenraets, M. B. Photosensitizer-antibody conjugates for detection and therapy of cancer. Adv. Drug Deliv. Rev. 2004, 56, 31-52.
[107] Weitman, S. D.; Lark, R. H.; Coney, L. R.; Fort, D. W.; Frasca, V.; Zurawski, V. R.; Kamen, B. A. Distribution of the Folate Receptor GP38 in Normal and Malignant Cell Lines and Tissues. Cancer Research 1992, 52, 3396-3401.
[108] Real, F. X.; Rettig, W. J.; Chesa, P. G.; Melamed, M. R.; Old, L. J.; Mendelsohn, J. Expression of Epidermal Growth Factor Receptor in Human Cultured Cells and Tissues: Relationship to Cell Lineage and Stage of Differentiation. Cancer Research 1986, 46, 4726-4731.
[109] Ahmed, N.; Salsman, V. S.; Yvon, E.; Louis, C. U.; Perlaky, L.; Wels, W. S.; Dishop, M. K.; Kleinerman, E. E.; Pule, M.; Rooney, C. M.; Heslop, H. E.; Gottschalk, S. Immunotherapy for Osteosarcoma: Genetic Modification of T cells Overcomes Low Levels of Tumor Antigen Expression. Mol Ther 2009, 17, 1779-1787.
[110] Subik, K.; Lee, J.-F.; Baxter, L.; Strzepek, T.; Costello, D.; Crowley, P.; Xing, L.; Hung, M.-C.; Bonfiglio, T.; Hicks, D. G.; Tang, P. The Expression Patterns of ER, PR, HER2, CK5/6, EGFR, Ki-67 and AR by Immunohistochemical Analysis in Breast Cancer Cell Lines. Breast Cancer: Basic and Clinical Research 2010, 4, 35-41.
[111] Doshi, M.; Krienke, M.; Khederzadeh, S.; Sanchez, H.; Copik, A.; Oyer, J.; Gesquiere, A. J. Conducting polymer nanoparticles for targeted cancer therapy. RSC Advances 2015, 5, 37943-37956.
[112] Antony, A. C. Folate Receptors. Annual Review of Nutrition 1996, 16, 501-521.
[113] Campbell, I. G.; Jones, T. A.; Foulkes, W. D.; Trowsdale, J. Folate-binding Protein Is a Marker for Ovarian Cancer. Cancer Research 1991, 51, 5329-5338.
[114] Sudimack, J.; Lee, R. J. Targeted drug delivery via the folate receptor. Adv. Drug Deliv. Rev. 2000, 41, 147-162.
[115] Scarano, W.; Duong, H. T. T.; Lu, H.; De Souza, P. L.; Stenzel, M. H. Folate Conjugation to Polymeric Micelles via Boronic Acid Ester to Deliver Platinum Drugs to Ovarian Cancer Cell Lines. Biomacromolecules 2013, 14, 962-975.
[116] Garinchesa, P. C., I. ;Saigo, P. E. ;Lewis, J. L. ;Old, L. J. ;Rettig, W. J. . Trophoblast and Ovarian-Cancer Antigen-LK26 -Sensitivity and Specificity in Immunopathology and Molecular-Identification as a Folate-Binding Protein. American Journal of Pathology 1993, 142, 557-567.
[117] Bharali, D. J.; Lucey, D. W.; Jayakumar, H.; Pudavar, H. E.; Prasad, P. N. Folate-Receptor-Mediated Delivery of InP Quantum Dots for Bioimaging Using Confocal and Two-Photon Microscopy. J. Am. Chem. Soc. 2005, 127, 11364-11371.
[118] Choi, H.; Choi, S. R.; Zhou, R.; Kung, H. F.; Chen, I. W. Iron oxide nanoparticles as magnetic resonance contrast agent for tumor imaging via folate receptor-targeted delivery1. Academic Radiology 2004, 11, 996-1004.
[119] Hwa Kim, S.; Hoon Jeong, J.; Joe, C. O.; Gwan Park, T. Folate receptor mediated intracellular protein delivery using PLL-PEG-FOL conjugate. Journal of Controlled Release 2005, 103, 625-634.
[120] Koyakutty, M.; Seby, J.; Deepa, T.; Sonali, S.; Deepthy, M.; Shantikumar, N. Bio-conjugated luminescent quantum dots of doped ZnS: a cyto-friendly system for targeted cancer imaging. Nanotechnology 2009, 20, 065102.
[121] Lee, D.; Lockey, R.; Mohapatra, S. Folate Receptor-Mediated Cancer Cell Specific Gene Delivery Using Folic Acid-Conjugated Oligochitosans. Journal of Nanoscience and Nanotechnology 2006, 6, 2860-2866.
[122] Doshi, M.; Treglown, K.; Copik, A.; Gesquiere, A. Composite Conjugated Polymer/Fullerene Nanoparticles as Sensitizers in Photodynamic Therapy for Cancer. BioNanoScience 2014, 4, 15-26.
[123] Setua, S.; Menon, D.; Asok, A.; Nair, S.; Koyakutty, M. Folate receptor targeted, rare-earth oxide nanocrystals for bi-modal fluorescence and magnetic imaging of cancer cells. Biomaterials 2010, 31, 714-729.
[124] Tavassolian, F.; Kamalinia, G.; Rouhani, H.; Amini, M.; Ostad, S. N.; Khoshayand, M. R.; Atyabi, F.; Tehrani, M. R.; Dinarvand, R. Targeted poly (L-Y-glutamyl glutamine) nanoparticles of docetaxel against folate over-expressed breast cancer cells. International Journal of Pharmaceutics 2014, 467, 123-138.
[125] Yoo, H. S.; Park, T. G. Folate-receptor-targeted delivery of doxorubicin nano-aggregates stabilized by doxorubicin-PEG-folate conjugate. Journal of Controlled Release 2004, 100, 247-256.