Cathepsin B-degradable, NIR-responsive nanoparticulate platform for target-specific cancer therapy

Sam P Tarassoli, Alejandra Martinez de Pinillos Bayona, Hayley Pye, C. Alexander Mosse, J Callan, Alexander MacRobert, AP McHale, Nikolitsa Nomikou

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Stimuli-responsive anticancer formulations can promote drug release and activation within the target tumour, facilitate cellular uptake, as well as improve the therapeutic efficacy of drugs and reduce off-target effects. In the present work, indocyanine green (ICG)-containing polyglutamate (PGA) nanoparticles were developed and characterized. Digestion of nanoparticles with cathepsin B, a matrix metalloproteinase overexpressed in the microenvironment of advanced tumours, decreased particle size and increased ICG cellular uptake. Incorporation of ICG in PGA nanoparticles provided the NIR-absorbing agent with time-dependent altered optical properties in the presence of cathepsin B. Having minimal dark toxicity, the formulation exhibited significant cytotoxicity upon NIR exposure. Combined use of the formulation with saporin, a ribosome-inactivating protein, resulted in synergistically enhanced cytotoxicity attributed to the photo-induced release of saporin from endo/lysosomes. The results suggest that this therapeutic approach can offer significant therapeutic benefit in the treatment of superficial malignancies, such as head and neck tumours.
LanguageEnglish
JournalNanotechnology
Volume28
Issue number5
Early online date28 Dec 2016
DOIs
Publication statusPublished - 3 Feb 2017

Fingerprint

Cathepsin B
Indocyanine Green
Nanoparticles
Polyglutamic Acid
Ribosome Inactivating Proteins
Neoplasms
Tumor Microenvironment
Lysosomes
Matrix Metalloproteinases
Particle Size
Digestion
Neck
Therapeutics
Head
Pharmaceutical Preparations
saporin

Keywords

  • indocyanine green
  • polyglutamate
  • cathepsin B
  • near infra-red
  • laser cancer treatment

Cite this

Tarassoli, S. P., Martinez de Pinillos Bayona, A., Pye, H., Mosse, C. A., Callan, J., MacRobert, A., ... Nomikou, N. (2017). Cathepsin B-degradable, NIR-responsive nanoparticulate platform for target-specific cancer therapy. Nanotechnology, 28(5). https://doi.org/10.1088/1361-6528/28/5/055101
Tarassoli, Sam P ; Martinez de Pinillos Bayona, Alejandra ; Pye, Hayley ; Mosse, C. Alexander ; Callan, J ; MacRobert, Alexander ; McHale, AP ; Nomikou, Nikolitsa. / Cathepsin B-degradable, NIR-responsive nanoparticulate platform for target-specific cancer therapy. In: Nanotechnology. 2017 ; Vol. 28, No. 5.
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title = "Cathepsin B-degradable, NIR-responsive nanoparticulate platform for target-specific cancer therapy",
abstract = "Stimuli-responsive anticancer formulations can promote drug release and activation within the target tumour, facilitate cellular uptake, as well as improve the therapeutic efficacy of drugs and reduce off-target effects. In the present work, indocyanine green (ICG)-containing polyglutamate (PGA) nanoparticles were developed and characterized. Digestion of nanoparticles with cathepsin B, a matrix metalloproteinase overexpressed in the microenvironment of advanced tumours, decreased particle size and increased ICG cellular uptake. Incorporation of ICG in PGA nanoparticles provided the NIR-absorbing agent with time-dependent altered optical properties in the presence of cathepsin B. Having minimal dark toxicity, the formulation exhibited significant cytotoxicity upon NIR exposure. Combined use of the formulation with saporin, a ribosome-inactivating protein, resulted in synergistically enhanced cytotoxicity attributed to the photo-induced release of saporin from endo/lysosomes. The results suggest that this therapeutic approach can offer significant therapeutic benefit in the treatment of superficial malignancies, such as head and neck tumours.",
keywords = "indocyanine green, polyglutamate, cathepsin B, near infra-red, laser cancer treatment",
author = "Tarassoli, {Sam P} and {Martinez de Pinillos Bayona}, Alejandra and Hayley Pye and Mosse, {C. Alexander} and J Callan and Alexander MacRobert and AP McHale and Nikolitsa Nomikou",
note = "Reference text: [1] Du J, Lane LA, Nie S. Stimuli-responsive nanoparticles for targeting the tumor microenvironment. J Control Release 2015;219:205-14. [2] Webb BA, Chimenti M, Jacobson MP, Barber DL. Dysregulated pH: a perfect storm for cancer progression. Nat Rev Cancer 2011;11:671-7. [3] Maeda H, Nakamura H, Fang J. The EPR effect for macromolecular drug delivery to solid tumors: Improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo. Adv Drug Deliv Rev 2013;65:71-9. [4] de la Rica R, Aili D, Stevens MM. Enzyme-responsive nanoparticles for drug release and diagnostics. Adv Drug Deliv Rev 2012;64:967-78. [5] Brown JM, Wilson WR. Exploiting tumour hypoxia in cancer treatment. Nat Rev Cancer 2004;4:437-47. [6] Akhtar MJ, Ahamed M, Alhadlaq HA, Alrokayan SA, Kumar S. Targeted anticancer therapy: overexpressed receptors and nanotechnology. Clin Chim Acta 2014;436:78-92. [7] Chipman SD, Oldham FB, Pezzoni G, Singer JW. Biological and clinical characterization of paclitaxel poliglumex (PPX, CT-2103), a macromolecular polymer-drug conjugate. Int J Nanomedicine 2006;1:375-83. [8] Roshy S, Sloane BF, Moin K. Pericellular cathepsin B and malignant progression. Cancer Metastasis Rev 2003;22:271-86. [9] Li C, Newman RA, Wu QP, Ke S, Chen W, Hutto T, et al. Biodistribution of paclitaxel and poly(L-glutamic acid)-paclitaxel conjugate in mice with ovarian OCa-1 tumor. Cancer Chemother Pharmacol 2000;46:416-22. [10] Homsi J, Simon GR, Garrett CR, Springett G, De Conti R, Chiappori AA, et al. Phase I trial of poly-L-glutamate camptothecin (CT-2106) administered weekly in patients with advanced solid malignancies. Clin Cancer Res 2007;13:5855-61. [11] Singer JW, Shaffer S, Baker B, Bernareggi A, Stromatt S, Nienstedt D, et al. Paclitaxel poliglumex (XYOTAX; CT-2103): an intracellularly targeted taxane. Anticancer Drugs 2005;16:243-54. [12] Dolmans DE, Fukumura D, Jain RK. Photodynamic therapy for cancer. Nat Rev Cancer 2003;3:380-7. [13] Andrzejak M, Santiago M, Kessel D. Effects of endosomal photodamage on membrane recycling and endocytosis. Photochem Photobiol 2011;87:699-706. [14] Norum OJ, Selbo PK, Weyergang A, Giercksky KE, Berg K. Photochemical internalization (PCI) in cancer therapy: from bench towards bedside medicine. J Photochem Photobiol B 2009;96:83-92. [15] Kim H, Lee D, Kim J, Kim TI, Kim WJ. Photothermally triggered cytosolic drug delivery via endosome disruption using a functionalized reduced graphene oxide. ACS Nano 2013;7:6735-46. [16] Zhao P, Zheng M, Luo Z, Gong P, Gao G, Sheng Z, et al. NIR-driven Smart Theranostic Nanomedicine for On-demand Drug Release and Synergistic Antitumour Therapy. Sci Rep 2015;5:14258. [17] Weissleder R. A clearer vision for in vivo imaging. Nat Biotechnol 2001;19:316-7. [18] Gazouli M, Nomikou N, Callan JF, Efstathopoulos EP. Novel nanotechnology approaches for targeted cancer therapy. Curr Nanomed 2016;3(2):83-8. [19] Baumler W, Abels C, Karrer S, Weiss T, Messmann H, Landthaler M, et al. Photo-oxidative killing of human colonic cancer cells using indocyanine green and infrared light. Br J Cancer 1999;80:360-3. [20] Yan L, Qiu L. Indocyanine green targeted micelles with improved stability for near-infrared image-guided photothermal tumor therapy. Nanomedicine (Lond) 2015;10:361-73. [21] Nomikou N, Sterrett C, Arthur C, McCaughan B, Callan JF, McHale AP. The effects of ultrasound and light on indocyanine-green-treated tumour cells and tissues. ChemMedChem 2012;7:1465-71. [22] Ott P. Hepatic elimination of indocyanine green with special reference to distribution kinetics and the influence of plasma protein binding. Pharmacol Toxicol 1998;83(2):1-48. [23] Zheng X, Xing D, Zhou F, Wu B, Chen WR. Indocyanine green-containing nanostructure as near infrared dual-functional targeting probes for optical imaging and photothermal therapy. Mol Pharm 2011;8:447-56. [24] Zheng M, Yue C, Ma Y, Gong P, Zhao P, Zheng C, et al. Single-step assembly of DOX/ICG loaded lipid--polymer nanoparticles for highly effective chemo-photothermal combination therapy. ACS Nano 2013;7:2056-67. [25] Wan Z, Mao H, Guo M, Li Y, Zhu A, Yang H, et al. Highly efficient hierarchical micelles integrating photothermal therapy and singlet oxygen-synergized chemotherapy for cancer eradication. Theranostics 2014;4:399-411. [26] Yamaguchi F, Ogawa Y, Kikuchi M, Yuasa K, Motai H. Detection of gamma-Polyglutamic Acid (gamma-PGA) by SDS-Page. Biosci Biotechnol Biochem 1996;60:255-8. [27] Zia Q, Khan AA, Swaleha Z, Owais M. Self-assembled amphotericin B-loaded polyglutamic acid nanoparticles: preparation, characterization and in vitro potential against Candida albicans. Int J Nanomedicine 2015;10:1769-90. [28] Beziere N, Lozano N, Nunes A, Salichs J, Queiros D, Kostarelos K, Ntziachristos V. Dynamic imaging of PEGylated indocyanine green (ICG) liposomes within the tumor microenvironment using multi-spectral optoacoustic tomography (MSOT). Biomaterials 2015;37:415-24. [29] Rajian JR, Fabiilli ML, Fowlkes JB, Carson PL, Wang X. Drug delivery monitoring by photoacoustic tomography with an ICG encapsulated double emulsion. Opt Express 2011;19(15):14335-47. [30] Weigand R, Rotermund F, Penzkofer A. Aggregation dependent absorption reduction of indocyanine green. ‎J Phys Chem A 1997;101:7729-34. [31] Awasthi K, Nishimura G. Modification of near-infrared cyanine dyes by serum albumin protein. Photochem Photobiol Sci 2011;10:461-3. [32] Kirchherr AK, Briel A, Mader K. Stabilization of indocyanine green by encapsulation within micellar systems. Mol Pharm 2009;6:480-91. [33] Ng KK, Zheng G. Molecular interactions in organic nanoparticles for phototheranostic applications. Chem Rev 2015;115:11012-42. [34] Mordon S, Devoisselle JM, Soulie-Begu S, Desmettre T. Indocyanine green: physicochemical factors affecting its fluorescence in vivo. Microvasc Res 1998;55:146-52. [35] Kelkar SS, Hill TK, Marini FC, Mohs AM. Near infrared fluorescent nanoparticles based on hyaluronic acid: Self-assembly, optical properties, and cell interaction. Acta Biomater 2016;36:112-21. [36] Weng A, Manunta MD, Thakur M, Gilabert-Oriol R, Tagalakis AD, Eddaoudi A, Munye MM, Vink CA, Wiesner B, Eichhorst J, Melzig MF, Hart SL. Improved intracellular delivery of peptide- and lipid-nanoplexes by natural glycosides. J Control Release 2015;206:75-90. [37] Allen TM, Cullis PR. Drug delivery systems: entering the mainstream. Science 2004;303:1818-22. [38] Cabral H, Matsumoto Y, Mizuno K, Chen Q, Murakami M, Kimura M, et al. Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size. Nat Nanotechnol 2011;6:815-23. [39] Wong C, Stylianopoulos T, Cui J, Martin J, Chauhan VP, Jiang W, et al. Multistage nanoparticle delivery system for deep penetration into tumor tissue. Proc Natl Acad Sci U S A 2011;108:2426-31. [40] Choi HS, Liu W, Liu F, Nasr K, Misra P, Bawendi MG, et al. Design considerations for tumour-targeted nanoparticles. Nat Nanotechnol 2010;5:42-7. [41] Choi HS, Liu W, Misra P, Tanaka E, Zimmer JP, Itty Ipe B, et al. Renal clearance of quantum dots. Nat Biotechnol 2007;25:1165-70. [42] Mansour AM, Drevs J, Esser N, Hamada FM, Badary OA, Unger C, et al. A new approach for the treatment of malignant melanoma: enhanced antitumor efficacy of an albumin-binding doxorubicin prodrug that is cleaved by matrix metalloproteinase 2. Cancer Res 2003;63:4062-6. [43] Lee GY, Park K, Kim SY, Byun Y. MMPs-specific PEGylated peptide-DOX conjugate micelles that can contain free doxorubicin. Eur J Pharm Biopharm 2007;67:646-54. [44] Chen WH, Luo GF, Lei Q, Jia HZ, Hong S, Wang QR, et al. MMP-2 responsive polymeric micelles for cancer-targeted intracellular drug delivery. Chem Commun (Camb) 2015;51:465-8. [45] Jian WH, Yu TW, Chen CJ, Huang WC, Chiu HC, Chiang WH. Indocyanine green-encapsulated hybrid polymeric nanomicelles for photothermal cancer therapy. Langmuir 2015;31:6202-10. [46] Kawasaki G, Kato Y, Mizuno A. Cathepsin expression in oral squamous cell carcinoma: relationship with clinicopathologic factors. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;93:446-54. [47] Keereweer S, Mol IM, Kerrebijn JD, Van Driel PB, Xie B, Baatenburg de Jong RJ, et al. Targeting integrins and enhanced permeability and retention (EPR) effect for optical imaging of oral cancer. J Surg Oncol 2012;105:714-8. [48] Ochs, M.;Carregal-Romero, S.;Rejman, J.;Braeckmans, K.;De Smedt, S. C.; Parak, W. J. Light-addressable capsules as caged compound matrix for controlled triggering of cytosolic reactions. Angew. Chem. Int. Ed. Engl. 2013, 52, 695-699. [49] Zhu B, Li Y, Lin Z, Zhao M, Xu T, Wang C, Deng N. Silver nanoparticles induce HePG-2 cells apoptosis through ROS-mediated signaling pathways. Nanoscale Res Lett 2016;11(1):198. [50] Zhang Z, Wang J, Chen C. Near-Infrared light-mediated nanoplatforms for cancer thermo-chemotherapy and optical imaging. Adv Mater 2013;25(28):3869-80 [51] Berg K, Selbo PK, Prasmickaite L, Tjelle TE, Sandvig K, Moan J, et al. Photochemical internalization: a novel technology for delivery of macromolecules into cytosol. Cancer Res 1999;59:1180-3. [52] Philip R, Penzkofer A, B{\"a}umler W, Szeimies RM, Abels C. Absorption and fluorescence spectroscopic investigation of indocyanine green. J Photochem Photobiol A Chem 1996;96:137-48.",
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Tarassoli, SP, Martinez de Pinillos Bayona, A, Pye, H, Mosse, CA, Callan, J, MacRobert, A, McHale, AP & Nomikou, N 2017, 'Cathepsin B-degradable, NIR-responsive nanoparticulate platform for target-specific cancer therapy', Nanotechnology, vol. 28, no. 5. https://doi.org/10.1088/1361-6528/28/5/055101

Cathepsin B-degradable, NIR-responsive nanoparticulate platform for target-specific cancer therapy. / Tarassoli, Sam P; Martinez de Pinillos Bayona, Alejandra; Pye, Hayley; Mosse, C. Alexander; Callan, J; MacRobert, Alexander; McHale, AP; Nomikou, Nikolitsa.

In: Nanotechnology, Vol. 28, No. 5, 03.02.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cathepsin B-degradable, NIR-responsive nanoparticulate platform for target-specific cancer therapy

AU - Tarassoli, Sam P

AU - Martinez de Pinillos Bayona, Alejandra

AU - Pye, Hayley

AU - Mosse, C. Alexander

AU - Callan, J

AU - MacRobert, Alexander

AU - McHale, AP

AU - Nomikou, Nikolitsa

N1 - Reference text: [1] Du J, Lane LA, Nie S. Stimuli-responsive nanoparticles for targeting the tumor microenvironment. J Control Release 2015;219:205-14. [2] Webb BA, Chimenti M, Jacobson MP, Barber DL. Dysregulated pH: a perfect storm for cancer progression. Nat Rev Cancer 2011;11:671-7. [3] Maeda H, Nakamura H, Fang J. The EPR effect for macromolecular drug delivery to solid tumors: Improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo. Adv Drug Deliv Rev 2013;65:71-9. [4] de la Rica R, Aili D, Stevens MM. Enzyme-responsive nanoparticles for drug release and diagnostics. Adv Drug Deliv Rev 2012;64:967-78. [5] Brown JM, Wilson WR. Exploiting tumour hypoxia in cancer treatment. Nat Rev Cancer 2004;4:437-47. [6] Akhtar MJ, Ahamed M, Alhadlaq HA, Alrokayan SA, Kumar S. Targeted anticancer therapy: overexpressed receptors and nanotechnology. Clin Chim Acta 2014;436:78-92. [7] Chipman SD, Oldham FB, Pezzoni G, Singer JW. Biological and clinical characterization of paclitaxel poliglumex (PPX, CT-2103), a macromolecular polymer-drug conjugate. Int J Nanomedicine 2006;1:375-83. [8] Roshy S, Sloane BF, Moin K. Pericellular cathepsin B and malignant progression. Cancer Metastasis Rev 2003;22:271-86. [9] Li C, Newman RA, Wu QP, Ke S, Chen W, Hutto T, et al. Biodistribution of paclitaxel and poly(L-glutamic acid)-paclitaxel conjugate in mice with ovarian OCa-1 tumor. Cancer Chemother Pharmacol 2000;46:416-22. [10] Homsi J, Simon GR, Garrett CR, Springett G, De Conti R, Chiappori AA, et al. Phase I trial of poly-L-glutamate camptothecin (CT-2106) administered weekly in patients with advanced solid malignancies. Clin Cancer Res 2007;13:5855-61. [11] Singer JW, Shaffer S, Baker B, Bernareggi A, Stromatt S, Nienstedt D, et al. Paclitaxel poliglumex (XYOTAX; CT-2103): an intracellularly targeted taxane. Anticancer Drugs 2005;16:243-54. [12] Dolmans DE, Fukumura D, Jain RK. Photodynamic therapy for cancer. Nat Rev Cancer 2003;3:380-7. [13] Andrzejak M, Santiago M, Kessel D. Effects of endosomal photodamage on membrane recycling and endocytosis. Photochem Photobiol 2011;87:699-706. [14] Norum OJ, Selbo PK, Weyergang A, Giercksky KE, Berg K. Photochemical internalization (PCI) in cancer therapy: from bench towards bedside medicine. J Photochem Photobiol B 2009;96:83-92. [15] Kim H, Lee D, Kim J, Kim TI, Kim WJ. Photothermally triggered cytosolic drug delivery via endosome disruption using a functionalized reduced graphene oxide. ACS Nano 2013;7:6735-46. [16] Zhao P, Zheng M, Luo Z, Gong P, Gao G, Sheng Z, et al. NIR-driven Smart Theranostic Nanomedicine for On-demand Drug Release and Synergistic Antitumour Therapy. Sci Rep 2015;5:14258. [17] Weissleder R. A clearer vision for in vivo imaging. Nat Biotechnol 2001;19:316-7. [18] Gazouli M, Nomikou N, Callan JF, Efstathopoulos EP. Novel nanotechnology approaches for targeted cancer therapy. Curr Nanomed 2016;3(2):83-8. [19] Baumler W, Abels C, Karrer S, Weiss T, Messmann H, Landthaler M, et al. Photo-oxidative killing of human colonic cancer cells using indocyanine green and infrared light. Br J Cancer 1999;80:360-3. [20] Yan L, Qiu L. Indocyanine green targeted micelles with improved stability for near-infrared image-guided photothermal tumor therapy. Nanomedicine (Lond) 2015;10:361-73. [21] Nomikou N, Sterrett C, Arthur C, McCaughan B, Callan JF, McHale AP. The effects of ultrasound and light on indocyanine-green-treated tumour cells and tissues. ChemMedChem 2012;7:1465-71. [22] Ott P. Hepatic elimination of indocyanine green with special reference to distribution kinetics and the influence of plasma protein binding. Pharmacol Toxicol 1998;83(2):1-48. [23] Zheng X, Xing D, Zhou F, Wu B, Chen WR. Indocyanine green-containing nanostructure as near infrared dual-functional targeting probes for optical imaging and photothermal therapy. Mol Pharm 2011;8:447-56. [24] Zheng M, Yue C, Ma Y, Gong P, Zhao P, Zheng C, et al. Single-step assembly of DOX/ICG loaded lipid--polymer nanoparticles for highly effective chemo-photothermal combination therapy. ACS Nano 2013;7:2056-67. [25] Wan Z, Mao H, Guo M, Li Y, Zhu A, Yang H, et al. Highly efficient hierarchical micelles integrating photothermal therapy and singlet oxygen-synergized chemotherapy for cancer eradication. Theranostics 2014;4:399-411. [26] Yamaguchi F, Ogawa Y, Kikuchi M, Yuasa K, Motai H. Detection of gamma-Polyglutamic Acid (gamma-PGA) by SDS-Page. Biosci Biotechnol Biochem 1996;60:255-8. [27] Zia Q, Khan AA, Swaleha Z, Owais M. Self-assembled amphotericin B-loaded polyglutamic acid nanoparticles: preparation, characterization and in vitro potential against Candida albicans. Int J Nanomedicine 2015;10:1769-90. [28] Beziere N, Lozano N, Nunes A, Salichs J, Queiros D, Kostarelos K, Ntziachristos V. Dynamic imaging of PEGylated indocyanine green (ICG) liposomes within the tumor microenvironment using multi-spectral optoacoustic tomography (MSOT). Biomaterials 2015;37:415-24. [29] Rajian JR, Fabiilli ML, Fowlkes JB, Carson PL, Wang X. Drug delivery monitoring by photoacoustic tomography with an ICG encapsulated double emulsion. Opt Express 2011;19(15):14335-47. [30] Weigand R, Rotermund F, Penzkofer A. Aggregation dependent absorption reduction of indocyanine green. ‎J Phys Chem A 1997;101:7729-34. [31] Awasthi K, Nishimura G. Modification of near-infrared cyanine dyes by serum albumin protein. Photochem Photobiol Sci 2011;10:461-3. [32] Kirchherr AK, Briel A, Mader K. Stabilization of indocyanine green by encapsulation within micellar systems. Mol Pharm 2009;6:480-91. [33] Ng KK, Zheng G. Molecular interactions in organic nanoparticles for phototheranostic applications. Chem Rev 2015;115:11012-42. [34] Mordon S, Devoisselle JM, Soulie-Begu S, Desmettre T. Indocyanine green: physicochemical factors affecting its fluorescence in vivo. Microvasc Res 1998;55:146-52. [35] Kelkar SS, Hill TK, Marini FC, Mohs AM. Near infrared fluorescent nanoparticles based on hyaluronic acid: Self-assembly, optical properties, and cell interaction. Acta Biomater 2016;36:112-21. [36] Weng A, Manunta MD, Thakur M, Gilabert-Oriol R, Tagalakis AD, Eddaoudi A, Munye MM, Vink CA, Wiesner B, Eichhorst J, Melzig MF, Hart SL. Improved intracellular delivery of peptide- and lipid-nanoplexes by natural glycosides. J Control Release 2015;206:75-90. [37] Allen TM, Cullis PR. Drug delivery systems: entering the mainstream. Science 2004;303:1818-22. [38] Cabral H, Matsumoto Y, Mizuno K, Chen Q, Murakami M, Kimura M, et al. Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size. Nat Nanotechnol 2011;6:815-23. [39] Wong C, Stylianopoulos T, Cui J, Martin J, Chauhan VP, Jiang W, et al. Multistage nanoparticle delivery system for deep penetration into tumor tissue. Proc Natl Acad Sci U S A 2011;108:2426-31. [40] Choi HS, Liu W, Liu F, Nasr K, Misra P, Bawendi MG, et al. Design considerations for tumour-targeted nanoparticles. Nat Nanotechnol 2010;5:42-7. [41] Choi HS, Liu W, Misra P, Tanaka E, Zimmer JP, Itty Ipe B, et al. Renal clearance of quantum dots. Nat Biotechnol 2007;25:1165-70. [42] Mansour AM, Drevs J, Esser N, Hamada FM, Badary OA, Unger C, et al. A new approach for the treatment of malignant melanoma: enhanced antitumor efficacy of an albumin-binding doxorubicin prodrug that is cleaved by matrix metalloproteinase 2. Cancer Res 2003;63:4062-6. [43] Lee GY, Park K, Kim SY, Byun Y. MMPs-specific PEGylated peptide-DOX conjugate micelles that can contain free doxorubicin. Eur J Pharm Biopharm 2007;67:646-54. [44] Chen WH, Luo GF, Lei Q, Jia HZ, Hong S, Wang QR, et al. MMP-2 responsive polymeric micelles for cancer-targeted intracellular drug delivery. Chem Commun (Camb) 2015;51:465-8. [45] Jian WH, Yu TW, Chen CJ, Huang WC, Chiu HC, Chiang WH. Indocyanine green-encapsulated hybrid polymeric nanomicelles for photothermal cancer therapy. Langmuir 2015;31:6202-10. [46] Kawasaki G, Kato Y, Mizuno A. Cathepsin expression in oral squamous cell carcinoma: relationship with clinicopathologic factors. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;93:446-54. [47] Keereweer S, Mol IM, Kerrebijn JD, Van Driel PB, Xie B, Baatenburg de Jong RJ, et al. Targeting integrins and enhanced permeability and retention (EPR) effect for optical imaging of oral cancer. J Surg Oncol 2012;105:714-8. [48] Ochs, M.;Carregal-Romero, S.;Rejman, J.;Braeckmans, K.;De Smedt, S. C.; Parak, W. J. Light-addressable capsules as caged compound matrix for controlled triggering of cytosolic reactions. Angew. Chem. Int. Ed. Engl. 2013, 52, 695-699. [49] Zhu B, Li Y, Lin Z, Zhao M, Xu T, Wang C, Deng N. Silver nanoparticles induce HePG-2 cells apoptosis through ROS-mediated signaling pathways. Nanoscale Res Lett 2016;11(1):198. [50] Zhang Z, Wang J, Chen C. Near-Infrared light-mediated nanoplatforms for cancer thermo-chemotherapy and optical imaging. Adv Mater 2013;25(28):3869-80 [51] Berg K, Selbo PK, Prasmickaite L, Tjelle TE, Sandvig K, Moan J, et al. Photochemical internalization: a novel technology for delivery of macromolecules into cytosol. Cancer Res 1999;59:1180-3. [52] Philip R, Penzkofer A, Bäumler W, Szeimies RM, Abels C. Absorption and fluorescence spectroscopic investigation of indocyanine green. J Photochem Photobiol A Chem 1996;96:137-48.

PY - 2017/2/3

Y1 - 2017/2/3

N2 - Stimuli-responsive anticancer formulations can promote drug release and activation within the target tumour, facilitate cellular uptake, as well as improve the therapeutic efficacy of drugs and reduce off-target effects. In the present work, indocyanine green (ICG)-containing polyglutamate (PGA) nanoparticles were developed and characterized. Digestion of nanoparticles with cathepsin B, a matrix metalloproteinase overexpressed in the microenvironment of advanced tumours, decreased particle size and increased ICG cellular uptake. Incorporation of ICG in PGA nanoparticles provided the NIR-absorbing agent with time-dependent altered optical properties in the presence of cathepsin B. Having minimal dark toxicity, the formulation exhibited significant cytotoxicity upon NIR exposure. Combined use of the formulation with saporin, a ribosome-inactivating protein, resulted in synergistically enhanced cytotoxicity attributed to the photo-induced release of saporin from endo/lysosomes. The results suggest that this therapeutic approach can offer significant therapeutic benefit in the treatment of superficial malignancies, such as head and neck tumours.

AB - Stimuli-responsive anticancer formulations can promote drug release and activation within the target tumour, facilitate cellular uptake, as well as improve the therapeutic efficacy of drugs and reduce off-target effects. In the present work, indocyanine green (ICG)-containing polyglutamate (PGA) nanoparticles were developed and characterized. Digestion of nanoparticles with cathepsin B, a matrix metalloproteinase overexpressed in the microenvironment of advanced tumours, decreased particle size and increased ICG cellular uptake. Incorporation of ICG in PGA nanoparticles provided the NIR-absorbing agent with time-dependent altered optical properties in the presence of cathepsin B. Having minimal dark toxicity, the formulation exhibited significant cytotoxicity upon NIR exposure. Combined use of the formulation with saporin, a ribosome-inactivating protein, resulted in synergistically enhanced cytotoxicity attributed to the photo-induced release of saporin from endo/lysosomes. The results suggest that this therapeutic approach can offer significant therapeutic benefit in the treatment of superficial malignancies, such as head and neck tumours.

KW - indocyanine green

KW - polyglutamate

KW - cathepsin B

KW - near infra-red

KW - laser cancer treatment

U2 - 10.1088/1361-6528/28/5/055101

DO - 10.1088/1361-6528/28/5/055101

M3 - Article

VL - 28

JO - Nanotechnology

T2 - Nanotechnology

JF - Nanotechnology

SN - 0957-4484

IS - 5

ER -