Issue

Vol. 13 (2021)

Targeted Micellar Phthalocyanine for Lymph Node Metastasis Homing and Photothermal Therapy in an Orthotopic Colorectal Tumor Model

https://doi.org/10.1007/s40820-021-00666-8
Hai‑Yi Feng
Hongqiao International Institute of Medicine, Tongren Hospital and State Key Laboratory of Oncogenes and Related Genes, Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, People’s Republic of China
Yihang Yuan
Hongqiao International Institute of Medicine, Tongren Hospital and State Key Laboratory of Oncogenes and Related Genes, Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, People’s Republic of China
Yunpeng Zhang
Department of General Surgery, Tongren Hospital, SJTU-SM, Shanghai 200336, People’s Republic of China
Hai‑Jun Liu
Hongqiao International Institute of Medicine, Tongren Hospital and State Key Laboratory of Oncogenes and Related Genes, Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, People’s Republic of China
Xiao Dong
Hongqiao International Institute of Medicine, Tongren Hospital and State Key Laboratory of Oncogenes and Related Genes, Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, People’s Republic of China
Si‑Cong Yang
Hongqiao International Institute of Medicine, Tongren Hospital and State Key Laboratory of Oncogenes and Related Genes, Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, People’s Republic of China
Xue‑Liang Liu
Hongqiao International Institute of Medicine, Tongren Hospital and State Key Laboratory of Oncogenes and Related Genes, Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, People’s Republic of China
Xing Lai
Hongqiao International Institute of Medicine, Tongren Hospital and State Key Laboratory of Oncogenes and Related Genes, Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, People’s Republic of China
Mao‑Hua Zhu
Hongqiao International Institute of Medicine, Tongren Hospital and State Key Laboratory of Oncogenes and Related Genes, Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, People’s Republic of China
Jue Wang
Department of General Surgery, Tongren Hospital, SJTU-SM, Shanghai 200336, People’s Republic of China
Qin Lu
Hongqiao International Institute of Medicine, Tongren Hospital and State Key Laboratory of Oncogenes and Related Genes, Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, People’s Republic of China
Quanjun Lin
Department of General Surgery, Tongren Hospital, SJTU-SM, Shanghai 200336, People’s Republic of China
Hong‑Zhuan Chen
Institute of Interdisciplinary Integrative Biomedical Research, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, People’s Republic of China
Jonathan F. Lovell
Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY 14260, USA
Peng Sun
Department of General Surgery, Tongren Hospital, SJTU-SM, Shanghai 200336, People’s Republic of China
Chao Fang
Hongqiao International Institute of Medicine, Tongren Hospital and State Key Laboratory of Oncogenes and Related Genes, Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, People’s Republic of China

Corresponding Author: Chao Fang

fangchao32@sjtu.edu.cn

Nano-Micro Letters, Vol. 13 (2021), Article Number: 145

Abstract

Tumor lymph node (LN) metastasis seriously affects the treatment prognosis. Studies have shown that nanoparticles with size of sub-50 nm can directly penetrate into LN metastases after intravenous administration. Here, we speculate through introducing targeting capacity, the nanoparticle accumulation in LN metastases would be further enhanced for improved local treatment such as photothermal therapy. Trastuzumab-targeted micelles (< 50 nm) were formulated using a unique surfactant-stripping approach that yielded concentrated phthalocyanines with strong near-infrared absorption. Targeted micellar phthalocyanine (T-MP) was an effective photothermal transducer and ablated HT-29 cells in vitro. A HER2-expressing colorectal cancer cell line (HT-29) was used to establish an orthotopic mouse model that developed metastatic disease in mesenteric sentinel LN. T-MP accumulated more in the LN metastases compared to the micelles conjugated with control IgG. Following surgical resection of the primary tumor, minimally invasive photothermal treatment of the metastatic LN with T-MP, but not the control micelles, extended mouse survival. Our findings demonstrate for the first time that targeted small-sized nanoparticles have potential to enable superior paradigms for dealing with LN metastases.


Highlights:


1 Small-sized trastuzumab-targeted micelles (T-MP) were engineered using a surfactant-stripping approach that yielded concentrated phthalocyanines with strong near infrared absorption.
2 T-MP accumulated more in the lymph node (LN) metastases of orthotopic colorectal cancer compared to the micelles conjugated with control IgG.
3 Following surgical resection of the primary tumor, minimally invasive photothermal treatment of the metastatic LN with T-MP, but not the control micelles, extended mouse survival.

Keywords

Lymph node metastasis Photothermal therapy Trastuzumab Phthalocyanine Micelles
Feng, Hai‑Yi, Yihang Yuan, Yunpeng Zhang, Hai‑Jun Liu, Xiao Dong, Si‑Cong Yang, Xue‑Liang Liu, Xing Lai, Mao‑Hua Zhu, Jue Wang, Qin Lu, Quanjun Lin, Hong‑Zhuan Chen, Jonathan F. Lovell, Peng Sun, and Chao Fang. 2021. “Targeted Micellar Phthalocyanine for Lymph Node Metastasis Homing and Photothermal Therapy in an Orthotopic Colorectal Tumor Model”. Nano-Micro Letters 13 (June):145. https://doi.org/10.1007/s40820-021-00666-8.
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX
References
  1. S.A. Stacker, S.P. Williams, T. Karnezis, R. Shayan, S.B. Fox et al., Lymphangiogenesis and lymphatic vessel remodelling in cancer. Nat. Rev. Cancer 14, 159–172 (2014). https://doi.org/10.1038/nrc3677
  2. E.R. Pereira, D. Kedrin, G. Seano, O. Gautier, E.F.J. Meijer et al., Lymph node metastases can invade local blood vessels, exit the node, and colonize distant organs in mice. Science 359, 1403–1407 (2018). https://doi.org/10.1126/science.aal3622
  3. P. Harter, J. Sehouli, D. Lorusso, A. Reuss, I. Vergote et al., A randomized trial of lymphadenectomy in patients with advanced ovarian neoplasms. N. Engl. J. Med. 380, 822–832 (2019). https://doi.org/10.1056/NEJMoa1808424
  4. E. Van Cutsem, X. Sagaert, B. Topal, K. Haustermans, H. Prenen, Gastric cancer. Lancet 388, 2654–2664 (2016). https://doi.org/10.1016/S0140-6736(16)30354-3
  5. I.G. Kwon, T. Son, H.I. Kim, W.J. Hyung, Fluorescent lymphography-guided lymphadenectomy during robotic radical gastrectomy for gastric cancer. JAMA Surg. 154, 150–158 (2019). https://doi.org/10.1001/jamasurg.2018.4267
  6. J. Liu, H.J. Li, Y.L. Luo, C.F. Xu, X.J. Du et al., Enhanced primary tumor penetration facilitates nanoparticle draining into lymph nodes after systemic injection for tumor metastasis inhibition. ACS Nano 13, 8648–8658 (2019). https://doi.org/10.1021/acsnano.9b03472
  7. H. Cabral, J. Makino, Y. Matsumoto, P. Mi, H. Wu et al., Systemic targeting of lymph node metastasis through the blood vascular system by using size-controlled nanocarriers. ACS Nano 9, 4957–4967 (2015). https://doi.org/10.1021/nn5070259
  8. X.Y. Zhang, W.Y. Lu, Recent advances in lymphatic targeted drug delivery system for tumor metastasis. Cancer Biol. Med. 11, 247–254 (2014).
  9. Z. Yan, F. Wang, Z. Wen, C. Zhan, L. Feng et al., LyP-1-conjugated PEGylated liposomes: a carrier system for targeted therapy of lymphatic metastatic tumor. J. Control. Release 157, 118–125 (2012). https://doi.org/10.1016/j.jconrel.2011.07.034
  10. X. Li, Q. Dong, Z. Yan, W. Lu, L. Feng et al., MPEG-DSPE polymeric micelle for translymphatic chemotherapy of lymph node metastasis. Int. J. Pharm. 487, 8–16 (2015). https://doi.org/10.1016/j.ijpharm.2015.03.074
  11. W. Yu, R. Liu, Y. Zhou, H. Gao, Size-tunable strategies for a tumor targeted drug delivery system. ACS Cent. Sci. 6, 100–116 (2020). https://doi.org/10.1021/acscentsci.9b01139
  12. W. Zhang, F. Wang, C. Hu, Y. Zhou, H. Gao et al., The progress and perspective of nanoparticle-enabled tumor metastasis treatment. Acta Pharm. Sin. B 10, 2037–2053 (2020). https://doi.org/10.1016/j.apsb.2020.07.013
  13. S.K. Golombek, J.N. May, B. Theek, L. Appold, N. Drude et al., Tumor targeting via EPR: Strategies to enhance patient responses. Adv. Drug Deliv. Rev. 130, 17–38 (2018). https://doi.org/10.1016/j.addr.2018.07.007
  14. J. Ding, J. Chen, L. Gao, Z. Jiang, Y. Zhang et al., Engineered nanomedicines with enhanced tumor penetration. Nano Today 29, 100800 (2019). https://doi.org/10.1016/j.nantod.2019.100800
  15. J. Chen, J. Ding, Y. Wang, J. Cheng, S. Ji et al., Sequentially responsive shell-stacked nanoparticles for deep penetration into solid tumors. Adv. Mater. 29, 1701170 (2017). https://doi.org/10.1002/adma.201701170
  16. P. Mi, H. Cabral, K. Kataoka, Ligand-installed nanocarriers toward precision therapy. Adv. Mater. 32, 1902604 (2020). https://doi.org/10.1002/adma.201902604
  17. S. He, Y. Jiang, J. Li, K. Pu, Semiconducting polycomplex nanoparticles for photothermal ferrotherapy of cancer. Angew. Chem. Int. Ed. 59, 10633–10638 (2020). https://doi.org/10.1002/anie.202003004
  18. J. Li, D. Cui, Y. Jiang, J. Huang, P. Cheng et al., Near-infrared photoactivatable semiconducting polymer nanoblockaders for metastasis-inhibited combination cancer therapy. Adv. Mater. 31, 1905091 (2019). https://doi.org/10.1002/adma.201905091
  19. Y. Zhang, M. Jeon, L.J. Rich, H. Hong, J. Geng et al., Non-invasive multimodal functional imaging of the intestine with frozen micellar naphthalocyanines. Nat. Nanotechnol. 9, 631–638 (2014). https://doi.org/10.1038/nnano.2014.130
  20. Y. Zhang, D. Wang, S. Goel, B. Sun, U. Chitgupi et al., Surfactant-stripped frozen pheophytin micelles for multimodal gut imaging. Adv. Mater. 28, 8524–8530 (2016). https://doi.org/10.1002/adma.201602373
  21. U. Chitgupi, N. Nyayapathi, J. Kim, D. Wang, B. Sun et al., Surfactant-stripped micelles for NIR-II photoacoustic imaging through 12 cm of breast tissue and whole human breasts. Adv. Mater. 31, 1902279 (2019). https://doi.org/10.1002/adma.201902279
  22. A. Beji, D. Horst, J. Engel, T. Kirchner, A. Ullrich, Toward the prognostic significance and therapeutic potential of HER3 receptor tyrosine kinase in human colon cancer. Clin. Cancer Res. 18, 956–968 (2012). https://doi.org/10.1158/1078-0432.CCR-11-1186
  23. H. Xu, Y. Yu, D. Marciniak, A.K. Rishi, F.H. Sarkar et al., Epidermal growth factor receptor (EGFR)-related protein inhibits multiple members of the EGFR family in colon and breast cancer cells. Mol. Cancer Ther. 4, 435–442 (2005). https://doi.org/10.1158/1535-7163.MCT-04-0280
  24. H.-J. Liu, X. Luan, H.-Y. Feng, X. Dong, S.-C. Yang et al., Integrated combination treatment using a “smart” chemotherapy and microrna delivery system improves outcomes in an orthotopic colorectal cancer model. Adv. Funct. Mater. 28, 1801118 (2018). https://doi.org/10.1002/adfm.201801118
  25. W. Zhang, K. Gilstrap, L. Wu, C.R. K, M.A. Moss et al., Synthesis and characterization of thermally responsive Pluronic F127-chitosan nanocapsules for controlled release and intracellular delivery of small molecules. ACS Nano 4, 6747–6759 (2010). https://doi.org/10.1021/nn101617n
  26. H. Yang, Q.V. Le, G. Shim, Y.K. Oh, Y.K. Shin, Molecular engineering of antibodies for site-specific conjugation to lipid polydopamine hybrid nanoparticles. Acta Pharm. Sin. B 10, 2212–2226 (2020). https://doi.org/10.1016/j.apsb.2020.07.006
  27. Y. Jiang, X. Zhao, J. Huang, J. Li, P.K. Upputuri et al., Transformable hybrid semiconducting polymer nanozyme for second near-infrared photothermal ferrotherapy. Nat. Commun. 11, 1857 (2020). https://doi.org/10.1038/s41467-020-15730-x
  28. M. Cui, S. Liu, B. Song, D. Guo, J. Wang et al., Fluorescent silicon nanorods-based nanotheranostic agents for multimodal imaging-guided photothermal therapy. Nano-Micro Lett. 11, 73 (2019). https://doi.org/10.1007/s40820-019-0306-9
  29. D. Wang, H. Wu, J. Zhou, P. Xu, C. Wang et al., In situ one-pot synthesis of MOF-polydopamine hybrid nanogels with enhanced photothermal effect for targeted cancer therapy. Adv. Sci. 5, 1800287 (2018). https://doi.org/10.1002/advs.201800287
  30. Z.-J. Chen, S.-C. Yang, X.-L. Liu, Y. Gao, X. Dong et al., Nanobowl-supported liposomes improve drug loading and delivery. Nano Lett. 20, 4177–4187 (2020). https://doi.org/10.1021/acs.nanolett.0c00495
  31. W. Shan, R. Chen, Q. Zhang, J. Zhao, B. Chen et al., Improved stable indocyanine green (ICG)-mediated cancer optotheranostics with naturalized hepatitis B core particles. Adv. Mater. 30, 1707567 (2018). https://doi.org/10.1002/adma.201707567
  32. H.J. Li, J.Z. Du, X.J. Du, C.F. Xu, C.Y. Sun et al., Stimuli-responsive clustered nanoparticles for improved tumor penetration and therapeutic efficacy. Proc. Natl. Acad. Sci. U.S.A. 113, 4164–4169 (2016). https://doi.org/10.1073/pnas.1522080113
  33. A. Pittobarry, N.P.E. Barry, Pluronic® block-copolymers in medicine: from chemical and biological versatility to rationalisation and clinical advances. Polym. Chem. 5, 3291–3297 (2014). https://doi.org/10.1039/C4PY00039K
  34. D.H. Yu, Q. Lu, J. Xie, C. Fang, H.Z. Chen, Peptide-conjugated biodegradable nanoparticles as a carrier to target paclitaxel to tumor neovasculature. Biomaterials 31, 2278–2292 (2010). https://doi.org/10.1016/j.biomaterials.2009.11.047
  35. H. Wang, G.R. Williams, J. Wu, J. Wu, S. Niu et al., Pluronic F127-based micelles for tumor-targeted bufalin delivery. Int. J. Pharm. 559, 289–298 (2019). https://doi.org/10.1016/j.ijpharm.2019.01.049
  36. Y. Zhang, W. Song, J. Geng, U. Chitgupi, H. Unsal et al., Therapeutic surfactant-stripped frozen micelles. Nat. Commun. 7, 11649 (2016). https://doi.org/10.1038/ncomms11649
  37. Y. Zhang, L. Feng, J. Wang, D. Tao, C. Liang et al., Surfactant-stripped micelles of near infrared dye and paclitaxel for photoacoustic imaging guided photothermal-chemotherapy. Small 14, 1802991 (2018). https://doi.org/10.1002/smll.201802991
  38. J. Li, K. Pu, Semiconducting polymer nanomaterials as near-infrared photoactivatable protherapeutics for cancer. Acc. Chem. Res. 53, 752–762 (2020). https://doi.org/10.1021/acs.accounts.9b00569
  39. C. Xu, K. Pu, Second near-infrared photothermal materials for combinational nanotheranostics. Chem. Soc. Rev. 50, 1111–1137 (2021). https://doi.org/10.1039/D0CS00664E
  40. D.Y. Oh, Y.J. Bang, HER2-targeted therapies - a role beyond breast cancer. Nat. Rev. Clin. Oncol. 17, 33–48 (2020). https://doi.org/10.1038/s41571-019-0268-3
  41. F. Meric-Bernstam, H. Hurwitz, K.P.S. Raghav, R.R. McWilliams, M. Fakih et al., Pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer (MyPathway): an updated report from a multicentre, open-label, phase 2a, multiple basket study. Lancet Oncol. 20, 518–530 (2019). https://doi.org/10.1016/S1470-2045(18)30904-5
  42. A. Sartore-Bianchi, S. Marsoni, S. Siena, Human epidermal growth factor receptor 2 as a molecular biomarker for metastatic colorectal cancer. JAMA Oncol. 4, 19–20 (2018). https://doi.org/10.1001/jamaoncol.2017.3323
  43. S. Togami, R. Kubo, T. Kawamura, S. Yanazume, M. Kamio, H. Kobayashi, Risk factors for lymphatic complications following lymphadenectomy in patients with endometrial cancer. Taiwan. J. Obstet. Gynecol. 59, 420–424 (2020). https://doi.org/10.1016/j.tjog.2020.03.015
  44. D. Luo, S. Goel, H.J. Liu, K.A. Carter, D. Jiang et al., Intrabilayer 64Cu labeling of photoactivatable, doxorubicin-loaded stealth liposomes. ACS Nano 11, 12482–12491 (2017). https://doi.org/10.1021/acsnano.7b06578
Read More
Author biographies are not available.
Download this PDF file
PDF SUPPLEMENTARY MATERIAL
Statistic
Read Counter : 5502 Download : 4127

Most read articles by the same author(s)