Evaluation of the Targeting and Therapeutic Efficiency of Anti-EGFR Functionalised Nanoparticles in Head and Neck Cancer Cells for Use in NIR-II Optical Window
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Culture
2.2. Flow Cytometry
2.3. Immunofluorescence Imaging (IF)
2.4. Gold Nanorods (AuNRs)
2.5. Cytotoxicity Assay
2.6. Quantification of AuNR Targeting
2.7. Photothermal Therapy
2.8. Apoptosis and Necrosis
3. Results
3.1. EGFR Is Highly Expressed in HNSCC Cell Lines
3.2. AuNRs Cytotoxicity
3.3. In Vitro Targeting Efficiency
3.4. NIR-II Photothermal Therapy (PTT) Significantly Increased Cancer Cell Death in Head and Neck Cancer
3.5. Combination of tAuNRs and Laser Therapy Caused Cell Death by Apoptosis
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Licitra, L.E.; Felip, E. Squamous cell carcinoma of the head and neck: ESMO Clinical Recommendations for diagnosis, treatment and follow-up. Ann. Oncol. 2009, 20 (Suppl. 4), iv121–iv122. [Google Scholar] [CrossRef]
- Li, H.; Wawrose, J.S.; Gooding, W.E.; Garraway, L.A.; Lui, V.W.Y.; Peyser, N.D.; Grandis, J.R. Genomic analysis of head and neck squamous cell carcinoma cell lines and human tumors: A rational approach to preclinical model selection. Mol. Cancer Res. 2014, 12, 571–582. [Google Scholar] [CrossRef] [Green Version]
- Grégoire, V.; Lefebvre, J.-L.; Licitra, L.; Felip, E. The EHNS–ESMO–ESTRO Guidelines Working Group. Squamous cell carcinoma of the head and neck: EHNS–ESMO–ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2010, 21 (Suppl. 5), v184–v186. [Google Scholar] [CrossRef] [PubMed]
- Wise-Draper, T.M.; Draper, D.J.; Gutkind, J.S.; Molinolo, A.A.; Wikenheiser-Brokamp, K.A.; Wells, S.I. Future directions and treatment strategies for head and neck squamous cell carcinomas. Transl. Res. 2012, 160, 167–177. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bourhis, J.; Lapeyre, M.; Tortochaux, J.; Rives, M.; Aghili, M.; Bourdin, S.; Lesaunier, F.; Benassi, T.; Lemanski, C.; Geoffrois, L.; et al. Phase III Randomized Trial of Very Accelerated Radiation Therapy Compared With Conventional Radiation Therapy in Squamous Cell Head and Neck Cancer: A GORTEC Trial. J. Clin. Oncol. 2006, 24, 2873–2878. [Google Scholar] [CrossRef] [PubMed]
- Gupta, T.; Kannan, S.; Ghosh-Laskar, S.; Agarwal, J.P. Systematic review and meta-analyses of intensity-modulated radiation therapy versus conventional two-dimensional and/or or three-dimensional radiotherapy in curative-intent management of head and neck squamous cell carcinoma. PLoS ONE 2018, 13, e0200137. [Google Scholar] [CrossRef] [PubMed]
- Savard, J.; Ivers, H.; Savard, M.-H.; Morin, C.M. Cancer treatments and their side effects are associated with aggravation of insomnia: Results of a longitudinal study. Cancer 2015, 121, 1703–1711. [Google Scholar] [CrossRef] [PubMed]
- Chung, C.H.; Parker, J.S.; Karaca, G.; Wu, J.; Funkhouser, W.K.; Moore, D.; Butterfoss, D.; Xiang, D.; Zanation, A.; Yin, X.; et al. Molecular classification of head and neck squamous cell carcinomas using patterns of gene expression. Cancer Cell 2004, 5, 489–500. [Google Scholar] [CrossRef] [Green Version]
- Walter, V.; Yin, X.; Wilkerson, M.D.; Cabanski, C.R.; Zhao, N.; Du, Y.; Ang, M.K.; Hayward, M.C.; Salazar, A.H.; Hoadley, K.A.; et al. Molecular subtypes in head and neck cancer exhibit distinct patterns of chromosomal gain and loss of canonical cancer genes. PLoS ONE 2013, 8, e56823. [Google Scholar] [CrossRef]
- Jiang, Y.; Sun, M.; Ouyang, N.; Tang, Y.; Miao, P. Synergistic Chemo-thermal Therapy of Cancer by DNA-Templated Silver Nanoclusters and Polydopamine Nanoparticles. ACS Appl. Mater. Interfaces 2021, 13, 21653–21660. [Google Scholar] [CrossRef] [PubMed]
- Taberna, M.; Oliva, M.; Mesía, R. Cetuximab-Containing Combinations in Locally Advanced and Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. Front. Oncol. 2019, 9, 383. [Google Scholar] [CrossRef]
- Baker, S.; Ali, I.; Silins, I.; Pyysalo, S.; Guo, Y.; Högberg, J.; Stenius, U.; Korhonen, A. Cancer Hallmarks Analytics Tool (CHAT): A text mining approach to organize and evaluate scientific literature on cancer. Bioinformatics 2017, 33, 3973–3981. [Google Scholar] [CrossRef]
- Ward, T.H.; Cummings, J.; Dean, E.; Greystoke, A.; Hou, J.M.; Backen, A.; Ranson, M.; Dive, C. Biomarkers of apoptosis. Br. J. Cancer 2008, 99, 841–846. [Google Scholar] [CrossRef] [Green Version]
- Xu, X.; Lu, H.; Lee, R. Near Infrared Light Triggered Photo/Immuno-Therapy Toward Cancers. Front. Bioeng. Biotechnol. 2020, 8, 488. [Google Scholar] [CrossRef]
- Tabish, T.A.; Dey, P.; Mosca, S.; Salimi, M.; Palombo, F.; Matousek, P.; Stone, N. Smart Gold Nanostructures for Light Mediated Cancer Theranostics: Combining Optical Diagnostics with Photothermal Therapy. Adv. Sci. 2020, 7, 1903441. [Google Scholar] [CrossRef] [PubMed]
- Deng, X.; Shao, Z.; Zhao, Y. Solutions to the Drawbacks of Photothermal and Photodynamic Cancer Therapy. Adv. Sci. 2021, 8, 2002504. [Google Scholar] [CrossRef]
- Aoki, H.; Nojiri, M.; Mukai, R.; Ito, S. Near-infrared absorbing polymer nano-particle as a sensitive contrast agent for photo-acoustic imaging. Nanoscale 2015, 7, 337–343. [Google Scholar] [CrossRef] [PubMed]
- Phan, T.T.V.; Bui, N.Q.; Cho, S.-W.; Bharathiraja, S.; Manivasagan, P.; Moorthy, M.S.; Mondal, S.; Kim, C.-S.; Oh, J. Photoacoustic Imaging-Guided Photothermal Therapy with Tumor-Targeting HA-FeOOH@PPy Nanorods. Sci. Rep. 2018, 8, 8809. [Google Scholar] [CrossRef] [Green Version]
- Zou, L.; Wang, H.; He, B.; Zeng, L.; Tan, T.; Cao, H.; He, X.; Zhang, Z.; Guo, S.; Li, Y. Current Approaches of Photothermal Therapy in Treating Cancer Metastasis with Nanotherapeutics. Theranostics 2016, 6, 762–772. [Google Scholar] [CrossRef] [PubMed]
- Debbage, P.; Jaschke, W. Molecular imaging with nanoparticles: Giant roles for dwarf actors. Histochem. Cell Biol. 2008, 130, 845–875. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhu, S.; Yung, B.C.; Chandra, S.; Niu, G.; Antaris, A.L.; Chen, X. Near-Infrared-II (NIR-II) Bioimaging via Off-Peak NIR-I Fluorescence Emission. Theranostics 2018, 8, 4141–4151. [Google Scholar] [CrossRef] [PubMed]
- Tao, Z.; Dang, X.; Huang, X.; Muzumdar, M.; Xu, E.S.; Bardhan, N.M.; Song, H.; Qi, R.; Yu, Y.; Li, T.; et al. Early tumor detection afforded by in vivo imaging of near-infrared II fluorescence. Biomaterials 2017, 134, 202–215. [Google Scholar] [CrossRef] [PubMed]
- Zhao, J.; Zhong, D.; Zhou, S. NIR-I-to-NIR-II fluorescent nanomaterials for biomedical imaging and cancer therapy. J. Mater. Chem. B 2018, 6, 349–365. [Google Scholar] [CrossRef] [PubMed]
- Ge, X.; Fu, Q.; Bai, L.; Chen, B.; Wang, R.; Gao, S.; Song, J. Photoacoustic imaging and photothermal therapy in the second near-infrared window. New J. Chem. 2019, 43, 8835–8851. [Google Scholar] [CrossRef] [Green Version]
- Ge, X.; Fu, Q.; Su, L.; Li, Z.; Zhang, W.; Chen, T.; Yang, H.; Song, J. Light-activated gold nanorod vesicles with NIR-II fluorescence and photoacoustic imaging performances for cancer theranostics. Theranostics 2020, 10, 4809–4821. [Google Scholar] [CrossRef] [PubMed]
- Roach, L.; Ye, S.; Moorcroft, S.C.T.; Critchley, K.; Coletta, P.L.; Evans, S.D. Morphological control of seedlessly-synthesized gold nanorods using binary surfactants. Nanotechnology 2018, 29, 135601. [Google Scholar] [CrossRef]
- Chen, Y.-S.; Zhao, Y.; Yoon, S.J.; Gambhir, S.S.; Emelianov, S. Miniature gold nanorods for photoacoustic molecular imaging in the second near-infrared optical window. Nat. Nanotechnol. 2019, 14, 465–472. [Google Scholar] [CrossRef]
- Smith, M.A.; Mancini, M.C.; Nie, S. Bioimaging: Second window for in vivo imaging. Nat. Nanotechnol. 2009, 4, 710. [Google Scholar] [CrossRef] [Green Version]
- Amendola, V.; Pilot, R.; Frasconi, M.; Marago, O.M.; Iatì, M.A. Surface plasmon resonance in gold nanoparticles: A review. J. Phys. Condens. Matter 2017, 29, 203002. [Google Scholar] [CrossRef]
- Guo, J.; Rahme, K.; He, Y.; Li, L.-L.; Holmes, J.D.; O’Driscoll, C.M. Gold nanoparticles enlighten the future of cancer theranostics. Int. J. Nanomed. 2017, 12, 6131–6152. [Google Scholar] [CrossRef] [Green Version]
- Lewinski, N.; Colvin, V.; Drezek, R. Cytotoxicity of Nanoparticles. Small 2008, 4, 26–49. [Google Scholar] [CrossRef]
- Jain, P.; Lee, K.S.; El-Sayed, I.H.; El-Sayed, M.A. Calculated Absorption and Scattering Properties of Gold Nanoparticles of Different Size, Shape, and Composition: Applications in Biological Imaging and Biomedicine. J. Phys. Chem. B 2006, 110, 7238–7248. [Google Scholar] [CrossRef] [Green Version]
- Cao, J.; Zhu, B.; Zheng, K.; He, S.; Meng, L.; Song, J.; Yang, H. Recent Progress in NIR-II Contrast Agent for Biological Imaging. Front. Bioeng. Biotechnol. 2019, 7, 487. [Google Scholar] [CrossRef] [Green Version]
- Alexis, F.; Pridgen, E.; Molnar, L.K.; Farokhzad, O.C. Factors Affecting the Clearance and Biodistribution of Polymeric Nanoparticles. Mol. Pharm. 2008, 5, 505–515. [Google Scholar] [CrossRef] [Green Version]
- Gabizon, A.; Catane, R.; Uziely, B.; Kaufman, B.; Safra, T.; Cohen, R.; Martin, F.; Huang, A.; Barenholz, Y. Prolonged circulation time and enhanced accumulation in malignant exudates of doxorubicin encapsulated in poly-ethylene-glycol coated liposomes. Cancer Res. 1994, 54, 987–992. [Google Scholar]
- Yetisgin, A.A.; Cetinel, S.; Zuvin, M.; Kosar, A.; Kutlu, O. Therapeutic Nanoparticles and Their Targeted Delivery Applications. Molecules 2020, 25, 2193. [Google Scholar] [CrossRef]
- Juan, A.; Cimas, F.J.; Bravo, I.; Pandiella, A.; Ocaña, A.; Alonso-Moreno, C. An Overview of Antibody Conjugated Polymeric Nanoparticles for Breast Cancer Therapy. Pharmaceutics 2020, 12, 802. [Google Scholar] [CrossRef]
- Joshi, P.P.; Yoon, S.J.; Hardin, W.; Emelianov, S.; Sokolov, K.V. Conjugation of Antibodies to Gold Nanorods through Fc Portion: Synthesis and Molecular Specific Imaging. Bioconjugate Chem. 2013, 24, 878–888. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Huang, X.; Neretina, S.; El-Sayed, M.A. Gold Nanorods: From Synthesis and Properties to Biological and Biomedical Applications. Adv. Mater. 2009, 21, 4880–4910. [Google Scholar] [CrossRef] [PubMed]
- Wan, J.; Wang, J.; Liu, T.; Xie, Z.; Yu, X.-F.; Li, W. Surface chemistry but not aspect ratio mediates the biological toxicity of gold nanorods in vitro and in vivo. Sci. Rep. 2015, 5, 11398. [Google Scholar] [CrossRef] [PubMed]
- Lau, I.P.; Chen, H.; Wang, J.; Ong, H.C.; Leung, K.C.-F.; Ho, H.P.; Kong, S.K. In vitro effect of CTAB-and PEG-coated gold nanorods on the induction of eryptosis/erythroptosis in human erythrocytes. Nanotoxicology 2012, 6, 847–856. [Google Scholar] [CrossRef]
- Niidome, T.; Yamagata, M.; Okamoto, Y.; Akiyama, Y.; Takahashi, H.; Kawano, T.; Katayama, Y.; Niidome, Y. PEG-modified gold nanorods with a stealth character for in vivo applications. J. Control. Release 2006, 114, 343–347. [Google Scholar] [CrossRef]
- Jain, A.; Barve, A.; Zhao, Z.; Jin, W.; Cheng, K. Comparison of Avidin, Neutravidin, and Streptavidin as Nanocarriers for Efficient siRNA Delivery. Mol. Pharm. 2017, 14, 1517–1527. [Google Scholar] [CrossRef]
- Upputuri, P.K.; Pramanik, M. Photoacoustic imaging in the second near-infrared window: A review. J. Biomed. Opt. 2019, 24, 040901. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mayerhöfer, T.G. Employing Theories Far beyond Their Limits - Linear Dichroism Theory. ChemPhysChem 2018, 19, 2123–2130. [Google Scholar] [CrossRef] [PubMed]
- Scarabelli, L.; Sánchez-Iglesias, A.; Pérez-Juste, J.; Liz-Marzán, L.M. A “Tips and Tricks” Practical Guide to the Synthesis of Gold Nanorods. J. Phys. Chem. Lett. 2015, 6, 4270–4279. [Google Scholar] [CrossRef] [Green Version]
- Busch, R.T.; Karim, F.; Weis, J.; Sun, Y.; Zhao, C.; Vasquez, E.S. Optimization and Structural Stability of Gold Nanoparticle–Antibody Bioconjugates. ACS Omega 2019, 4, 15269–15279. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Montenegro, J.-M.; Grazu, V.; Sukhanova, A.; Agarwal, S.; de la Fuente, J.M.; Nabiev, I.; Greiner, A.; Parak, W.J. Controlled antibody/(bio-) conjugation of inorganic nanoparticles for targeted delivery. Adv. Drug Deliv. Rev. 2013, 65, 677–688. [Google Scholar] [CrossRef] [PubMed]
- Knights, O.; Freear, S.; McLaughlan, J.R. Improving Plasmonic Photothermal Therapy of Lung Cancer Cells with Anti-EGFR Targeted Gold Nanorods. Nanomaterials 2020, 10, 1307. [Google Scholar] [CrossRef]
- Taylor, R.; Cullen, S.P.; Martin, S. Apoptosis: Controlled demolition at the cellular level. Nat. Rev. Mol. Cell Biol. 2008, 9, 231–241. [Google Scholar] [CrossRef]
- Liszbinski, R.B.; Romagnoli, G.G.; Gorgulho, C.M.; Basso, C.R.; Pedrosa, V.A.; Kaneno, R. Anti-EGFR-Coated Gold Nanoparticles In Vitro Carry 5-Fluorouracil to Colorectal Cancer Cells. Materials 2020, 13, 375. [Google Scholar] [CrossRef] [Green Version]
- Liu, J.; Liang, Y.; Liu, T.; Li, D.; Yang, X. Anti-EGFR-Conjugated Hollow Gold Nanospheres Enhance Radiocytotoxic Targeting of Cervical Cancer at Megavoltage Radiation Energies. Nanoscale Res. Lett. 2015, 10, 218. [Google Scholar] [CrossRef] [Green Version]
- Li, S.; Bouchy, S.; Penninckx, S.; Marega, R.; Fichera, O.; Gallez, B.; Feron, O.; Martinive, P.; Heuskin, A.-C.; Michiels, C.; et al. Antibody-functionalized gold nanoparticles as tumor-targeting radiosensitizers for proton therapy. Nanomedicine 2019, 14, 317–333. [Google Scholar] [CrossRef]
- Khaznadar, S.S.; Khan, M.; Schmid, E.; Gebhart, S.; Becker, E.-T.; Krahn, T.; Von Ahsen, O. EGFR overexpression is not common in patients with head and neck cancer. Cell lines are not representative for the clinical situation in this indication. Oncotarget 2018, 9, 28965–28975. [Google Scholar] [CrossRef]
- Phuc, L.T.M.; Taniguchi, A. Epidermal Growth Factor Enhances Cellular Uptake of Polystyrene Nanoparticles by Clathrin-Mediated Endocytosis. Int. J. Mol. Sci. 2017, 18, 1301. [Google Scholar] [CrossRef] [Green Version]
- Zhao, Y.; Liu, W.; Tian, Y.; Yang, Z.; Wang, X.; Zhang, Y.; Tang, Y.; Zhao, S.; Wang, C.; Liu, Y.; et al. Anti-EGFR Peptide-Conjugated Triangular Gold Nanoplates for Computed Tomography/Photoacoustic Imaging-Guided Photothermal Therapy of Non-Small Cell Lung Cancer. ACS Appl. Mater. Interfaces 2018, 10, 16992–17003. [Google Scholar] [CrossRef] [PubMed]
- Yang, H.; He, H.; Tong, Z.; Xia, H.; Mao, Z.; Gao, C. The impact of size and surface ligand of gold nanorods on liver cancer accumulation and photothermal therapy in the second near-infrared window. J. Colloid Interface Sci. 2020, 565, 186–196. [Google Scholar] [CrossRef]
- Manivasagan, P.; Bharathiraja, S.; Moorthy, M.S.; Oh, Y.-O.; Song, K.; Seo, H.; Oh, J. Anti-EGFR Antibody Conjugation of Fucoidan-Coated Gold Nanorods as Novel Photothermal Ablation Agents for Cancer Therapy. ACS Appl. Mater. Interfaces 2017, 9, 14633–14646. [Google Scholar] [CrossRef] [PubMed]
- Awasthi, R.; Roseblade, A.; Hansbro, P.; Rathbone, M.J.; Dua, K.; Bebawy, M. Nanoparticles in Cancer Treatment: Opportunities and Obstacles. Curr. Drug Targets 2018, 19, 1696–1709. [Google Scholar] [CrossRef] [PubMed]
- Ávalos, A.; Haza, A.I.; Mateo, D.; Morales, P. In vitro and in vivo genotoxicity assessment of gold nanoparticles of different sizes by comet and SMART assays. Food Chem. Toxicol. 2018, 120, 81–88. [Google Scholar] [CrossRef] [PubMed]
- Dykman, L.A.; Khlebtsov, N.G. Gold nanoparticles in biology and medicine: Recent advances and prospects. Acta Nat. 2011, 3, 34–55. [Google Scholar] [CrossRef] [Green Version]
- Zhang, M.; Kim, H.S.; Jin, T.; Woo, J.; Piao, Y.J.; Moon, W.K. Near-infrared photothermal therapy using anti-EGFR-gold nanorod conjugates for triple negative breast cancer. Oncotarget 2017, 8, 86566. [Google Scholar] [CrossRef] [Green Version]
- Kao, H.-W.; Lin, Y.-Y.; Chen, C.-C.; Chi, K.-H.; Tien, D.-C.; Hsia, C.-C.; Lin, M.-H.; Wang, H.-E. Evaluation of EGFR-targeted radioimmuno-gold-nanoparticles as a theranostic agent in a tumor animal model. Bioorganic Med. Chem. Lett. 2013, 23, 3180–3185. [Google Scholar] [CrossRef] [PubMed]
- Nair, S.; Trummell, H.Q.; Rajbhandari, R.; Thudi, N.K.; Nozell, S.E.; Warram, J.M.; Willey, C.D.; Yang, E.S.; Placzek, W.J.; Bonner, J.A.; et al. Novel EGFR ectodomain mutations associated with ligand-independent activation and cetuximab resistance in head and neck cancer. PLoS ONE 2020, 15, e0229077. [Google Scholar] [CrossRef] [Green Version]
- Van Lehn, R.C.; Atukorale, P.U.; Carney, R.P.; Yang, Y.-S.; Stellacci, F.; Irvine, D.J.; Alexander-Katz, A. Effect of Particle Diameter and Surface Composition on the Spontaneous Fusion of Monolayer-Protected Gold Nanoparticles with Lipid Bilayers. Nano Lett. 2013, 13, 4060–4067. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Maeda, H.; Wu, J.; Sawa, T.; Matsumura, Y.; Hori, K. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: A review. J. Control. Release 2000, 65, 271–284. [Google Scholar] [CrossRef]
- Matsumura, Y.; Maeda, H. A new concept for macromolecular therapeutics in cancer chemotherapy: Mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res. 1986, 46, 6387–6392. [Google Scholar] [PubMed]
- Sindhwani, S.; Syed, A.M.; Ngai, J.; Kingston, B.R.; Maiorino, L.; Rothschild, J.; Macmillan, P.; Zhang, Y.; Rajesh, N.U.; Hoang, T.; et al. The entry of nanoparticles into solid tumours. Nat. Mater. 2020, 19, 566–575. [Google Scholar] [CrossRef]
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Egnuni, T.; Ingram, N.; Mirza, I.; Coletta, P.L.; McLaughlan, J.R. Evaluation of the Targeting and Therapeutic Efficiency of Anti-EGFR Functionalised Nanoparticles in Head and Neck Cancer Cells for Use in NIR-II Optical Window. Pharmaceutics 2021, 13, 1651. https://doi.org/10.3390/pharmaceutics13101651
Egnuni T, Ingram N, Mirza I, Coletta PL, McLaughlan JR. Evaluation of the Targeting and Therapeutic Efficiency of Anti-EGFR Functionalised Nanoparticles in Head and Neck Cancer Cells for Use in NIR-II Optical Window. Pharmaceutics. 2021; 13(10):1651. https://doi.org/10.3390/pharmaceutics13101651
Chicago/Turabian StyleEgnuni, Teklu, Nicola Ingram, Ibrahim Mirza, P. Louise Coletta, and James R. McLaughlan. 2021. "Evaluation of the Targeting and Therapeutic Efficiency of Anti-EGFR Functionalised Nanoparticles in Head and Neck Cancer Cells for Use in NIR-II Optical Window" Pharmaceutics 13, no. 10: 1651. https://doi.org/10.3390/pharmaceutics13101651
APA StyleEgnuni, T., Ingram, N., Mirza, I., Coletta, P. L., & McLaughlan, J. R. (2021). Evaluation of the Targeting and Therapeutic Efficiency of Anti-EGFR Functionalised Nanoparticles in Head and Neck Cancer Cells for Use in NIR-II Optical Window. Pharmaceutics, 13(10), 1651. https://doi.org/10.3390/pharmaceutics13101651