Programmable Chemotherapy and Immunotherapy against Breast Cancer Guided by Multiplexed Fluorescence Imaging in the Second Near‐Infrared Window

Combined chemotherapy and immunotherapy have demonstrated great potential in cancer treatment. However, it is difficult to provide clear information of the pharmacokinetics and pharmacodynamics of chemodrugs and transplanted immune cells in vivo by traditional approaches, resulting in inadequate therapy. Here, a multiplexed intravital imaging strategy by using fluorescence in the second near-infrared window (NIR-II) is first developed to visualize the two events of chemotherapy and immunotherapy in vivo, so that a combinational administration is programed to improve the therapeutical effects against a mouse model of human breast cancer. In detail, Ag2 Se quantum dots (QDs) (λEm = 1350 nm) loaded with stromal-cell-derived factor-1α (SDF-1α) and chemodrug doxorubicin (DOX) are first administrated to deliver the SDF-1α and DOX to the tumor site. After their arrival, monitored by Ag2 Se QD fluorescence, natural killer (NK)-92 cells labeled with Ag2 S QDs (λEm = 1050 nm) are intravenously injected so that the cells are recruited to the tumor by the chemotaxis of SDF-1α, which is visualized by Ag2 S QD fluorescence. Such an imaging approach allows simultaneous evaluation of the behaviors of individual injections in vivo, and facilitates optimized administration regimens, resulting in enhanced tumor inhibition.

[1]  S. Rosenberg,et al.  Adoptive cell transfer: a clinical path to effective cancer immunotherapy , 2008, Nature Reviews Cancer.

[2]  Xiaoming Li,et al.  Epitaxial seeded growth of rare-earth nanocrystals with efficient 800 nm near-infrared to 1525 nm short-wavelength infrared downconversion photoluminescence for in vivo bioimaging. , 2014, Angewandte Chemie.

[3]  J. Frangioni.  In vivo near-infrared fluorescence imaging. , 2003, Current opinion in chemical biology.

[4]  M. Ng,et al.  Immune surveillance by mast cells during dengue infection promotes natural killer (NK) and NKT-cell recruitment and viral clearance , 2011, Proceedings of the National Academy of Sciences.

[5]  P. Johnston,et al.  Cancer drug resistance: an evolving paradigm , 2013, Nature Reviews Cancer.

[6]  W. Scheper,et al.  PEGylated nanoparticles bind to and alter amyloid-beta peptide conformation: toward engineering of functional nanomedicines for Alzheimer's disease. , 2012, ACS nano.

[7]  J. Loscalzo,et al.  SDF-1α in glycan nanoparticles exhibits full activity and reduces pulmonary hypertension in rats. , 2013, Biomacromolecules.

[8]  E. Haura,et al.  HDAC Inhibitors Enhance T-Cell Chemokine Expression and Augment Response to PD-1 Immunotherapy in Lung Adenocarcinoma , 2016, Clinical Cancer Research.

[9]  Michael S Strano,et al.  M13 phage-functionalized single-walled carbon nanotubes as nanoprobes for second near-infrared window fluorescence imaging of targeted tumors. , 2012, Nano letters.

[10]  Qiangbin Wang,et al.  Real-Time Monitoring Surface Chemistry-Dependent In Vivo Behaviors of Protein Nanocages via Encapsulating an NIR-II Ag2S Quantum Dot. , 2015, ACS nano.

[11]  Yan Zhang,et al.  Near-infrared photoluminescent Ag2S quantum dots from a single source precursor. , 2010, Journal of the American Chemical Society.

[12]  A. Epstein,et al.  Chemokines, costimulatory molecules and fusion proteins for the immunotherapy of solid tumors. , 2011, Immunotherapy.

[13]  Kevin Welsher,et al.  Deep-tissue anatomical imaging of mice using carbon nanotube fluorophores in the second near-infrared window , 2011, Proceedings of the National Academy of Sciences.

[14]  D. Gabrilovich.  Combination of chemotherapy and immunotherapy for cancer: a paradigm revisited. , 2007, The Lancet. Oncology.

[15]  Zhe Zhang,et al.  A high quantum yield molecule-protein complex fluorophore for near-infrared II imaging , 2017, Nature Communications.

[16]  Shuo Diao,et al.  In vivo fluorescence imaging with Ag2S quantum dots in the second near-infrared region. , 2012, Angewandte Chemie.

[17]  Yan Zhang,et al.  Tracking of Transplanted Human Mesenchymal Stem Cells in Living Mice using Near‐Infrared Ag2S Quantum Dots , 2014 .

[18]  Guangcun Chen,et al.  Engineered Multifunctional Nanomedicine for Simultaneous Stereotactic Chemotherapy and Inhibited Osteolysis in an Orthotopic Model of Bone Metastasis , 2017, Advanced materials.

[19]  O. Scherman,et al.  Triply triggered doxorubicin release from supramolecular nanocontainers. , 2012, Biomacromolecules.

[20]  S. Rosenberg,et al.  Adoptive cell transfer as personalized immunotherapy for human cancer , 2015, Science.

[21]  Yan Zhang,et al.  In vivo real-time visualization of tissue blood flow and angiogenesis using Ag2S quantum dots in the NIR-II window. , 2014, Biomaterials.

[22]  M. Bawendi,et al.  Selection of Quantum Dot Wavelengths for Biomedical Assays and Imaging , 2003, Molecular Imaging.

[23]  B. Wall,et al.  Rare-earth-doped biological composites as in vivo shortwave infrared reporters , 2013, Nature Communications.

[24]  Guosong Hong,et al.  Multifunctional in vivo vascular imaging using near-infrared II fluorescence , 2012, Nature Medicine.

[25]  J. Weiss,et al.  Successful immunotherapy with IL-2/anti-CD40 induces the chemokine-mediated mitigation of an immunosuppressive tumor microenvironment , 2009, Proceedings of the National Academy of Sciences.

[26]  Sangeeta N. Bhatia,et al.  Deep, noninvasive imaging and surgical guidance of submillimeter tumors using targeted M13-stabilized single-walled carbon nanotubes , 2014, Proceedings of the National Academy of Sciences.

[27]  J. G. Solé,et al.  1.3 μm emitting SrF2:Nd3+ nanoparticles for high contrast in vivo imaging in the second biological window , 2015, Nano Research.

[28]  F. Mami-Chouaib,et al.  Role of chemokines and chemokine receptors in shaping the effector phase of the antitumor immune response. , 2012, Cancer research.

[29]  M. C. Mancini,et al.  Bioimaging: second window for in vivo imaging. , 2009, Nature nanotechnology.

[30]  Zhuang Liu,et al.  Drug delivery with upconversion nanoparticles for multi-functional targeted cancer cell imaging and therapy. , 2011, Biomaterials.

[31]  Kathleen R. Cho,et al.  Epigenetic silencing of Th1 type chemokines shapes tumor immunity and immunotherapy , 2015, Nature.

[32]  Shuo Diao,et al.  A small-molecule dye for NIR-II imaging. , 2016, Nature materials.

[33]  Sanghwa Jeong,et al.  Imaging Depths of Near-Infrared Quantum Dots in First and Second Optical Windows , 2012, Molecular imaging.

[34]  J. Hanna,et al.  CXCL12 expression by invasive trophoblasts induces the specific migration of CD16- human natural killer cells. , 2003, Blood.

[35]  Shuo Diao,et al.  Through-skull fluorescence imaging of the brain in a new near-infrared window , 2014, Nature Photonics.

[36]  D. Hanahan,et al.  Hallmarks of Cancer: The Next Generation , 2011, Cell.

[37]  G. Bernardini,et al.  Multiple Myeloma Impairs Bone Marrow Localization of Effector Natural Killer Cells by Altering the Chemokine Microenvironment. , 2015, Cancer research.

[38]  Weiping Zou,et al.  Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy , 2017, Nature Reviews Immunology.

[39]  Qiangbin Wang,et al.  Facile Synthesis of Highly Photoluminescent Ag2Se Quantum Dots as a New Fluorescent Probe in the Second Near-Infrared Window for in Vivo Imaging , 2013 .

[40]  Dongmin Wu,et al.  Preoperative Detection and Intraoperative Visualization of Brain Tumors for More Precise Surgery: A New Dual-Modality MRI and NIR Nanoprobe. , 2015, Small.