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Biomimetic bright optotheranostics for metastasis monitoring and multimodal image-guided breast cancer therapeutics
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Orientador(es)
Resumo(s)
Nanoparticle formulations blending optical imaging contrast agents and therapeutics have been a cornerstone of preclinical theranostic applications. However, nanoparticle-based theranostics clinical translation faces challenges on reproducibility, brightness, photostability, biocompatibility, and selective tumor targeting and penetration. In this study, we integrate multimodal imaging and therapeutics within cancer cell-derived nanovesicles, leading to biomimetic bright optotheranostics for monitoring cancer metastasis. Upon NIR light irradiation, the engineered optotheranostics enables deep visualization and precise localization of metastatic lung, liver, and solid breast tumors along with solid tumor ablation. Metastatic cell-derived nanovesicles (∼80 ± 5 nm) are engineered to encapsulate imaging (emissive organic dye and gold nanoparticles) and therapeutic agents (anticancer drug doxorubicin and photothermally active organic indocyanine green dye). Systemic administration of biomimetic bright optotheranostic nanoparticles shows escape from mononuclear phagocytic clearance with (i) rapid tumor accumulation (3 h) and retention (up to 168 h), (ii) real-time monitoring of metastatic lung, liver, and solid breast tumors and (iii) 3-fold image-guided solid tumor reduction. These findings are supported by an improvement of X-ray, fluorescence, and photoacoustic signals while demonstrating a tumor reduction (201 mm3) in comparison with single therapies that includes chemotherapy (134 mm3), photodynamic therapy (72 mm3), and photothermal therapy (88 mm3). The proposed innovative platform opens new avenues to improve cancer diagnosis and treatment outcomes by allowing the monitorization of cancer metastasis, allowing the precise cancer imaging, and delivering synergistic therapeutic agents at the solid tumor site.
Descrição
Funding Information: R.P. would like to thank the Director and the School of Biochemical Engineering, Indian Institute of Technology (BHU), Varanasi for the support during preparation of this manuscript. R.P. also thanks the support of Tufts University , J.C. and B.B.M. acknowledge the European Research Council (Grant Agreement 848325 ). B.B.M., H.I.K., H.Z. and M.G. contributed equally to this project. We thank Dr. Gupta for critical reading of the manuscript and discussions on tumor imaging and therapeutic data. M.G. and G.C.K. thank support from NCCS , Pune and KIIT . H.I.K., H.Z., J.X. and J.F.L would like to thank the support from the University at Buffalo . Funding Information: J.C. is a co-founder and shareholder of TargTex S.A – Targeted Therapeutics for Glioblastoma Multiforme. J.C. is a member of the Global Burden Disease (GBD) consortium from Institute for Health Metrics and Evaluation (IHME), University of Washington (US). All the other authors declare no conflict of interest.R.P. would like to thank the Director and the School of Biochemical Engineering, Indian Institute of Technology (BHU), Varanasi for the support during preparation of this manuscript. R.P. also thanks the support of Tufts University, J.C. and B.B.M. acknowledge the European Research Council (Grant Agreement 848325). B.B.M. H.I.K. H.Z. and M.G. contributed equally to this project. We thank Dr. Gupta for critical reading of the manuscript and discussions on tumor imaging and therapeutic data. M.G. and G.C.K. thank support from NCCS, Pune and KIIT. H.I.K. H.Z. J.X. and J.F.L would like to thank the support from the University at Buffalo. Publisher Copyright: © 2024 The Author(s)
Palavras-chave
Biomimetic Bright optotheranostics Metastasis Multimodal imaging and therapy Solid tumor Pharmaceutical Science SDG 3 - Good Health and Well-being