Biomimetic hydrogel supporting baths as an alternative to initiate and maintain breast tumor-derived organoids culture

Funding Information: This work was supported by the European Research Council (ERC) Starting Grant (ERC‐StG‐2019‐848325 to João Conde) and (DAI/2021/14 to Jhenifer Oliveira) and the Fundação para a Ciência e Tecnologia FCT Grant (PTDC/BTM‐MAT/4738/2020 to João Conde) and (2022.07775.PTDC to Bárbara B. Mendes).publishersversionpublishe

Nanomedicine-based strategies to target and modulate the tumor microenvironment

Funding Information: The authors acknowledge financial support from Fundação para a Ciência e a Tecnologia / Ministério da Ciência, Tecnologia, e Ensino Superior in the framework of PhD grant 2020.06638.BD (to D.P.S.), and from the European Research Council grant agreement No 848325 (J.C. for the ERC Starting Grant). Funding Information: The authors acknowledge financial support from Funda??o para a Ci?ncia e a Tecnologia/ Minist?rio da Ci?ncia, Tecnologia, e Ensino Superior in the framework of PhD grant 2020.06638.BD (to D.P.S.), and from the European Research Council grant agreement No 848325 (J.C. for the ERC Starting Grant). None declared by authors. Publisher Copyright: © 2021 Elsevier Inc.The interest in nanomedicine for cancer theranostics has grown significantly over the past few decades. However, these nanomedicines need to overcome several physiological barriers intrinsic to the tumor microenvironment (TME) before reaching their target. Intrinsic tumor genetic/phenotypic variations, along with intratumor heterogeneity, provide different cues to each cancer type, making each patient with cancer unique. This brings additional challenges in translating nanotechnology-based systems into clinically reliable therapies. To develop efficient therapeutic strategies, it is important to understand the dynamic interactions between TME players and the complex mechanisms involved, because they constitute invaluable targets to dismantle tumor progression. In this review, we discuss the latest nanotechnology-based strategies for cancer diagnosis and therapy as well as the potential targets for the design of future anticancer nanomedicines.publishersversionpublishe

Machine learning for next-generation nanotechnology in healthcare

Funding: The authors acknowledge financial support from FCT Portugal in the framework of PhD grant 2020.06638.BD (to D.P.S.), and the European Research Council grant agreement 848325 (J. Conde for the ERC Starting Grant). T.R. is an Investigador Auxiliar supported by FCT Portugal (CEECIND/ 00684/2018).Nanotechnology for healthcare is coming of age, but automating the design of composite materials poses unique challenges. Although machine learning is supporting groundbreaking discoveries in materials science, new initiatives leveraging learned patterns are required to fully realize the promise of nanodelivery systems and accelerate development pipelines.publishersversionpublishe

Hydrogels for RNA delivery

Funding Information: This work was supported by the US National Institutes of Health grants R01CA200900, R01HL156362, R01HL159012 and R01HL162367 (to J.S.), the Lung Cancer Discovery Award from the American Lung Association (to J.S.), the Innovation Discovery Grants award from the Mass General Brigham (to J.S.), the European Research Council Starting Grant (ERC-StG-2019-848325 to J.C. and B.B.M.) and the Fundação para a Ciência e a Tecnologia FCT Grant (PTDC/BTM-MAT/4738/2020 to J.C.). Publisher Copyright: © 2023, Springer Nature Limited.RNA-based therapeutics have shown tremendous promise in disease intervention at the genetic level, and some have been approved for clinical use, including the recent COVID-19 messenger RNA vaccines. The clinical success of RNA therapy is largely dependent on the use of chemical modification, ligand conjugation or non-viral nanoparticles to improve RNA stability and facilitate intracellular delivery. Unlike molecular-level or nanoscale approaches, macroscopic hydrogels are soft, water-swollen three-dimensional structures that possess remarkable features such as biodegradability, tunable physiochemical properties and injectability, and recently they have attracted enormous attention for use in RNA therapy. Specifically, hydrogels can be engineered to exert precise spatiotemporal control over the release of RNA therapeutics, potentially minimizing systemic toxicity and enhancing in vivo efficacy. This Review provides a comprehensive overview of hydrogel loading of RNAs and hydrogel design for controlled release, highlights their biomedical applications and offers our perspectives on the opportunities and challenges in this exciting field of RNA delivery.publishersversionepub_ahead_of_prin

Biomimetic Ghost Nanomedicine-Based Optotheranostics for Cancer

Publisher Copyright: © 2024 The Authors. Published by American Chemical Society.Theranostic medicine combines diagnostics and therapeutics, focusing on solid tumors at minimal doses. Optically activated photosensitizers are significant examples owing to their photophysical and chemical properties. Several optotheranostics have been tested that convert light to imaging signals, therapeutic radicals, and heat. Upon light exposure, conjugated photosensitizers kill tumor cells by producing reactive oxygen species and heat or by releasing cancer antigens. Despite clinical trials, these molecularly conjugated photosensitizers require protection from their surroundings and a localized direction for site-specific delivery during blood circulation. Therefore, cell membrane biomimetic ghosts have been proposed for precise and safe delivery of these optically active large molecules, which are clinically relevant because of their biocompatibility, long circulation time, bypass of immune cell recognition, and targeting ability. This review focuses on the role of biomimetic nanoparticles in the treatment and diagnosis of tumors through light-mediated diagnostics and therapy, providing insights into their preclinical and clinical status.publishersversioninpres

Natural materials

The use of naturally occurring materials as scaffolds to support cell growth and proliferation significantly impacted the origin and progress of tissue engineering and regenerative medicine. However, the majority of these materials failed to provide adequate cues to guide cell differentiation toward the formation of new tissues. Over the past decade, a new generation of multifunctional and smart natural-based materials has been developed to provide biophysical and biochemical cues intended to specifically guide cell behavior. In this chapter, the use of extracellular matrix proteins and blood-derivatives intrinsic capacity to mimic the biophysical and biological characteristics of native tissues is reviewed. Furthermore, the design of a variety of nanostructures using the well-explored characteristics of nucleic acids is summarized. In the second section, the exploitation of supramolecular chemistry to create new dynamic functional hydrogels that mimic the extracellular matrix structure and/or composition is surveyed. Then, the incorporation of nanoelements in polymeric networks for the design of smart nanocomposite materials with tailored functionalities to guide cell behavior is introduced. Finally, the future perspectives in the development of new biomaterials for tissue engineering and regenerative medicine are presented.Te authors acknowledge the fnancial support of the European Union Framework Programme for Research and Innovation Horizon 2020, under the TEAMING grant agreement No 739572 – Te Discoveries CTR, Marie Skłodowska-Curie grant agreement No 706996 and European Research Council grant agreement No 726178; FCT (Fundação para a Ciência e a Tecnologia) and the Fundo Social Europeu através do Programa Operacional do Capital Humano (FSE/POCH) in the framework of Ph.D. grants PD/BD/113807/2015 (BBM) and PD/BD/129403/2017 (SMB), Post-Doc grant SFRH/ BPD/112459/2015 (RMD) and project SmarTendon (PTDC/NAN-MAT/30595/2017); Project NORTE01-0145-FEDER-000021 supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF

Bioinspired and biomimetic cancer-cell-derived membrane nanovesicles for preclinical tumor-targeted nanotheranostics

Funding Information: J.C. and B.M. acknowledge European Research Council grant agreement 848325 . R.P. would like to thank the Director, Indian Institute of Technology (BHU), Varanasi and the School of Biochemical Engineering, IIT (BHU) for support during preparation of this manuscript. We thank the Trident Diagnostics Center and staff for imaging and laser studies and NCCS, Pune for in vivo facilities. We would like to thank Prof. Rohit Srivastava and Dr. Sumit for their kind support. We extend our thanks to the School of Biotechnology and Kalinga Institute of Medical Sciences, KIIT, Institute of Eminence, Bhubaneswar. We dedicate this article to the memory of the late Prof. Sanjiv Sam Gambhir, a molecular imaging scientist. Figures/schemes were created with BioRender . Funding Information: J.C. and B.M. acknowledge European Research Council grant agreement 848325. R.P. would like to thank the Director, Indian Institute of Technology (BHU), Varanasi and the School of Biochemical Engineering, IIT (BHU) for support during preparation of this manuscript. We thank the Trident Diagnostics Center and staff for imaging and laser studies and NCCS, Pune for in vivo facilities. We would like to thank Prof. Rohit Srivastava and Dr. Sumit for their kind support. We extend our thanks to the School of Biotechnology and Kalinga Institute of Medical Sciences, KIIT, Institute of Eminence, Bhubaneswar. We dedicate this article to the memory of the late Prof. Sanjiv Sam Gambhir, a molecular imaging scientist. Figures/schemes were created with BioRender. J.C. and R.P. conceived the idea. M.G. G.C.K. R.P. and J.C. designed the experiments. M.G. G.C.K. R.P. and N.G. performed in vivo imaging and therapeutics studies. B.P. and E.H.A.W. conducted the western blots. B.P. and H.Q. performed the simulation studies. R.P. B.M. and J.C. wrote the paper. All authors contributed to final editing and multiple revisions of the present manuscript. J.C. is a co-founder and shareholder of TargTex S.A. R.P. is part of national and international patents related to lipid, gold, silica, and erythrocyte-based nanoparticles. Publisher Copyright: © 2023 The Author(s)Bioinspired cell-membrane-camouflaged nanohybrids have been proposed to enhance tumor targeting by harnessing their immune escape and self-recognition abilities. In this study, we introduce cancer-cell-derived membrane nanovesicles (CCMVs) integrated with gold nanorods (AuVNRs) in addition to therapeutic and imaging cargos such as doxorubicin and indocyanine green. This approach enhances targeted tumor imaging and enables synergistic chemo-phototherapeutics for solid tumors. CCMVs demonstrate significant tumor penetration and retention, serving as nanotheranostics with accessible surface biomarkers, biomimicking properties, and homologous targeting abilities. By evading uptake by the mononuclear phagocytic system, CCMVs can diffuse into the deep tumor core, leading to precise tumor reduction while preserving the surrounding healthy tissues. Notably, intravenous administration of these theranostic agents ensures biocompatibility, as evidenced by a survival period of approximately two months (up to 63 days) without any observed side effects. Our findings underscore the diagnostic and therapeutic potential of this biomimetic nanotheranostics platform.publishersversionepub_ahead_of_prin

Biomimetic bright optotheranostics for metastasis monitoring and multimodal image-guided breast cancer therapeutics

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)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.publishersversionpublishe

Nanodelivery of nucleic acids

Funding: This work was supported by the European Research Council (ERC) Starting Grant (ERC-StG-2019-848325 to J. Conde) and the Fundação para a Ciência e a Tecnologia FCT Grant (PTDC/BTM-MAT/4738/2020 to J. Conde). J.S. acknowledges US National Institute of Health (NIH) grants (R01CA200900, R01HL156362 and R01HL159012), the US DoD PRCRP Idea Award with Special Focus (W81XWH1910482), the Lung Cancer Discovery Award from the American Lung Association and the Innovation Discovery Grants award from the Mass General Brigham. H.L., D.Y. and X.Z. were supported by the National Key R&D Program of China (no. 2020YFA0710700), the National Natural Science Foundation of China (nos 21991132, 52003264, 52021002 and 52033010) and the Fundamental Research Funds for the Central Universities (no. WK2060000027).There is growing need for a safe, efficient, specific and non-pathogenic means for delivery of gene therapy materials. Nanomaterials for nucleic acid delivery offer an unprecedented opportunity to overcome these drawbacks; owing to their tunability with diverse physico-chemical properties, they can readily be functionalized with any type of biomolecules/moieties for selective targeting. Nucleic acid therapeutics such as antisense DNA, mRNA, small interfering RNA (siRNA) or microRNA (miRNA) have been widely explored to modulate DNA or RNA expression Strikingly, gene therapies combined with nanoscale delivery systems have broadened the therapeutic and biomedical applications of these molecules, such as bioanalysis, gene silencing, protein replacement and vaccines. Here, we overview how to design smart nucleic acid delivery methods, which provide functionality and efficacy in the layout of molecular diagnostics and therapeutic systems. It is crucial to outline some of the general design considerations of nucleic acid delivery nanoparticles, their extraordinary properties and the structure–function relationships of these nanomaterials with biological systems and diseased cells and tissues.publishersversionpublishe

Human-based nanocomposite cryogels for hemostatic and wound healing applications

In trauma surgery, a fast and effective hemostatic agent is crucial to prevent death. The current used hemostatic sponges are highly effective in stopping the hemorrhages, however they have a limited stability, shape memory, and biological functionality to induce an efficient regenerative healing after injury. Blood derivatives have attracted great attention as an inexpensive milieu of bioactive molecules (e.g., growth factors, cytokines), self-assembling scaffolding proteins (e.g., fibrinogen, fibronectin, vitronectin), and antimicrobial peptides (e.g., platelet factor-4) that have the ability to enhance angiogenesis, stem cell recruitment, and tissue regeneration. Among those, platelet lysate (PL) has attracted great attention as a milieu of supra-physiological doses of biomolecules that can be easily standardized. However, the current PL scaffolds showed limited stability and weak mechanical strength, which severely limits its performance as a bioinstructive and hemostatic biomaterial. Herein, we propose the use of aldehyde-functionalized CNC (a-CNC) that will be crosslinked through reversible Schiff base bonds established with the amine groups of PL proteins to produce a stable hemostatic cryogel for wound healing applications.EU’s H2020 programme for grant agreement 706996 and 739572 - The Discoveries CTR; FCT for SFRH/BPD/112459/2015, PD/BD/113807/2015, FOOD4CELLS (PTDC/CTM-BIO/4706/2014-POCI-01- 0145- FEDER 016716) and project NORTE-01-0145- FEDER-000021