Recent progress in nanomedicine for enhanced cancer chemotherapy

Theranostics, Journal Year: 2021, Volume and Issue: 11(13), P. 6370 - 6392

Published: Jan. 1, 2021

As one of the most important cancer treatment strategies, conventional chemotherapy has substantial side effects and leads easily to failure. Therefore, exploring developing more efficient methods enhance is an urgently problem that must be solved. With development nanotechnology, nanomedicine showed a good application prospect in improving chemotherapy. In this review, we aim present discussion on significant research progress for enhanced First, increased enrichment drugs tumor tissues relying different targeting ligands promoting tissue penetration are summarized. Second, specific subcellular organelle-targeted discussed. Next, combinational strategies reverse multidrug resistance (MDR) improve effective intracellular concentration therapeutics Furthermore, advantages combination therapy emphasized. Finally, discuss major problems facing therapeutic chemotherapy, propose possible future directions field.

Language: Английский

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A human-airway-on-a-chip for the rapid identification of candidate antiviral therapeutics and prophylactics

Nature Biomedical Engineering, Journal Year: 2021, Volume and Issue: 5(8), P. 815 - 829

Published: May 3, 2021

Language: Английский

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Multiorgan-on-a-Chip: A Systemic Approach To Model and Decipher Inter-Organ Communication

Trends in biotechnology, Journal Year: 2021, Volume and Issue: 39(8), P. 788 - 810

Published: Feb. 2, 2021

Multiorgan-on-a-chip (multi-OoC) devices, by supporting cross-organ communication, allow the study of multiorgan processes and modeling systemic diseases.Multi-OoC approaches provide new insights that would be lost using single-OoC models.Various coupling configurations have been proposed for building multi-OoC platforms, these present different levels user-friendliness.Multi-OoC platforms potential to transform medical research opening avenues understanding diseases developing personalized treatments.To further emulate complexity human system in vivo, key elements immune, nervous, vascular systems are being integrated into models.The next generation multi-OoCs will incorporate multimodal real-time readouts form on-chip chemical, physical, molecular sensors, as well online multiomic analysis. great redefine way which health is conducted. After briefly reviewing need comprehensive models with a dimension, we highlight scenarios advantageous. We overview existing including body-on-a-chip devices modular involving interconnected organ-specific modules. how can unique information not accessible models. Finally, discuss remaining challenges realization their worldwide adoption. anticipate technology metamorphose biology medicine providing holistic treating multisystem diseases. Interactions between multiple organs essential ensure proper physiological functioning body. Although physically separated communication mediated via blood lymph circulation various signals (soluble factors, exosomes, cells, etc.) maintain overall viability homeostasis. For example, journey orally ingested substances (nutrients, chemicals, drugs, orchestrated involves through specific sequence each organ has function: small intestine absorbs (digested) substances, liver metabolizes them, they then delivered target circulation, kidney excretes corresponding waste products. This complex process absorption/distribution/metabolism/excretion/toxicity (ADMET; see Glossary) affects fate, distribution, efficacy (if applicable), possible toxicity exogenous (e.g., food, additives, environmental pollutants) [1.Cheng F. et al.AdmetSAR: source free tool assessment chemical ADMET properties.J. Chem. Inf. Model. 2012; 52: 3099-3105Crossref PubMed Scopus (725) Google Scholar] unwanted side-effects secondary tissues. In addition, many functions body depend on regulatory pathways hormonal feedback loops involve endocrine system. The reproductive system, comprises tissues, relies control peripheral Similarly, Langerhans islets pancreas secrete insulin promotes glucose uptake liver. Together, this deciphering emulating temporal involved functions. As direct consequence, such sepsis, osteoarthritis, gout, infertility, neurodegenerative organs, must therefore pursued accurately model them. identifying biomarkers fluids diagnostic purposes. instance, tumor tissues release molecules (miRNA, circulating DNA, peptides, etc.), tumor-derived extracellular vesicles (tdEVs), cells (CTCs) play central role cancer metastasis patient management [2.Rikkert L.G. al.Cancer-ID: toward identification blood.Front. Oncol. 2020; 10: 608Crossref (1) Scholar,3.Heitzer E. al.Current future perspectives liquid biopsies genomics-driven oncology.Nat. Rev. Genet. 2019; 20: 71-88Crossref (304) Scholar]. All examples illustrate it include depicted Figure 1, most commonly achieved animal Nevertheless, vivo suffer from numerous limitations: high experimental costs, limited throughput, ethical concerns, differences genetic background. More importantly, exhibit large terms drug effects and/or disease phenotypes compared humans, explains frequent failure clinical trials [4.Low L.A. al.Organs-on-chips: decade.Nat. Drug Discov. (Published September 10, 2020. https://doi.org/10.1038/s41573-020-0079-3)Crossref (9) Overall, animals do analysis inter-organ crosstalk, determination quantitative pharmacokinetics (PK), or prediction parameters, recently highlighted [5.Ingber D.E. Is time reviewer 3 request chip experiments instead validation studies?.Adv. Sci. 72002030Crossref (22) Therefore, advanced vitro incorporating dimension developed faithfully pathophysiology. Previous efforts employed either conditioned medium cocultures Transwell platforms. However, use volumes liquid, slow low-concentration signaling factors diluted, altogether hampers studying cellular communication. Furthermore, culture entirely static, precludes emulation dynamic application controlled cell biochemical physical stimuli. Using microfluidic format solve some issues offering sub-milliliter volumes, culture, exquisite spatiotemporal over parameters cell/tissue vicinity. cell–cell studied microdevices under continuous flow chambers porous membranes [6.Chung H.H. al.Use tissue barrier co-culture models.Lab Chip. 2018; 18: 1671-1689Crossref Scholar], pillar arrays [7.Lembong J. al.A fluidic platform spatially patterned growth, differentiation, cocultures.Tissue Eng. Part A. 24: 1715-1732Crossref (12) channels [8.Zhou Q. al.Liver injury-on-a-chip: co-cultures biosensors monitoring during injury.Lab 2015; 15: 4467-4478Crossref Building cultures, organ-on-a-chip (OoC) aim mimic architecture function an combining 3D bioengineered constructs cell-laden hydrogels [9.Patrício S.G. al.Freeform printing viscoelastic matrix.Biofabrication. 12035017Crossref (2) differentiated epithelium [10.van den Broek L.J. al.Progress prospectives skin-on-chip development emphasis types technical challenges.Stem Cell Rep. 2017; 13: 418-429Crossref (38) Scholar,11.Schimek K. al.Bioengineering full-thickness skin equivalent 96-well insert substance permeation studies applications.Bioengineering (Basel). 5: 43Crossref (11) multicellular spheroids [12.Nashimoto Y. al.Integrating perfusable networks three-dimensional device.Integr. Biol. (Camb.). 9: 506-518Crossref organoids [13.Rajan S.A.P. al.Probing prodrug metabolism reciprocal humanized multi-tissue platform.Acta Biomater. 106: 124-135Crossref (8) Scholar, 14.Achberger al.Merging organoid generate multi-layer retina-on-a-chip platform.Elife. 8Crossref (7) 15.Picollet-D'hahan N. al.Deciphering cell-intrinsic properties: issue robust production.Trends Biotechnol. 35: 1035-1048Abstract Full Text PDF (0) Scholar]), ex explants) [16.Schwerdtfeger Tobet S.A. From organotypic body-on-a-chip: A neuroendocrine perspective.J. Neuroendocrinol. 31e12650Crossref (3) 17.McLean I.C. al.Powering systems.Lab 1399-1410Crossref 18.Shim S. al.Two-way chip: tumor–lymph node interaction.Lab 19: 1013-1026Crossref recellularized scaffolds [19.Wang microengineered collagen scaffold generating polarized crypt-villus intestinal epithelium.Biomaterials. 128: 44-55Crossref (116) bioprinted [20.Yu Choudhury D. Microfluidic bioprinting models.Drug Today. 1248-1257Crossref (35) microfabricated structures [21.Hinman S.S. al.Microphysiological design: simplicity elegance.Curr. Opin. Biomed. 94-102Crossref possibly active stimulation (electrical, biochemical, mechanical) [22.Kaarj Yoon J.-Y. Methods delivering mechanical stimuli organ-on-a-chip.Micromachines 700Crossref 23.Gaio al.Cytostretch, organ-on-chip platform.Micromachines 2016; 7: 120Crossref (16) 24.Visone R. microscale biomimetic electro-mechanical cardiac microtissues.APL Bioeng. 2046102Crossref OoC field blossoming decade, virtually all barriers Scholar,25.Mastrangeli M. al.Building blocks European roadmap.ALTEX. 36: 481-492Crossref (4) Scholar,26.Mastrangeli al.Organ-on-chip development: towards roadmap organs-on-chip.ALTEX. 650-668Crossref These revolutionizing experimentation hold promise reducing testing. based single type tissue, lack both major recent breakthrough, modeled device (Figure 2). detailed Box two realize platforms: units integration one plate (multi-OoC plates).Box 1Multi-OoC Typology ApplicationsMulti-OoC classified main distinct types, typology referring engineering approach used realization, namely connection plate.First, connected capillary tubing motherboard reproduce interactions more IA). allows reconfiguration supports individual vascularized microvasculature endothelial cells. modules first established matured before other. By contrast, IB) integrate single-plate at locations, where act vascular-like support second much akin human-on-a-chip paradigm IC). Multi-OoC plates compact user-friendly, require manual cumbersome connection, limit risks leakage, and, cases, actuation They also advantageous minimizing total recirculation volume (see section 'Circulation Medium' text). vascularization less trivial, following (section .Organ Models. text) may challenging.These arguably better suited former 'Lego-like' likely preferred fundamental academic setting. offer only low-to-moderate ideal preclinical, toxicity, tests. turnkey plate-based higher hence appropriate therapeutic targets, selection optimization candidates.Figure ISchematic Representation Two Main Approaches Developing Systems.Show full caption(A) Through organ, (B); (C) integrating plate, line philosophy.View Large Image ViewerDownload Hi-res image Download (PPT) plate. First, challenging. candidates. review combinations best particular applications. Specific areas brings superior set considered provided approach. Selected past 5 years summarized Table 1 (Key Table).Table 1Key Table. Overview Recently Reported PlatformsaAbbreviations: A549, non-small lung cells; AA, amino acid; ALI, air–liquid Interface; AMSCs, airway stromal mesenchymal (donor derived); APCs, antigen-presenting BCA, bicinchoninic BF, bovine fetuin; BSA, serum albumin; Caco-2, heterogeneous epithelial colorectal adenocarcinoma ECM, matrix; FBS, fetal serum; Fob1.19, osteoblast hA, astrocytes; HA, hyaluronic HA-1800, astrocyte 16HBE, bronchial HBMECs, brain microvascular HBVPs, pericytes; HCT-116, colon HepaRG, hepatic stem HEPES, (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid) buffer; HepG2/C3a, hepatocellular carcinoma hHSteC, stellate HL60, leukemia hLSMECs, sinusoidal HM, microglial; HMVEC-L, HNC, neural hPCF, primary fibroblasts; hRPTECs, renal proximal tubule HUVECs, umbilical vein Hw36, hepatocytes; Kupffer macrophages; IFN, interferon; IL, interleukin; L-02, hepatocyte LC, chromatography; LDH, lactate dehydrogenase; MBA-MD-231, breast MCF-7, MDCK, Madin–Darby canine MEA, measurements neurons Maestro™ MEA (Multi Electrode Arrays) system; NHBE, normal bronchial/tracheal NPCs, progenitor NTera2/cl.D1, pluripotent testicular embryonal PEEK, polyetheretherketone; PEGDA, poly(ethyleneglycol) diacrylate; PET, polyethylene terephthalate; PI, propidium iodide; PSF, polysulfone; RPTECs, RPTEC/TERT-1, immortalized SSCs, spermatogonial THP-1, monocyte TIG-121, diploid fibroblast Treg, T cell; UC, ulcerative colitis. lines preceded (GFP) (RFP) indicate engineered express GFP/RFP.,bReferences [13,18,27–35,37,39,40,43–47,50,51,53,54,88,93,94] found reference list end paper.a Abbreviations: GFP/RFP.b References Scholar,18.Shim Scholar,27.Bovard lung/liver-on-a-chip acute chronic studies.Lab 3814-3829Crossref 28.Kimura H. al.An intestine–liver pharmacokinetic studies.J. Lab. Autom. 265-273Crossref (62) 29.Oleaga C. al.Investigation effect off-target cardiotoxicity multi-organ system.Biomaterials. 182: 176-190Crossref 30.Materne E.-M. neurospheres equivalents long-term testing.J. 205: 36-46Crossref (97) 31.Hübner al.Simultaneous evaluation anti-EGFR-induced tumour adverse model.Sci. 8: 15010Crossref 32.Kim al.96-well format-based parallel interconnection spheroids.J. 274-282Crossref (47) 33.Ong L.J.Y. al.Self-aligning Tetris-like (TILE) mimicking interactions.Lab 2178-2191Crossref 34.Satoh T. multi-throughput multi-organ-on-a-chip formatted pneumatic pressure-driven platform.Lab 115-125Crossref 35.Theobald al.In metabolic activation vitamin D3 multi-compartment liver–kidney platform.Sci. 4616Crossref Scholar,37.Chong L.H. liver-immune coculture array predicting drug-induced sensitization.Lab 3239-3250Crossref Scholar,39.Edington C.D. al.Interconnected microphysiological pharmacology studies.Sci. 4530Crossref (165) Scholar,40.Herland al.Quantitative responses drugs fluidically coupled chips.Nat. 4: 421-436Crossref (64) Scholar,43.Loskill P. al.μOrgano: Lego®-like plug & multi-organ-chips.PLoS One. 10e0139587Crossref (18) 44.Esch M.B. al.Modular, pumpless GI tract tissue.Lab 16: 2719-2729Crossref 45.Maschmeyer I. four-organ-chip intestine, liver, equivalents.Lab 2688-2699Crossref 46.Ramme A.P. al.Autologous induced cell-derived four-organ-chip.Future OA. 5FSO413Crossref (20) 47.Trapecar al.Gut–liver physiomimetics reveal paradoxical modulation IBD-related Inflammation short-chain fatty acids.Cell Syst. 10 (e9): 223-239Abstract (27) Scholar,50.Bauer al.Functional pancreatic on-a-chip: novel 2 diabetes 14620Crossref Scholar,51.Xiao 28-day menstrual cycle.Nat. Commun. 814584Crossref (175) Scholar,53.Kong cells.Oncotarget. 78421-78432Crossref Scholar,54.Xu Z. al.Design construction microenvironment metastasis.ACS Appl. Mater. Interfaces. 25840-25847Crossref Scholar,88.Aleman Skardal multi-site metastasis-on-a-chip assessing metastatic preference cells.Biotechnol. 116: 936-944Crossref (33) Scholar,93.Skardal reductionist progression screening.Biotechnol. 113: 2020-2032Crossref (90) Scholar,94.Skardal al.Multi-tissue three-tissue 8837Crossref (189) paper. Toxicity closely linked purposes least other (target) organ. examine inhaled aerosols combined [27.Bovard 2C). pharmacological typically added minimal liver–target absorption [28.Kimura Alternatively, when undesired treatment evaluated, expected, (nephrotoxicity), heart (cardiotoxicity) [29.Oleaga (neurotoxicity) [30.Materne long-ter

Language: Английский

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Bioprinting for the Biologist

Cell, Journal Year: 2021, Volume and Issue: 184(1), P. 18 - 32

Published: Jan. 1, 2021

Language: Английский

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Is it Time for Reviewer 3 to Request Human Organ Chip Experiments Instead of Animal Validation Studies?

Advanced Science, Journal Year: 2020, Volume and Issue: 7(22)

Published: Oct. 12, 2020

For the past century, experimental data obtained from animal studies have been required by reviewers of scientific articles and grant applications to validate physiological relevance in vitro results. At same time, pharmaceutical researchers regulatory agencies recognize that results preclinical models frequently fail predict drug responses humans. This Progress Report reviews recent advances human organ-on-a-chip (Organ Chip) microfluidic culture technology, both with single Organ Chips fluidically coupled "Body-on-Chips" platforms, which demonstrate their ability recapitulate physiology disease states, as well patient clinically relevant pharmacokinetic exposures, higher fidelity than other or studies. These findings raise question whether continuing require testing for publication funding still makes ethical sense, if more physiologically Chip might better serve this purpose. issue is addressed article context history field, advantages disadvantages approaches versus are discussed should be considered wider research community.

Language: Английский

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Emerging Technologies in Multi‐Material Bioprinting

Advanced Materials, Journal Year: 2021, Volume and Issue: 33(49)

Published: Oct. 1, 2021

Bioprinting, within the emerging field of biofabrication, aims at fabrication functional biomimetic constructs. Different 3D bioprinting techniques have been adapted to bioprint cell-laden bioinks. However, single-material oftentimes fail reproduce complex compositions and diversity native tissues. Multi-material as an approach enables heterogeneous multi-cellular constructs that replicate their host microenvironments better than approaches. Here, modalities are reviewed, being multi-material is discussed, advantages challenges, encompassing both custom-designed commercially available technologies analyzed. A perspective how opens up new opportunities for tissue engineering, model therapeutics development, personalized medicine offered.

Language: Английский

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Biofabrication of natural hydrogels for cardiac, neural, and bone Tissue engineering Applications

Bioactive Materials, Journal Year: 2021, Volume and Issue: 6(11), P. 3904 - 3923

Published: April 16, 2021

Natural hydrogels are one of the most promising biomaterials for tissue engineering applications, due to their biocompatibility, biodegradability, and extracellular matrix mimicking ability. To surpass limitations conventional fabrication techniques recapitulate complex architecture native structure, natural being constructed using novel biofabrication strategies, such as textile three-dimensional bioprinting. These innovative play an enormous role in development advanced scaffolds various applications. The progress, advantages, shortcomings emerging highlighted this review. Additionally, applications biofabricated cardiac, neural, bone discussed well.

Language: Английский

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Ectopic Lymphoid Follicle Formation and Human Seasonal Influenza Vaccination Responses Recapitulated in an Organ‐on‐a‐Chip

Advanced Science, Journal Year: 2022, Volume and Issue: 9(14)

Published: March 14, 2022

Lymphoid follicles (LFs) are responsible for generation of adaptive immune responses in secondary lymphoid organs and form ectopically during chronic inflammation. A human model ectopic LF formation will provide a tool to understand development an alternative non-human primates preclinical evaluation vaccines. Here, it is shown that primary blood B- T-lymphocytes autonomously assemble into LFs when cultured 3D extracellular matrix gel within one channel two-channel organ-on-a-chip microfluidic device. Superfusion via parallel separated by microporous membrane required prevents lymphocyte autoactivation. These germinal center-like contain B cells expressing Activation-Induced Cytidine Deaminase exhibit plasma cell differentiation upon activation. To explore their utility seasonal vaccine testing, autologous monocyte-derived dendritic integrated Chips. The chips demonstrate improved antibody split virion influenza vaccination compared 2D cultures, which enhanced squalene-in-water emulsion adjuvant, this accompanied increases size number. When inoculated with commercial vaccine, production anti-hemagglutinin IgG observed, as well secretion cytokines similar vaccinated humans over clinically relevant timescales.

Language: Английский

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Vaginal microbiome-host interactions modeled in a human vagina-on-a-chip

Microbiome, Journal Year: 2022, Volume and Issue: 10(1)

Published: Nov. 26, 2022

Abstract Background A dominance of non-iners Lactobacillus species in the vaginal microbiome is optimal and strongly associated with gynecological obstetric health, while presence diverse obligate or facultative anaerobic bacteria a paucity species, similar to communities found bacterial vaginosis (BV), considered non-optimal adverse health outcomes. Various therapeutic strategies are being explored modulate composition microbiome; however, there no human model that faithfully reproduces epithelial microenvironment for preclinical validation potential therapeutics testing hypotheses about epithelium-microbiome interactions. Results Here, we describe an organ-on-a-chip (organ chip) microfluidic culture mucosa (vagina lined by hormone-sensitive, primary epithelium interfaced underlying stromal fibroblasts, which sustains low physiological oxygen concentration lumen. We show Vagina Chip can be used assess colonization L. crispatus consortia as well Gardnerella vaginalis- containing consortia, measure host innate immune responses. Co-culture growth on-chip was accompanied maintenance cell viability, accumulation D- L-lactic acid, physiologically relevant pH, down regulation proinflammatory cytokines. In contrast, co-culture G. vagina chip resulted injury, rise upregulation Conclusion This study demonstrates applying organ technology create better understand interactions between tissues, evaluate safety efficacy live biotherapeutics products.

Language: Английский

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Bio-Inspired Nanomaterials for Micro/Nanodevices: A New Era in Biomedical Applications

Micromachines, Journal Year: 2023, Volume and Issue: 14(9), P. 1786 - 1786

Published: Sept. 18, 2023

Exploring bio-inspired nanomaterials (BINMs) and incorporating them into micro/nanodevices represent a significant development in biomedical applications. Nanomaterials, engineered to imitate biological structures processes, exhibit distinctive attributes such as exceptional biocompatibility, multifunctionality, unparalleled versatility. The utilization of BINMs demonstrates potential diverse domains micro/nanodevices, encompassing biosensors, targeted drug delivery systems, advanced tissue engineering constructs. This article thoroughly examines the various BINMs, including those originating from proteins, DNA, biomimetic polymers. Significant attention is directed toward these entities subsequent ramifications that arise. review explores biomimicry’s structure–function correlations. Synthesis mosaics include bioprocesses, biomolecules, natural structures. These nanomaterials’ interfaces use functionalization geometric adaptations, transforming delivery, nanobiosensing, organ-on-chip cancer-on-chip models, wound healing dressing mats, antimicrobial surfaces. It provides an in-depth analysis existing challenges proposes prospective strategies improve efficiency, performance, reliability devices. Furthermore, this study offers forward-thinking viewpoint highlighting avenues for future exploration advancement. objective effectively utilize maximize application progression thereby propelling rapidly developing field its promising future.

Language: Английский

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