Nanomaterials for cancer therapy: current progress and perspectives

Journal of Hematology & Oncology, Journal Year: 2021, Volume and Issue: 14(1)

Published: May 31, 2021

Abstract Cancer is a disease with complex pathological process. Current chemotherapy faces problems such as lack of specificity, cytotoxicity, induction multi-drug resistance and stem-like cells growth. Nanomaterials are materials in the nanorange 1–100 nm which possess unique optical, magnetic, electrical properties. used cancer therapy can be classified into several main categories. Targeting cells, tumor microenvironment, immune system, these nanomaterials have been modified for wide range therapies to overcome toxicity enhance drug capacity well bioavailability. Although number studies has increasing, approved nano-drugs not increased much over years. To better improve clinical translation, further research needed targeted delivery by nano-carriers reduce toxicity, permeability retention effects, minimize shielding effect protein corona. This review summarizes novel fabricated use, discusses current limitations obstacles that hinder translation from provides suggestions more efficient adoption therapy.

Language: Английский

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A Patient-Derived Glioblastoma Organoid Model and Biobank Recapitulates Inter- and Intra-tumoral Heterogeneity

Cell, Journal Year: 2019, Volume and Issue: 180(1), P. 188 - 204.e22

Published: Dec. 26, 2019

Language: Английский

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3D In Vitro Model (R)evolution: Unveiling Tumor–Stroma Interactions

Trends in cancer, Journal Year: 2020, Volume and Issue: 7(3), P. 249 - 264

Published: Nov. 19, 2020

Complex tumor–stroma interactions, a key feature of most solid tumors, drive tumor progression, metastasis, and drug resistance, ultimately lead to treatment failure.Clinically relevant 3D in vitro models are necessary recapitulate the complex interactions between stromal cells, provide tools better understand molecular mechanisms as well for testing anticancer therapies.Novel bioengineered models, organoid systems, microfabrication technologies, such bioprinting, have delivered innovations towards more advanced platforms modeling vitro. The microenvironment which malignant cells grow is crucial cancer progression. physical biochemical characteristics this niche involved controlling cell differentiation, proliferation, invasion, metastasis. It therefore essential how interact communicate with their surrounding tissue – so-called stroma interplay regulates disease To mimic (TME), widely used because they can incorporate different patient-derived tissues/cells allow longitudinal readouts, thus permitting deeper understanding interactions. These excellent bridge gap oversimplified 2D systems unrepresentative animal models. We present an overview state-of-the-art studying focus on why TME target therapy. composition (TME, see Glossary) major factors that aggravate growth leading poor clinical outcomes [1.Avnet S. et al.Pre-clinical interaction mesenchymal induction stemness.Front. Oncol. 2019; 9: 305Crossref PubMed Scopus (9) Google Scholar, 2.Mitchell M.J. al.Engineering sciences oncology: challenges opportunities.Nat. Rev. Cancer. 2017; 17: 659-675Crossref (132) 3.Asghar W. microenvironments 3-D models.Mater. Today. 2015; 18: 539-553Crossref (168) 4.Langhans S.A. Three-dimensional culture discovery repositioning.Front. Pharmacol. 2018; 6Crossref (370) 5.Rodenhizer D. al.The current landscape models: what hallmarks accessible discovery?.Adv. Healthc. Mater. 7e1701174Crossref (31) Scholar]. There increasing evidence activated disease-defining factor, highlighting it important player invasion/extravasation, migration, angiogenesis, resistance [6.Mcmillin D.W. role tumour-stromal modifying response: Drug Discov. 2013; 12: 217-228Crossref (282) Scholar,7.Maman Witz I.P. A history exploring context.Nat. 359-376Crossref (144) Scholar], stem maintenance [8.Batlle E. Clevers H. Cancer revisited.Nat. Med. 23: 1124-1134Crossref (838) immunosurveillance evasion Scholar,9.De Palma M. al.Microenvironmental regulation tumour angiogenesis.Nat. 457-474Crossref (627) Scholar,10.Valkenburg K.C. al.Targeting improve therapy.Nat. Clin. 15: 366-381Crossref stroma, nonneoplastic part TME, composed abundant extracellular matrix (ECM) multiple support [2.Mitchell including cancer-associated fibroblasts (CAFs), endothelial pericytes, immune [such lymphocytes, neutrophils, dendritic (DCs), monocytes] prevalent types (Figure 1). Other less include myeloid-derived suppressor (MDSCs) (MSCs) [7.Maman platelets [9.De Scholar,11.Yan Jurasz P. microenvironment: from tumors leukemia.Biochim. Biophys. Acta, Mol. Cell Res. 2016; 1863: 392-400Crossref (90) actively among themselves, ECM by secreting chemokines, (GFs), enzymes, vesicles, miRNAs regulate expression genes proteins influence metabolic pathways related [12.Ramamonjisoa N. Ackerstaff Characterization non-invasive preclinical imaging.Front. 7: 28-37Crossref (45) As such, some either promote or suppress depending upon cellular context [13.Bellomo C. al.Transforming factor β regulator stemness metastasis.Br. J. 115: 761-769Crossref (109) Hence, much has been accurately vivo. In field research, especially drugs, many experiments still performed cocultures, xenografts, syngeneic mouse Nevertheless, too simple unable complexity dynamic TME. Cells flat plastic surface monolayer, result loss signaling changes responses stimuli [14.Duval K. al.Modeling physiological events vs. culture.Physiology. 32: 266-277Crossref (478) 15.Mabry K.M. al.Microarray analyses quantify advantages hydrogel maintaining native valvular interstitial phenotype.Biomaterials. 74: 31-41Crossref (57) 16.Melissaridou effect cultures response, EMT profile features head neck cancer.Cancer Int. 19: 1-10Crossref (58) Moreover, do not conserve original shape polarization (Table By contrast, usually expensive, complex, difficult work with, associated ethical problems. also challenging analyze effects often representative human-specific events, limits applicability these [3.Asghar Scholar,17.Sung K.E. Beebe D.J. Microfluidic cancer.Adv. Deliv. 2014; 79: 68-78Crossref (107) multicellular overcome limitations experimental tractability relevance. reproduce mechanical cues development, morphology, cell–cell/cell–ECM stiffness, specific gradients [4.Langhans Scholar,14.Duval Scholar,18.Jensen Teng Y. Is time start transitioning culture?.Front. Biosci. 2020; 33Crossref (80) However, only one component cells. Thus, although new being developed, yet achieved. recent advances potential (i) discovery, (ii) be testing, (iii) enable development personalized treatments Scholar].Table 12D versus Culture MethodsCharacteristics2D3DRefsCell morphologyAltered shape, elongated; epithelial polarityThe natural preserved; aggregates[15.Mabry Scholar]Gene expressionCell adhesion-, proliferation-, survival-related modifiedAccurate representation gene patterns[16.Melissaridou Scholar,85.Riedl A. al.Comparison vs reveals differences AKT–mTOR–S6K responses.J. Sci. 130: 203-218Crossref (184) Scholar,86.Luca A.C. al.Impact phenotype, expression, EGFR inhibition colorectal lines.PLoS One. 8e59689Crossref (185) Scholar]Cell proliferation differentiationCell differentiation occurs at unnaturally rapid paceCells differentiated; realistic interactions[15.Mabry interactionsDeprived cell–cell cell–ECM no niches createdCell junctions common communication[14.Duval Scholar]Tumoral heterogeneityBasic; all receive same amount nutrients; inaccurate replication TMEBetter approximation TME; nutrients equally supplied[4.Langhans Scholar,51.Costa E.C. al.3D spheroids: techniques analysis.Biotechnol. Adv. 34: 1427-1441Crossref (216) Scholar]Response stimuliInaccurate cuesCells environment directions properly represent vivo stimuli[16.Melissaridou Scholar]ReproducibilityHighly replicableDifficult replicate conditions[4.Langhans Scholar]Analysis quantificationEasy interpretation results; long-term culturesDifficult data, when spheroid/organoid conformation[4.Langhans Scholar]CostCheaper large-scale studiesMore expensive techniques[18.Jensen Scholar] Open table tab This review presents within cell/ECM-based assays, cell-based microfluidics. each platform discussed, followed critical analysis novel should address establish clinically components almost control behavior external stimuli. Dynamic adhesion, cytoskeletal organization, Scholar,19.Bonnans al.Remodelling disease.Nat. Biol. 786-801Crossref (1636) For example, stiffness (desmoplasia), alongside establishment blood vessel network, contributes hypoxia epithelial-derived [19.Bonnans Scholar,20.Emon B. al.Biophysics metastasis mini review.Comput. Struct. Biotechnol. 16: 279-287Crossref (83) Furthermore, secretion hypoxia-inducible (HIFs) induces macrophage fibroblast recruitment hypoxic regions primary tumor, increased remodeling angiogenesis [21.Gilkes D.M. al.Hypoxia matrix: drivers metastasis.Nat. 14: 430-439Crossref (657) formation abnormal stimulates progression starts activation CAFs, contribute fibrosis alignment building up collagen fibers (mediated primarily LOX enzymes) [22.Hamidi Ivaska Every step way: integrins 533-548Crossref (354) addition, deregulated supports transformation hyperplasia Matrix metalloproteinases (MMPs) degradation metastatic sites Scholar,22.Hamidi every carcinogenesis function receptors mechanotransduction, instance, correlated overexpression β1 focal adhesion kinase RhoA/Rho-associated protein integrin-mediated fibronectin CAFs directional migration [23.Erdogan al.Cancer-associated aligning fibronectin.J. 216: 3799-3816Crossref (179) architecture over demonstrate spatiotemporal dynamics targets promising effective therapies. Given both tumor-inducing assays developed manipulate physiologically setting. An ideal scaffold appropriate proliferation/differentiation, generation closely context, cultured biomaterials, decellularized tissues, scaffolds based ceramics synthetic and/or polymers. Hydrogel-based typically preferred owing possibility tailoring properties 2). Scaffolds produced polymeric biomaterials polyethylene glycol (PEG), polycaprolactone (PCL), poly(hydroxyethylmethacrylate) (PHEMA), poly(lactic-co-glycolic acid) (PLGA), (such hydroxyapatite bioglass) [24.Feng al.Expansion breast fibrous scaffolds.Integr. 5: 768-777Crossref (50) Scholar,25.Long T.J. al.Prostate xenografts engineered precision-porous poly(2-hydroxyethyl methacrylate) hydrogels tumorigenesis dormancy escape.Biomaterials. 35: 8164-8174Crossref (20) Synthetic polymers ability modulate them required. modified peptides, RGD (Arg-Gly-Asp) peptides fibrinogen, adsorption [5.Rodenhizer hybrid combine soft [26.Rijal G. Li research.Biomaterials. 81: 135-156Crossref (99) PEG heparin were culturing prostate functionalized peptide motifs RGD, GFOGER (collagen I), IKVAV (laminin-111) [27.Taubenberger A.V. growth, invasion microenvironments.Acta Biomater. 36: 73-85Crossref (75) choice physical/chemical conditions determine will react substrate play outcome 2A,B). Natural collagen, fibrin, alginate, chitosan sourced tissues [28.Grolman J.M. al.Rapid extrusion microenvironments.Adv. 27: 5512-5517Crossref (69) 29.Rebelo S.P. al.3D-3-culture: tool unveil plasticity microenvironment.Biomaterials. 163: 185-197Crossref (66) 30.Hume R.D. al.Tumour invasiveness response chemotherapeutics adipocyte invested anisotropic scaffolds.Sci. Rep. 8: 12658Crossref (5) Alternatively, (dECM) offers advantage recreating environments without compromising tissue-specific ECM, thereby generating structural similar those [31.Ferreira L.P. al.Decellularized bioengineering physiomimetic models.Trends 38: 1397-1414Abstract Full Text PDF (14) Scholar,32.Lü W.D. al.Development acellular three-dimensional engineering.PLoS 9e103672Crossref (54) Most commonly substitutes, Matrigel, undefined highly variable affect results reproducibility model [33.Drost Organoids research.Nat. 407-418Crossref (400) close resemblance structure, easily replicated dECM-based after cellularization. dECMs alternatives vitro, individual whole [34.Gill B.J. West J.L. Modeling engineering repurposed frontiers biology.J. Biomech. 47: 1969-1978Crossref (59) decellularization process, however, its ensure intactness detergents enzymes. With considerations mind, modifications scaffold-based optimized modeling. (TMS) using methods biophysical/biochemical [35.Rijal versatile system screening.Sci. 3e1700764Crossref (53) consists multilayered prepared mammary tissue. compartmental fashion intracellular biomarkers confirming correct proliferation. TMS mimics structure while providing simple-to-use screening approach, was seeded adipocytes [30.Hume allowed examination pores aligned perpendicular surface, reflecting organizes spatial configuration. into compared two lines overexpressing Wnt1 Her2. presence types, promoted reducing overall number migratory demonstrating heterogeneity proper ECM-mimicking offer inexpensive analyzable tunable instructive One study showed significant difference levels affecting remodeling, namely processes resulted radio- chemoresistance Matrigel culture, highlights reproduction findings [36.Zschenker O. al.Genome-wide but DNA repair.PLoS 2012; 7e34279Crossref (93) applied produce bioprinted induce assembly spheroids, microfluidic platforms, explained detail next sections. use fabrication paved way bioprinting create well-defined architecture, composition, high 2C) [37.Langer E.M. phenotypes bioprinting.Cell 26: 608-623Abstract printing emerging approach patterning facilitates temporal distribution Common extrusion-, inkjet-, stereolithography-based laser-assisted electrospinning-based (Box 1) [38.Heinrich M.A. bioprinting: benches translational applications.Small. 15e1805510Crossref process must avoid damaging pressure/heat sensitive fluids, living Therefore, biomaterial consider biocompatibility, shape-fidelity material, level instructiveness required.Box 1Microfabrication Techniques Produce Constructs DevicesOver past decades, improved design cell-laden constructs. Each technologies application-specific depends type bioink [40.Moroni L. al.Biofabrication stra

Language: Английский

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A human breast cancer-derived xenograft and organoid platform for drug discovery and precision oncology

Nature Cancer, Journal Year: 2022, Volume and Issue: 3(2), P. 232 - 250

Published: Feb. 24, 2022

Models that recapitulate the complexity of human tumors are urgently needed to develop more effective cancer therapies. We report a bank patient-derived xenografts (PDXs) and matched organoid cultures from represent greatest unmet need: endocrine-resistant, treatment-refractory metastatic breast cancers. leverage PDXs PDX-derived organoids (PDxO) for drug screening is feasible cost-effective with in vivo validation. Moreover, we demonstrate feasibility using these models precision oncology real time clinical care case triple-negative (TNBC) early recurrence. Our results uncovered Food Drug Administration (FDA)-approved high efficacy against models. Treatment this therapy resulted complete response individual progression-free survival (PFS) period than three times longer their previous This work provides valuable methods resources functional medicine development cancer.

Language: Английский

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Patient-Derived Ovarian Cancer Organoids Mimic Clinical Response and Exhibit Heterogeneous Inter- and Intrapatient Drug Responses

Cell Reports, Journal Year: 2020, Volume and Issue: 31(11), P. 107762 - 107762

Published: June 1, 2020

There remains an unmet need for preclinical models to enable personalized therapy ovarian cancer (OC) patients. Here we evaluate the capacity of patient-derived organoids (PDOs) predict clinical drug response and functional consequences tumor heterogeneity. We included 36 whole-genome-characterized PDOs from 23 OC patients with known histories. maintain genomic features original lesion recapitulate patient neoadjuvant carboplatin/paclitaxel combination treatment. display inter- intrapatient heterogeneity chemotherapy targeted drugs, which can be partially explained by genetic aberrations. PDO screening identifies high responsiveness at least one 88% are valuable that provide insights into individual OC, complementary testing. Generating multiple locations improve decision making increase our knowledge

Language: Английский

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Application of Highly Immunocompromised Mice for the Establishment of Patient-Derived Xenograft (PDX) Models

Cells, Journal Year: 2019, Volume and Issue: 8(8), P. 889 - 889

Published: Aug. 13, 2019

Patient-derived xenograft (PDX) models are created by engraftment of patient tumor tissues into immunocompetent mice. Since a PDX model retains the characteristics primary including gene expression profiles and drug responses, it has become most reliable in vivo human cancer model. The rate increases with introduction Non-obese diabetic Severe combined immunodeficiency (NOD/SCID)-based immunocompromised mice, especially NK-deficient NOD strains NOD/SCID/interleukin-2 receptor gamma chain(IL2Rγ)null (NOG/NSG) NOD/SCID/Jak3(Janus kinase 3)null (NOJ). Success rates differ origin: gastrointestinal tumors acquire higher rate, while is lower for breast cancers. Subcutaneous transplantation popular method to establish PDX, but some require specific environments, e.g., orthotropic or renal capsule transplantation. Human hormone treatment necessary hormone-dependent cancers such as prostate mice hematopoietic immune systems (humanized PDX) powerful tools analysis tumor–immune system interaction evaluation immunotherapy response. A biobank equipped patients’ clinical data, gene-expression patterns, mutational statuses, tissue architects, responsiveness will be an authoritative resource developing biomarkers chemotherapeutic predictions, creating individualized therapy, establishing precise medicine.

Language: Английский

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Patient-derived xenograft models in cancer therapy: technologies and applications

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: April 12, 2023

Abstract Patient-derived xenograft (PDX) models, in which tumor tissues from patients are implanted into immunocompromised or humanized mice, have shown superiority recapitulating the characteristics of cancer, such as spatial structure cancer and intratumor heterogeneity cancer. Moreover, PDX models retain genomic features across different stages, subtypes, diversified treatment backgrounds. Optimized engraftment procedures modern technologies multi-omics deep learning enabled a more comprehensive depiction molecular landscape boosted utilization models. These irreplaceable advantages make an ideal choice studies, preclinical trials novel drugs, validating drug combinations, screening drug-sensitive patients, exploring resistance mechanisms. In this review, we gave overview history process model establishment. Subsequently, review presents strengths weaknesses highlights integration research. Finally, delineated broad application chemotherapy, targeted therapy, immunotherapy, other therapies.

Language: Английский

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Modeling neoplastic disease with spheroids and organoids

Journal of Hematology & Oncology, Journal Year: 2020, Volume and Issue: 13(1)

Published: July 16, 2020

Abstract Cancer is a complex disease in which both genetic defects and microenvironmental components contribute to the development, progression, metastasization of disease, representing major hurdles identification more effective safer treatment regimens for patients. Three-dimensional (3D) models are changing paradigm preclinical cancer research as they closely resemble tissue environment architecture found clinical tumors than bidimensional (2D) cell cultures. Among 3D models, spheroids organoids represent most versatile promising that capable recapitulating heterogeneity pathophysiology human cancers filling gap between conventional 2D vitro testing animal models. Such systems powerful tool studying biology, enabling us model dynamic evolution neoplastic from early stages metastatic dissemination interactions with microenvironment. Spheroids have recently been used field drug discovery personalized medicine. The combined use could potentially improve robustness reliability data, reducing need favoring their transition practice. In this review, we summarize recent advances these modeling, focusing on innovative translational applications, looking at future challenges, comparing them widely

Language: Английский

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Smart Nanomaterials in Cancer Theranostics: Challenges and Opportunities

ACS Omega, Journal Year: 2023, Volume and Issue: 8(16), P. 14290 - 14320

Published: April 10, 2023

Cancer is ranked as the second leading cause of death globally. Traditional cancer therapies including chemotherapy are flawed, with off-target and on-target toxicities on normal cells, requiring newer strategies to improve cell selective targeting. The application nanomaterial has been extensively studied explored chemical biology tools in theranostics. It shows greater applications toward stability, biocompatibility, increased permeability, resulting precise targeting, mitigating shortcomings traditional therapies. nanoplatform offers an exciting opportunity gain targeting multifunctionality. advent nanotechnology, particular development smart nanomaterials, transformed diagnosis treatment. large surface area nanoparticles enough encapsulate many molecules ability functionalize various biosubstrates such DNA, RNA, aptamers, antibodies, which helps theranostic action. Comparatively, biologically derived nanomaterials perceive advantages over produced by conventional methods terms economy, ease production, reduced toxicity. present review summarizes techniques theranostics emphasizes (such organic (NPs), inorganic NPs, carbon-based NPs). We also critically discussed challenges impeding their translation treatment diagnostic applications. This concludes that use could significantly will facilitate new dimensions for tumor detection therapy.

Language: Английский

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Breast Cancer: A Molecularly Heterogenous Disease Needing Subtype-Specific Treatments

Medical Sciences, Journal Year: 2020, Volume and Issue: 8(1), P. 18 - 18

Published: March 23, 2020

Breast cancer is the most commonly occurring in women. There were over two-million new cases world 2018. It second leading cause of death from western countries. At molecular level, breast a heterogeneous disease, which characterized by high genomic instability evidenced somatic gene mutations, copy number alterations, and chromosome structural rearrangements. The caused defects DNA damage repair, transcription, replication, telomere maintenance mitotic segregation. According to features, cancers are subdivided subtypes, according activation hormone receptors (estrogen receptor progesterone receptor), human epidermal growth factors 2 (HER2), or BRCA mutations. In-depth analyses features primary metastatic have shown great heterogeneity genetic alterations their clonal evolution during disease development. These studies contributed identify repertoire numerous disease-causing genes that altered through different mutational processes. While early-stage curable about 70% patients, advanced largely incurable. However, develop therapeutic approaches targeting HER2, CDK4/6, PI3K, involving poly(ADP-ribose) polymerase inhibitors for mutation carriers immunotherapy.

Language: Английский

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