RESUMO
Nanomedicines for treating chronic kidney disease (CKD) are on the horizon, yet their delivery to renal tubules where tubulointerstitial fibrosis occurs remains inefficient. We report a folic acid-conjugated gold nanoparticle that can transport into renal tubules and treat tubulointerstitial fibrosis in mice with unilateral ureteral obstruction. The 3-nm gold core allows for the dissection of bio-nano interactions in the fibrotic kidney, ensures the overall nanoparticle (~7 nm) to be small enough for glomerular filtration, and naturally inhibits the p38α mitogen-activated protein kinase in the absence of chemical or biological drugs. The folic acids support binding to selected tubule cells with overexpression of folate receptors and promote retention in the fibrotic kidney. Upon intravenous injection, this nanoparticle can selectively accumulate in the fibrotic kidney over the nonfibrotic contralateral kidney at ~3.6% of the injected dose. Delivery to the fibrotic kidney depends on nanoparticle size and disease stage. Notably, a single injection of this self-therapeutic nanoparticle reduces tissue degeneration, inhibits genes related to the extracellular matrix, and treats fibrosis more effectively than standard Captopril therapy. Our data underscore the importance of constructing CKD nanomedicines based on renal pathophysiology.
Assuntos
Nanopartículas Metálicas , Insuficiência Renal Crônica , Camundongos , Animais , Ouro/farmacologia , Ácido Fólico/metabolismo , Nanopartículas Metálicas/uso terapêutico , Rim/metabolismo , Insuficiência Renal Crônica/metabolismo , FibroseRESUMO
Atherosclerosis treatments by gene regulation are garnering attention, yet delivery of gene cargoes to atherosclerotic plaques remains inefficient. Here, we demonstrate that assembly of therapeutic oligonucleotides into a three-dimensional spherical nucleic acid nanostructure improves their systemic delivery to the plaque and the treatment of atherosclerosis. This noncationic nanoparticle contains a shell of microRNA-146a oligonucleotides, which regulate the NF-κB pathway, for achieving transfection-free cellular entry. Upon an intravenous injection into apolipoprotein E knockout mice fed with a high-cholesterol diet, this nanoparticle naturally targets class A scavenger receptor on plaque macrophages and endothelial cells, contributing to elevated delivery to the plaques (â¼1.2% of the injected dose). Repeated injections of the nanoparticle modulate genes related to immune response and vascular inflammation, leading to reduced and stabilized plaques but without inducing severe toxicity. Our nanoparticle offers a safe and effective treatment of atherosclerosis and reveals the promise of nucleic acid nanotechnology for cardiovascular disease.
Assuntos
Aterosclerose , MicroRNAs , Nanopartículas , Placa Aterosclerótica , Animais , Aterosclerose/tratamento farmacológico , Aterosclerose/genética , Células Endoteliais/metabolismo , Camundongos , Camundongos Knockout , MicroRNAs/genética , MicroRNAs/uso terapêutico , NF-kappa B/genética , NF-kappa B/metabolismo , Nanopartículas/química , Nanopartículas/uso terapêutico , Oligonucleotídeos/uso terapêutico , Placa Aterosclerótica/metabolismo , Receptores Depuradores/metabolismoRESUMO
The local microenvironment where tumors develop can shape cancer progression and therapeutic outcome. Emerging evidence demonstrate that the efficacy of immune-checkpoint blockade (ICB) is undermined by fibrotic tumor microenvironment (TME). The majority of hepatocellular carcinoma (HCC) develops in liver fibrosis, in which the stromal and immune components may form a barricade against immunotherapy. Here, we report that nanodelivery of a programmed death-ligand 1 (PD-L1) trap gene exerts superior efficacy in treating fibrosis-associated HCC when compared with the conventional monoclonal antibody (mAb). In two fibrosis-associated HCC models induced by carbon tetrachloride and a high-fat, high-carbohydrate diet, the PD-L1 trap induced significantly larger tumor regression than mAb with no evidence of toxicity. Mechanistic studies revealed that PD-L1 trap, but not mAb, consistently reduced the M2 macrophage proportion in the fibrotic liver microenvironment and promoted cytotoxic interferon gamma (IFNγ)+tumor necrosis factor α (TNF-α)+CD8+T cell infiltration to the tumor. Moreover, PD-L1 trap treatment was associated with decreased tumor-infiltrating polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC) accumulation, resulting in an inflamed TME with a high cytotoxic CD8+T cell/PMN-MDSC ratio conductive to anti-tumor immune response. Single-cell RNA sequencing analysis of two clinical cohorts demonstrated preferential PD-L1 expression in M2 macrophages in the fibrotic liver, thus supporting the translational potential of nano-PD-L1 trap for fibrotic HCC treatment.
Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/tratamento farmacológico , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Antineoplásicos/uso terapêutico , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Cirrose Hepática/etiologia , Cirrose Hepática/tratamento farmacológico , Microambiente TumoralRESUMO
DNA nanostructures are attractive gene carriers for nanomedicine applications, yet their delivery to the nucleus remains inefficient. We present the application of extracellular mechanical stimuli to activate cellular mechanotransduction for boosting the intranuclear delivery of DNA nanostructures. Treating mammalian cells with polythymidine-rich spherical nucleic acids (poly(T) SNAs) under gentle compression by a single coverslip leads to up to â¼50% nuclear accumulation without severe endosomal entrapment, cytotoxicity, or long-term membrane damage; no chemical modification or transfection reagent is needed. Gentle compression activates Rho-ROCK mechanotransduction and causes nuclear translocation of YAP. Joint compression and treatment with poly(T) oligonucleotides upregulate genes linked to myosin, actin filament, and nuclear import. In turn, Rho-ROCK, myosin, and importin mediate the nuclear entry of poly(T) SNAs. Treatment of endothelioma cells with poly(T) SNAs bearing antisense oligonucleotides under compression inhibits an intranuclear oncogene. Our data should inspire the marriage of DNA nanotechnology and cellular biomechanics for intranuclear applications.
Assuntos
Nanoestruturas , Ácidos Nucleicos , Animais , DNA/genética , Mamíferos , Mecanotransdução Celular , Nanomedicina , Ácidos Nucleicos/químicaRESUMO
Our knowledge in how extracellular vesicles (EVs) are secreted from cells remains inadequate due to the limited technologies available for visualizing them in situ. We report a pH-reversible boron dipyrromethene (BODIPY) fluorescent probe for confocal imaging of EVs secreted from living cells without inducing severe cytotoxicity. This probe predominantly assumes a non-fluorescent leuco-BODIPY form under basic conditions, but it gradually switches to its fluorescent parent BODIPY form upon acidification; such pH transition empowers the imaging of acidic EVs (such as CD81-enriched exosomes and extracellular multivesicular bodies) in weakly basic culture medium and intracellular acidic precursor EVs in weakly basic cytoplasm, with minimal false positive signals frequently encountered for "always-on" dyes. Joint application of this probe with plasmid transfection reveals the secretion of some EVs from cellular pseudopodia via microtubule trackways. This probe may provide mechanistic insights into the extracellular transport of EVs and support the development of EV-based nanomedicines.
Assuntos
Exossomos , Vesículas Extracelulares , Corantes Fluorescentes , Células HEK293 , Humanos , Concentração de Íons de HidrogênioRESUMO
Nanosubstrate engineering is an established approach for modulating cellular responses, but it remains infrequently exploited to facilitate the intracellular delivery of nanoparticles (NPs). We report nanoscale roughness of the extracellular environment as a critical parameter for regulating the cellular uptake of NPs. After seeding cells atop a substrate that contains randomly immobilized gold NPs (termed AuNP-S) with sub-10 nm surface roughness, we demonstrate that such cells internalize up to â¼100-fold more poly(ethylene glycol)-coated AuNPs (Au@PEG NPs) than those cells seeded on a conventional flat culture plate. Our result is generalizable to 4 different cell types and Au@PEG NPs modified with 13 different hydrocarbyl functional groups. Conditioning cells to AuNP-S not only leads to upregulation of clathrin- and integrin-related genes, but also supports elevated uptake of Au@PEG NPs via clathrin-mediated endocytosis. Our data suggest a simple and robust method for boosting the intracellular delivery of nanomedicines by nanosubstrate engineering.
Assuntos
Nanopartículas Metálicas , Nanopartículas , Clatrina , Endocitose , Ouro , PolietilenoglicóisRESUMO
We present a self-therapeutic nanoparticle for topical delivery to epidermal keratinocytes to prevent and treat psoriasis. Devoid of known chemical or biological antipsoriatic drugs, this sub-15 nm nanoparticle contains a 3 nm gold core and a shell of 1000 Da polyethylene glycol strands modified with 30% octadecyl chains. When it is applied to imiquimod-induced psoriasis mice without an excipient, the nanoparticle can cross the stratum corneum and preferentially enter keratinocytes. Applying the nanoparticles concurrently with imiquimod prevents psoriasis and downregulates genes that are enriched in the downstream of the interleukin-17 signaling pathway and linked to epidermis hyperproliferation and inflammation. Applying the nanoparticles after psoriasis is established treats the psoriatic skin as effectively as standard steroid and vitamin D analog-based therapy but without hair loss and skin wrinkling. The nanoparticles do not accumulate in major organs or induce long-term toxicity. Our nanoparticle offers a simple, safe, and effective alternative for treating psoriasis.
Assuntos
Nanopartículas Metálicas , Nanopartículas , Psoríase , Animais , Modelos Animais de Doenças , Ouro , Imiquimode , Queratinócitos , Camundongos , Psoríase/tratamento farmacológicoRESUMO
Designing nanoparticles (NPs) with desirable cell type-specific exocytosis properties, say promoting their exocytosis from scavenging cell types (e.g., macrophages and endothelial cells) or suppressing their exocytosis from target disease cell types (e.g., cancer cells), improves the application of nanomedicines. However, the design parameters available for tuning the exocytosis of NPs remain scarce in the "nano-cell" literature. Here, we demonstrate that surface modification of NPs with hydrocarbyl functional groups, commonly found in biomolecules and NP-based drug carriers, is a critical parameter for tuning the exocytosis of NPs from RAW264.7 macrophages, C166 endothelial cells, and HeLa epithelial cancer cells. To exclude the effect of hydrophobicity, we prepare a collection of hydrophilic NPs that bear a gold NP (AuNP) core, a dense polyethylene glycol (PEG) shell, and different types of hydrocarbyl groups (X) that are attached to the distal end of the PEG strands (termed "Au@PEG-X NPs"). For all three cell types tested, modification of NPs with straight-chain dodecane leads to a >10-fold increase in the level of cellular uptake, drastically higher than those of all other types of X tested. However, the probability of exocytosis of NPs significantly depends on the types of cell and X. Notably, NPs modified with cyclododecanes are most likely to be exocytosed by RAW264.7 and C166 cells (but not HeLa cells), accompanied by the release of intralumenal vesicles to the extracellular milieu. These data suggest a reductionist approach for rationally assembling bionanomaterials for nanomedicine applications by using hydrocarbyl functional groups as building blocks.
Assuntos
Exocitose , Nanopartículas/química , Animais , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Células Endoteliais/metabolismo , Ouro/química , Células HeLa , Humanos , Nanopartículas Metálicas/química , Camundongos , Tamanho da Partícula , Polietilenoglicóis/química , Células RAW 264.7 , Propriedades de SuperfícieRESUMO
Polyglutamine (polyQ) diseases, such as Huntington's disease and several types of spinocerebellar ataxias, are dominantly inherited progressive neurodegenerative disorders and characterized by the presence of expanded CAG trinucleotide repeats in the respective disease locus of the patient genomes. Patients with polyQ diseases currently need to rely on symptom-relieving treatments because disease-modifying therapeutic interventions remain scarce. Many disease-modifying therapeutic agents are now under clinical testing for treating polyQ diseases, but their delivery to the brain is often too invasive (e.g., intracranial injection) or inefficient, owing to in vivo degradation and clearance by physiological barriers (e.g., oral and intravenous administration). Nanoparticles provide a feasible solution for improving drug delivery to the brain, as evidenced by an increasing number of preclinical studies that document the efficacy of nanomedicines for polyQ diseases over the past 5-6 years. In this review, we present the pathogenic mechanisms of polyQ diseases, the common animal models of polyQ diseases for evaluating the efficacy of nanomedicines, and the common administration routes for delivering nanoparticles to the brain. Next, we summarize the recent preclinical applications of nanomedicines for treating polyQ diseases and improving neurological conditions in vivo, placing emphasis on antisense oligonucleotides, small peptide inhibitors, and small molecules as the disease-modifying agents. We conclude with our perspectives of the burgeoning field of "nanomedicines for polyQ diseases", including the use of inorganic nanoparticles and potential drugs as next-generation nanomedicines, development of higher-order animal models of polyQ diseases, and importance of "brain-nano" interactions.
Assuntos
Portadores de Fármacos/química , Doença de Huntington/tratamento farmacológico , Nanopartículas/química , Fármacos Neuroprotetores/administração & dosagem , Peptídeos/antagonistas & inibidores , Ataxias Espinocerebelares/tratamento farmacológico , Administração Intranasal , Administração Oral , Animais , Animais Geneticamente Modificados , Disponibilidade Biológica , Barreira Hematoencefálica/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Loci Gênicos/genética , Humanos , Doença de Huntington/genética , Doença de Huntington/patologia , Injeções Intraperitoneais , Injeções Intravenosas , Injeções Intraventriculares , Injeções Espinhais , Fármacos Neuroprotetores/farmacocinética , Oligonucleotídeos Antissenso/administração & dosagem , Oligonucleotídeos Antissenso/farmacocinética , Peptídeos/genética , Peptídeos/metabolismo , Permeabilidade , Medula Espinal/efeitos dos fármacos , Medula Espinal/patologia , Ataxias Espinocerebelares/genética , Ataxias Espinocerebelares/patologia , Distribuição Tecidual , Expansão das Repetições de TrinucleotídeosRESUMO
Advances in nanotechnology have empowered the design of bionanomaterials by assembling different types of natural biomolecules (e.g., nucleic acids, proteins, and lipids) as building blocks into nanoparticles (NPs) of 1-100 nm in diameter. Such bionanomaterials form the basis of useful nanomedicine applications, such as targeted delivery, gene regulation, molecular diagnostics, and immunomodulation. To achieve optimal performance in these applications, it is imperative that the NPs be delivered effectively to the organs, tissues, and cells of interest. A rational approach to facilitating the delivery of NPs is to develop a detailed and comprehensive understanding in their fundamental interactions with the biological system (or nano-bio interactions). Rigorous nano-bio research can provide mechanistic insights for circumventing the bottlenecks associated with inefficient and nonspecific delivery of NPs, catalyzing the clinical translation of nanomedicines. Cationic liposomes and lipid NPs are conventional carriers of therapeutic cargoes into cells due to their high ability to penetrate the cell membrane, a barrier comprised by an anionic phospholipid bilayer. Yet, cationic NPs tend to cause cytotoxicity and immune responses that may hamper their clinical translation. Contrary to cationic NPs, non-cationic NPs (be they near-neutral or anionic in surface charge) generally exhibit higher biocompatibility but enter mammalian cells in much less pronounced amounts. Intriguingly, some types of non-cationic NPs exhibit high biocompatibility and cellular uptake properties, all attractive features for intracellular delivery. In this Account, we present our studies of the interactions of non-cationic bionanomaterials with cells (or nano-cell interactions). To start with, we introduce the use of near-neutral poly(ethylene glycol)-coated NPs for probing the roles of two rarely explored physicochemical parameters on cellular uptake, namely, extracellular compression and alkylation. We next present the nano-cell interactions of two representative types of anionic bionanomaterials that effectively enter mammalian cells and have found widespread applications in the past decade, including DNA-coated NPs and polydopamine (PDA)-coated NPs. In our cell-based studies, we dissect the route of intracellular trafficking, pathway proteins that dictate cellular uptake, and trafficking of NPs. We further touch on our recent quantitative analysis of the cellular-level distribution of NPs in various organs and tissues of diseased animal models. Our results offer important design rules of NPs for achieving effective intracellular delivery and may even guide us to explore nanomedicine applications that we did not conceive before, such as using DNA-coated NPs for targeting atherosclerotic plaques and PDA-coated plasmonic nanoworms for photothermal killing of cancer cells. We conclude with our perspectives in elucidating nano-bio interactions via a reductionist approach, calling for closer attention to the role of functional groups and more refined studies on the organelle-level distribution of NPs and the genetic basis of in vivo distribution of NPs.
Assuntos
Transporte Biológico/fisiologia , Nanopartículas/metabolismo , Animais , Linhagem Celular Tumoral , DNA/química , Endocitose/fisiologia , Feminino , Ouro/química , Humanos , Indóis/química , Masculino , Camundongos , Polietilenoglicóis/química , Polímeros/químicaRESUMO
Advances in DNA nanotechnology empower the programmable assembly of DNA building blocks (oligonucleotides and plasmids) into DNA nanostructures with precise architectural control. As DNA nanostructures are biocompatible and can naturally enter mammalian cells without the aid of transfection agents, they have found numerous biological or biomedical applications as delivery carriers of therapeutic and imaging cargoes into mammalian cells for at least a decade. Nevertheless, mechanistic studies on how DNA nanostructures interact with cells have remained limited and incomprehensive until 2-3 years ago. This Review presents the recent progress in elucidating the "cell-nano" interactions of DNA nanostructures, with an emphasis on three key classes of structures commonly utilized in intracellular applications: tile-based structures, origami-based structures, and nanoparticle-templated structures. Structural parameters of DNA nanostructures and strategies of biochemical modification for promoting intracellular delivery are discussed. Biological mechanisms for cellular uptake, including specific pathways and receptors involved, are outlined. Routes of intracellular trafficking and degradation, together with strategies for re-directing their trafficking, are delineated. This Review concludes with several aspects of the "bio-nano" interactions of DNA nanostructures that warrant future investigations.
Assuntos
DNA/química , Nanoestruturas/química , Animais , Humanos , Nanomedicina/métodos , Nanotecnologia/métodosRESUMO
Motivation: Toehold switches are a class of RNAs with a hairpin loop that can be unfolded upon binding a trigger RNA, thereby exposing a ribosome binding site (RBS) and permitting translation of the reporter protein. They have been shown very useful in detecting a variety of targets including RNAs from Zika and Ebola viruses. The base complementation between the toehold switch and the trigger RNA also makes it sensitive to sequence variations. Design of toehold switches involves a series of considerations related to their sequence properties, structures and specificities. Results: Here we present the first comprehensive web tool for designing toehold switches. We also propose a score for predicting the efficacy of designed toehold switches based on properties learned from â¼180 experimentally tested switches. Availability and implementation: The toehold switch web tool is available at https://yiplab.cse.cuhk.edu.hk/toehold/.
Assuntos
Design de Software , Sítios de Ligação , Conformação de Ácido Nucleico , RNA/química , Ribossomos/metabolismoRESUMO
Atherosclerosis, driven by chronic inflammation of the arteries and lipid accumulation on the blood vessel wall, underpins many cardiovascular diseases with high mortality rates globally, such as stroke and ischemic heart disease. Engineered bio-nanomaterials are now under active investigation as carriers of therapeutic and/or imaging agents to atherosclerotic plaques. This Review summarizes the latest bio-nanomaterial-based strategies for managing atherosclerosis published over the past five years, a period marked by a rapid surge in preclinical applications of bio-nanomaterials for imaging and/or treating atherosclerosis. To start, the biomarkers exploited by emerging bio-nanomaterials for targeting various components of atherosclerotic plaques are outlined. In addition, recent efforts to rationally design and screen for bio-nanomaterials with the optimal physicochemical properties for targeting plaques are presented. Moreover, the latest preclinical applications of bio-nanomaterials as carriers of imaging, therapeutic, or theranostic agents to atherosclerotic plaques are discussed. Finally, a mechanistic understanding of the interactions between bio-nanomaterials and the plaque ("athero-nano" interactions) is suggested, the opportunities and challenges in the clinical translation of bio-nanomaterials for managing atherosclerosis are discussed, and recent clinical trials for atherosclerotic nanomedicines are introduced.
Assuntos
Aterosclerose/diagnóstico por imagem , Nanomedicina/métodos , Animais , Aterosclerose/tratamento farmacológico , Humanos , Nanopartículas/química , Nanoestruturas/químicaRESUMO
Polydopamine (PDA)-coated nanoparticles are adhesive bionanomaterials widely utilized in intracellular applications, yet how their adhesiveness affects their colloidal stability and their interactions with serum proteins and mammalian cells remain unclear. In this work, we systematically investigate the combined effects of dopamine (DA) concentration and polymerization time (both reaction parameters spanning 2 orders of magnitude) on the morphological diversity of PDA-coated nanoparticles by coating PDA onto gold nanoparticle cores. Independent of the DA concentration, Au@PDA NPs remain largely aggregated upon several hours of limited polymerization; interestingly, extended polymerization for 2 days or longer yield randomly aggregated NPs, nearly monodisperse NPs, or worm-like NP chains in the ascending order of DA concentration. Upon exposure to serum proteins, the specific type of proteins adsorbed to the Au@PDA NPs strongly depends upon the DA concentration. As DA concentration increases, less albumin and more hemoglobin subunits adhere. Moreover, cellular uptake is a strong function of polymerization time. Serum-stabilized Au@PDA NPs prepared by limited polymerization enter Neuro-2a and HeLa cancer cells more abundantly than those prepared by extended polymerization. Our data underscore the importance of DA concentration and polymerization time for tuning the morphology and degree of intracellular delivery of PDA-coated nanostructures.
Assuntos
Ouro/química , Indóis/química , Nanopartículas Metálicas/química , Polímeros/química , Coroa de Proteína/química , Adsorção , Transporte Biológico , Dopamina/química , Células HeLa , Humanos , Indóis/metabolismo , Polímeros/metabolismoRESUMO
Functional siRNAs are employed as cross-linkers to direct the self-assembly of DNA-grafted polycaprolactone (DNA-g-PCL) brushes to form spherical and nanosized hydrogels via nucleic acid hybridization in which small interfering RNAs (siRNAs) are fully embedded and protected for systemic delivery. Owing to the existence of multivalent mutual crosslinking events inside, the crosslinked nanogels with tunable size exhibit not only good thermostability, but also remarkable physiological stability that can resist the enzymatic degradation. As a novel siRNA delivery system with spherical nucleic acid (SNA) architecture, the crosslinked nanogels can assist the delivery of siRNAs into different cells without any transfection agents and achieve the gene silencing effectively both inâ vitro and inâ vivo, through which a significant inhibition of tumor growth is realized in the anticancer treatment.
Assuntos
DNA/química , Sistemas de Liberação de Medicamentos , Neoplasias Experimentais/tratamento farmacológico , Polietilenoglicóis/química , Polietilenoimina/química , RNA Interferente Pequeno/administração & dosagem , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Células HeLa , Humanos , Camundongos , Nanogéis , Neoplasias Experimentais/patologia , Poliésteres/química , RNA Interferente Pequeno/química , RNA Interferente Pequeno/farmacologia , RNA Interferente Pequeno/uso terapêuticoRESUMO
Biomedical applications of non-spherical nanoparticles such as photothermal therapy and molecular imaging require their efficient intracellular delivery, yet reported details on their interactions with the cell remain inconsistent. Here, the effects of nanoparticle geometry and receptor targeting on the cellular uptake and intracellular trafficking are systematically explored by using C166 (mouse endothelial) cells and gold nanoparticles of four different aspect ratios (ARs) from 1 to 7. When coated with poly(ethylene glycol) strands, the cellular uptake of untargeted nanoparticles monotonically decreases with AR. Next, gold nanoparticles are functionalized with DNA oligonucleotides to target Class A scavenger receptors expressed by C166 cells. Intriguingly, cellular uptake is maximized at a particular AR: shorter nanorods (AR = 2) enter C166 cells more than nanospheres (AR = 1) and longer nanorods (AR = 4 or 7). Strikingly, long targeted nanorods align to the cell membrane in a near-parallel manner followed by rotating by ≈90° to enter the cell via a caveolae-mediated pathway. Upon cellular entry, targeted nanorods of all ARs predominantly traffic to the late endosome without progressing to the lysosome. The studies yield important materials design rules for drug delivery carriers based on targeted, anisotropic nanoparticles.
Assuntos
Endocitose , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Ouro/química , Nanotubos/química , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular , DNA/metabolismo , Endocitose/efeitos dos fármacos , Células Endoteliais/ultraestrutura , Camundongos , Modelos Biológicos , Nanotubos/toxicidade , Nanotubos/ultraestrutura , Polietilenoglicóis/químicaRESUMO
Recent breakthroughs and advances in nanoscience and nanotechnology have profoundly impacted young-generation education, accelerated knowledge transfer to enhance the quality of life, and improved environmental and economic sustainability. The Chinese University of Hong Kong (CUHK), a globally recognized education and research institute, has played a crucial role in promoting major strategic research directions in nanoscience, including translational biomedicine and information and automation technology, as well as environment and sustainability. To celebrate the 60th Anniversary of CUHK, we present this Virtual Issue that showcases the cutting-edge research at CUHK published in ACS Nano.
RESUMO
Polydopamine (PDA) nanoparticles (NPs) have diverse nanomedicine applications owing to their biocompatibility and abundant entry to cells. Yet, our knowledge in their interactions with cells was infrequently studied until recent years. This review presents the latest insights into the cell-nano interactions of PDA NPs, including their 'self-targeting' to dopamine receptors for cellular entry without the aid of ligands, in vitro 'self-therapeutic' cellular responses (antiferroptosis, macrophage polarization, and modulation of mitochondrial bioenergetics) in the absence of drugs, and in vivo cellular localization and pharmacological properties upon various routes of administration. This review concludes with our perspectives on the therapeutic promise of PDA NPs and the need for studies on PDA biochemistry, biodegradability, and protein adsorption.