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1.
Bioact Mater ; 9: 590-601, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34853819

RESUMO

CRISPR/Cas9-based gene editing has emerged as a powerful biotechnological tool, that relies on Cas9 protein and single guided RNA (sgRNA) to edit target DNA. However, the lack of safe and efficient delivery carrier is one of the crucial factors restricting its clinical transformation. Here, we report an ionizable lipid nanoparticle (iLP181, pKa = 6.43) based on iLY1809 lipid enabling robust gene editing in vitro and in vivo. The iLP181 effectively encapsulate psgPLK1, the best-performing plasmid expressing for both Cas9 protein and sgRNA targeting Polo-like kinase 1 (PLK1). The iLP181/psgPLK1 nanoformulation showed uniformity in size, regular nanostructure and nearly neutral zeta potential at pH 7.4. The nanoformulation effectively triggered editing of PLK1 gene with more than 30% efficiency in HepG2-Luc cells. iLP181/psgPLK1 significantly accumulated in the tumor for more than 5 days after a single intravenous injection. In addition, it also achieved excellent tumor growth suppression compared to other nucleic acid modalities such as siRNA, without inducing adverse effects to the main organs including the liver and kidneys. This study not only provides a clinically-applicable lipid nanocarrier for delivering CRISPR/Cas system (even other bioactive molecules), but also constitutes a potential cancer treatment regimen base on DNA editing of oncogenes.

2.
J Phys Chem Lett ; 12(46): 11280-11287, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34767373

RESUMO

Zeolitic imidazolate frameworks (ZIFs), widely regarded as promising materials for application in catalysis and separation, hold an increasingly significant position in drug delivery systems for their high drug loading capacity. Focused specifically on the rational design of targeting and bioresponsive nanovehicles, a neuropeptide Y1 receptor ligand (Y1L)-modified cell membrane camouflaged bioresponsive ZIF system (Y1L-RBC@ZIF-90@Ce6) was constructed for targeted photodynamic therapy of breast cancer. The biomimetic ZIF-based nanocarrier enhanced tumor accumulation by both neuropeptide Y1 receptor-targeted guidance and long-term stability. Y1L served as a good ligand-mediated selective targeting molecule for breast cancer, and red blood cell membrane-camouflaged nanocomposites displayed favorable biocompatibility. With the dual response of the ZIF to pH and adenosine triphosphate, the stimulus responsive photosensitizer Chlorin e6 delivery system effectively suppressed tumors in vivo. This work offers a platform for developing much safer and more efficient photodynamic therapy for the treatment of Y1R-overexpressed breast cancer.

3.
ACS Appl Mater Interfaces ; 13(46): 54770-54782, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34780685

RESUMO

Chemodynamic therapy (CDT), deemed as a cutting-edge antineoplastic therapeutic tactics, efficaciously suppresses tumors via catalytically yielding hydroxyl radicals (•OH) in tumor regions. Nevertheless, its biomedical applications are often restricted by the limited hydrogen peroxide (H2O2) level and upregulated antioxidant defense. Herein, a versatile nanoreactor is elaborately designed via integrating Cu2-xS and MnO2 for T1-weighted magnetic resonance (MR) imaging-guided CDT, synergistically enhanced through hypothermal ablation and oxidation resistance reduction, thereby displaying splendid antitumor efficiency as well as suppression on pulmonary metastasis. The as-synthesized Cu2-xS@MnO2 nanoreactors afford acid-dependent Cu-based and glutathione (GSH)-activated Mn-based catalytic properties for bimodal CDT. Owing to excellent absorbance at the second near-infrared (NIR-II) window, the Cu2-xS furnishes hypo-photo-thermal therapy (PTT) against tumor growth and ameliorates the catalytic performance for thermal-enhanced CDT. Additionally, MnO2 significantly downregulates GSH and glutathione peroxidase 4, which synergistically boosts CDT via promoting oxidative stress, simultaneously generating Mn2+ for MR contrast improvement and activatable tumor imaging. Therefore, this study proffers a new attempt centered on the collaborative strategy integrating NIR-II hypothermal PTT and synergistically enhanced CDT for tumor eradication.

4.
Nanoscale ; 13(45): 18912-18924, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34757354

RESUMO

With over millions of years of evolution, viruses can infect cells efficiently by utilizing their unique structures. Similarly, the drug delivery process is designed to imitate the viral infection stages for maximizing the therapeutic effect. From drug administration to therapeutic effect, nanocarriers must evade the host's immune system, break through multiple barriers, enter the cell, and release their payload by endosomal escape or nuclear targeting. Inspired by the virus infection process, a number of virus-like nanosystems have been designed and constructed for drug delivery. This review aims to present a comprehensive summary of the current understanding of the drug delivery process inspired by the viral infection stages. The most recent construction of virus-inspired nanosystems (VINs) for drug delivery is sorted, emphasizing their novelty and design principles, as well as highlighting the mechanism of these nanosystems for overcoming each biological barrier during drug delivery. A perspective on the VINs for therapeutic applications is provided in the end.


Assuntos
Nanopartículas , Preparações Farmacêuticas , Vírus , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Endossomos
5.
Nanoscale ; 13(45): 19085-19097, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34761764

RESUMO

Polypyrrole (PPy) nanoparticles have been widely studied in tumor photothermal therapy (PTT) for their significant photostability, good biocompatibility, and excellent photothermal performance. Herein, we report bovine serum albumin (BSA) stabilized PPy that were mineralized by MnO2 nanozyme on the surface (PPy@BSA-MnO2) to achieve synergistic photothermal and chemodynamic therapy (CDT) for breast cancer. In this multifunctional nanoplatform, the surface-loaded MnO2 undergoes a redox reaction with glutathione (GSH) to generate glutathione disulfide (GSSG) and Mn2+. Then, Mn2+ can convert H2O2 into a highly cytotoxic ˙OH to achieve chemodynamic therapy (CDT) and possess good magnetic resonance (MR) T1-weighted imaging capabilities to realize contrast imaging of the 4T1 tumor-bearing mouse models. In addition, PPy nanoparticles can efficiently convert near-infrared light energy into heat and achieve PTT. Most importantly, PPy@BSA-MnO2 nanoprobes have excellent in vitro 4T1 cell-killing effect and in vivo tumor-suppressive properties. The acute toxicity assessment results indicate that PPy@BSA-MnO2 nanoprobes have good biological safety. Therefore, the as-prepared multifunctional PPy@BSA-MnO2 nanoprobes possess excellent performance to promote MRI-guided PTT/CDT synergistic therapy for breast cancer treatment and have extensive clinical transformation and application prospects.


Assuntos
Neoplasias , Polímeros , Animais , Peróxido de Hidrogênio , Imageamento por Ressonância Magnética , Compostos de Manganês , Camundongos , Óxidos , Pirróis , Nanomedicina Teranóstica
6.
ChemMedChem ; 2021 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-34806311

RESUMO

Magnetic hyperthermia (MHT) uses magnetic iron oxide nanoparticles (MIONs) to irradiate heat when subjected to an alternating magnetic field (AMF), which then trigger a series of biological effects to realize rapid tumor-killing effects. With the deepening in research, MHT has also shown significant potential in achieving antitumor immunity. On the other hand, immunotherapy in cancer treatment has gained increasing attention over recent years and excellent results have generally been reported. Using MHT to activate antitumor immunity and clarifying its synergistic mechanism, i. e., immunogenic cell death (ICD) and immunosuppressive tumor microenvironment (TME) reversal, can achieve a synergistically enhanced therapeutic effect on primary tumors and metastatic lesions, and this can prevent cancer recurrence and metastasis, which thus prolong survival. In this review, we discussed the role of MHT when utilized alone and combining MHT with other treatments (such as radiotherapy, photodynamic therapy, and immune checkpoint blockers) in the process of tumor immunotherapy, including antigen release, dendritic cells (DCs) maturation, and activation of CD8+ cytotoxic T lymphocytes. Finally, the challenges and future development of current MHT and immunotherapy are discussed.

7.
Protein Pept Lett ; 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34792001

RESUMO

BACKGROUND: NIMA (never in mitosis, gene A) serine/threonine kinase 7 (NEK7) is a regulator of mitosis spindle in mammals and is considered as a drug target of inflammasome related inflammatory diseases. However, most commercially available or reported recombinant NEK7 proteins are either inactive or have low purity. These shortcomings limit the pharmacological studies and development of NEK7 inhibitors. OBJECTIVE: To elucidate what causes the NEK7 low purity in E. coli, and optimize a protocol to improve the protein purity. METHODS: A comparative study of expression full length NEK7 with an N-terminal His-tag or a Cterminal His-tag was performed. His-affinity resin, ion exchange and gel filtration chromatography were used to purify NEK7. The protein was identified by mass spectrometry. The activity and folding of NEK7 were evaluated by chemiluminescent assay and thermal shift assay. RESULTS: Our results demonstrated that N-terminal tagged protein was toxic to E. coli, resulting in incomplete translated products. The C-terminal tagged NEK7-His6 had a much higher purity than that of an N-terminal tag. The Ni2+ resin one-step purification led to a purity of 91.7%, meeting the criteria of most kinase assays. With two-step and three-step procedures, the protein purities were 94.7% and ~100%, respectively. The NEK7 purified in this work maintained its kinase activity and correct conformation, and the compound-protein interaction ability. CONCLUSION: Our optimized protocol could produce good purity of His tagged NEK7 in E. coli, and the kinase activity and biophysical characteristics of which are preserved.

8.
Nucleic Acids Res ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34792145

RESUMO

DNA methylation has a growing potential for use as a biomarker because of its involvement in disease. DNA methylation data have also substantially grown in volume during the past 5 years. To facilitate access to these fragmented data, we proposed DiseaseMeth version 3.0 based on DiseaseMeth version 2.0, in which the number of diseases including increased from 88 to 162 and High-throughput profiles samples increased from 32 701 to 49 949. Experimentally confirmed associations added 448 pairs obtained by manual literature mining from 1472 papers in PubMed. The search, analyze and tools sections were updated to increase performance. In particular, the FunctionSearch now provides for the functional enrichment of genes from localized GO and KEGG annotation. We have also developed a unified analysis pipeline for identifying differentially DNA methylated genes (DMGs) from the original data stored in the database. 22 718 DMGs were found in 99 diseases. These DMGs offer application in disease evaluation using two self-developed online tools, Methylation Disease Correlation and Cancer Prognosis & Co-Methylation. All query results can be downloaded and can also be displayed through a box plot, heatmap or network module according to whichever search section is used. DiseaseMeth version 3.0 is freely available at http://diseasemeth.edbc.org/.

9.
Biomater Sci ; 9(22): 7591-7602, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34668000

RESUMO

Photothermal therapy (PTT), as a promising antineoplastic therapeutic strategy, has been harnessed to restrain tumor growth through near-infrared (NIR) irradiation mediated thermal ablation. Nevertheless, its biological applications are hampered by thermal diffusion and up-regulated heat shock proteins (HSPs). Herein, a versatile nanotheranostic agent is developed via integrating Zn0.2Fe2.8O4 nanoparticles (NPs), polydopamine (PDA), and MnO2 NPs for T1/T2 dual-modal magnetic resonance (MR) imaging-guided and self-augmented PTT. The as-designed Zn0.2Fe2.8O4@PDA@MnO2 NPs adequately serve as a PTT agent to realize effective photothermal conversion and obtain local hyperthermia. Additionally, the Zn0.2Fe2.8O4@PDA@MnO2 NPs can significantly consume overexpressed glutathione (GSH) and generate Mn2+ in the tumor microenvironment (TME), thus destroying redox homeostasis and catalytically generating hydroxyl radicals (˙OH) for HSP suppression and PTT enhancement. Meanwhile, Mn2+ and Zn0.2Fe2.8O4 NPs significantly strengthen T1- and T2-weighted MR contrast for tumor imaging and PTT guidance. Hence, this study offers proof of concept for self-augmented PTT and T1/T2 dual-modal MR imaging for tumor elimination.


Assuntos
Hipertermia Induzida , Nanopartículas , Imageamento por Ressonância Magnética , Compostos de Manganês , Óxidos , Terapia Fototérmica , Nanomedicina Teranóstica , Microambiente Tumoral
10.
Nanotechnology ; 33(5)2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34700307

RESUMO

Tumor multidrug resistance (MDR) is a phenomenon in which drug-resistant tumor cells are resistant to multiple other unexposed antitumor drugs with different structures and targets. MDR of cancer is a primary cause of clinical chemotherapy failure. With the progress of nanotechnology in the medical field, more and more research works have developed many nanotechnology-based strategies to challenge drug resistance. This review details the recent studies at the National Center for Nanoscience and Technology utilizing various nanochemotherapy strategies for overcoming chemotherapy resistance of tumor. We discuss the benefits and limitations of the diverse strategies, as well as possible ways to overcome these limitations. Importantly, in order to combat cancer chemotherapy resistance with nanomedicine, the mechanisms of drug endocytosis and subsequent fate need to be explored and focused on. In the meanwhile, due to the complexity and diversity of chemotherapy resistance mechanisms, the development of more intelligent and controllable nanodrugs may have greater scope for clinical application.

11.
FASEB J ; 35(11): e21959, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34605572

RESUMO

The proliferation and migration of vascular smooth muscle cells (VSMCs) are essential events in venous neointimal hyperplasia (VNH), a culprit of arteriovenous fistula (AVF) malfunction. Mitotic arrest-deficient protein 2B (MAD2B) is a critical regulator of cell proliferation and differentiation in many scenarios. To address the role of MAD2B in VSMCs proliferation and migration during VNH, AVFs from patients with end-stage renal disease (ESRD) and chronic kidney disease (CKD) mice were used to evaluate MAD2B expression. In cultured VSMCs treated with platelet-derived growth factor-BB (PDGF-BB), the effect of MAD2B on VSMCs proliferation and migration was detected by cell counting kit-8 (CCK8) assay, immunofluorescence, wound-healing scratch and transwell assays. Besides, we exploited different small interfering RNAs (siRNAs) to explore the potential mechanisms in the issue. Furthermore, rapamycin was applied to reveal whether MAD2B-associated pathways were involved in its inhibitory effect on VSMCs proliferation and migration. Accordingly, we found that MAD2B expression was enhanced in AVFs from patients with ESRD, CKD mice and VSMCs stimulated by PDGF-BB. Meanwhile, inhibition of MAD2B alleviated VSMCs proliferation and migration while the number of ski-related novel gene (SnoN)-positive VSMCs was also increased in vivo and in vitro. Moreover, gene deletion of MAD2B decreased the level of SnoN protein in PDGF-BB-stimulated VSMCs. Furthermore, rapamycin suppressed the increased expressions of MAD2B and SnoN induced by PDGF-BB. Thus, our study demonstrates that inhibition of MAD2B suppresses the proliferation and migration of VSMCs during VNH via reducing SnoN expression. Moreover, rapamycin exerts an inhibitory effect on intimal hyperplasia, possibly via the MAD2B-SnoN axis.


Assuntos
Hiperplasia , Falência Renal Crônica/metabolismo , Proteínas Mad2/fisiologia , Neointima , Animais , Movimento Celular , Proliferação de Células , Células Cultivadas , Humanos , Hiperplasia/metabolismo , Hiperplasia/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Neointima/metabolismo , Neointima/patologia
12.
Biomaterials ; 278: 121139, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34624753

RESUMO

Peptide drug conjugate (PDC) has emerged as one of the new generations of targeted therapeutics for cancer, which owns the advantages of improved drug targetability and reduced adverse effects compared with traditional chemotherapy. However, the poor permeability of PDC drugs regarding tumor cells is an urgent problem to be solved. Herein, we design a PDC drug molecule, which is composed of three modules: targeting motif (RGD target), assembly motif (GNNNQNY) and cytotoxic payload (CPT molecule). This PDC in situ forms nanoclusters upon binding cellular receptor, resulting in improved PDC cell-entry efficiency and treatment efficacy. In addition, the PDC shows increased therapeutic efficacy and raises the maximum tolerance dose of the drug in breast and bladder xenografted mice models. This strategy leverages the assembly principle to promote penetration of peptide molecules into cells and increase intracellular drug bioavailability, which is of great significance for the development of PDC drugs in the future.


Assuntos
Antineoplásicos , Preparações Farmacêuticas , Animais , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Camundongos , Peptídeos
13.
Curr Drug Metab ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34602032

RESUMO

BACKGROUND: Hepatocellular damage has been reported for the antimalarial piperaquine (PQ) in the clinic after cumulative doses. OBJECTIVES: The role of metabolism in PQ toxicity was evaluated, and the mechanism mediating PQ hepatotoxicity was investigated. METHOD: The toxicity of PQ and its major metabolite (PQ N-oxide; M1) in mice was evaluated in terms of serum biochemical parameters. The role of metabolism in PQ toxicity was investigated in mice pretreated with an inhibitor of CYP450 (ABT) and/or FMO enzyme (MMI). The dose-dependent pharmacokinetics of PQ and M1 were studied in mice. Histopathological examination was performed to reveal the mechanism mediating PQ hepatotoxicity. RESULTS: Serum biochemical levels (ALT and BUN) increased significantly (P < 0.05) in mice after three-day oral doses of PQ (> 200 mg/kg/day), indicating hepatotoxicity and nephrotoxicity of PQ at a high dose. Weaker toxicity was observed for M1. Pretreatment with ABT and/or MMI did not increase PQ toxicity. PQ and M1 showed linear pharmacokinetics in mice after a single oral dose, and multiple oral doses led to their cumulative exposures. Histopathological examination showed that a high dose of PQ (> 200 mg/kg/day for three days) could induce hepatocyte apoptosis. The mRNA levels of targets in NF-κB and p53 pathways could be up-regulated by 2-30-fold in mice by PQ or M1. CONCLUSIONS: PQ metabolism led to detoxification of PQ, but there was a low possibility of altered toxicity induced by metabolism inhibition. The hepatotoxicity of PQ and its N-oxidation metabolite was partly mediated by NF-κB inflammatory pathway and p53 apoptosis pathway.

14.
J Asian Nat Prod Res ; : 1-7, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34605341

RESUMO

One new ionone glycoside, named centrantheroside F (1), together with 9 known compounds (2-10), were isolated from the roots of Centranthera grandiflora. Their structures were determined by spectroscopic data analyses and comparing with the literature data. The absolute configuration of 1 was confirmed via 2 D NMR and electronic circular dichroism (ECD). All isolated compounds were evaluated for their inhibitory activity on lipopolysaccharide (LPS)-induced nitric oxide (NO) production.

15.
Appl Opt ; 60(21): 6030-6043, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34613267

RESUMO

White light interferometry is a well-established surface recovery technique. In this paper, a white light signal processing algorithm based on phase error compensation using spectrum selection is proposed. The derived nonlinear phase distribution from the correlogram is modeled as the combination of random errors and systemic deviations. By developing a new, to the best of our knowledge, recovery algorithm, the phase noise can be separated from the linear map and significantly attenuated. Based on the proposed algorithm, the spectrum features of white light LEDs and halogen lamps are investigated in detail. The inner products defined by three selected points are employed to generate a coefficient to evaluate the linearity of an unwrapped phase map within a certain spectrum region. The optimal spectrum range corresponding to the best measurement performance can then be located where the coefficient approximates 1 and the spectrum energy stays relatively high. The simulations are carried out under different levels of SNR and scan step noises, which show that the new method can effectively reduce additional disturbance from the recovered topography. In experiments, the system with the proposed method is first calibrated by a step height standard (VLSI, 182.7±2.0nm) with the repeatability of 0.44 nm. A silicon wafer and three roughness standards are also tested to further verify the robustness of the new method.

16.
Natl Sci Rev ; 8(6): nwab068, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34691676

RESUMO

Liposomes, especially cationic liposomes, are the most common and well-investigated nanocarriers for biomedical applications, such as drug and gene delivery. Like other types of nanomaterials, once liposomes are incubated in a biological milieu, their surface can be immediately cloaked by biological components to form a protein corona, which confers a new 'biological identity' and modulates downstream interactions with cells. However, it remains unclear how the protein corona affects the transportation mechanism after liposomes interact with cells. Here, we employed home-made aggregation-induced-emission-visualized nanoliposomes TR4@Lipo as a model to investigate transportation with or without the protein corona by optical imaging techniques. The results show that the protein corona can change the cellular transportation mechanism of TR4@Lipo from energy-independent membrane fusion to energy-dependent endocytosis. The protein corona also modulates the intracellular distribution of loaded cargoes. This knowledge furthers our understanding of bio-nano interactions and is important for the efficient use of cationic liposomes.

17.
Nano Res ; : 1-30, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34659650

RESUMO

Vaccination is the most effective way to prevent coronavirus disease 2019 (COVID-19). Vaccine development approaches consist of viral vector vaccines, DNA vaccine, RNA vaccine, live attenuated virus, and recombinant proteins, which elicit a specific immune response. The use of nanoparticles displaying antigen is one of the alternative approaches to conventional vaccines. This is due to the fact that nano-based vaccines are stable, able to target, form images, and offer an opportunity to enhance the immune responses. The diameters of ultrafine nanoparticles are in the range of 1-100 nm. The application of nanotechnology on vaccine design provides precise fabrication of nanomaterials with desirable properties and ability to eliminate undesirable features. To be successful, nanomaterials must be uptaken into the cell, especially into the target and able to modulate cellular functions at the subcellular levels. The advantages of nano-based vaccines are the ability to protect a cargo such as RNA, DNA, protein, or synthesis substance and have enhanced stability in a broad range of pH, ambient temperatures, and humidity for long-term storage. Moreover, nano-based vaccines can be engineered to overcome biological barriers such as nonspecific distribution in order to elicit functions in antigen presenting cells. In this review, we will summarize on the developing COVID-19 vaccine strategies and how the nanotechnology can enhance antigen presentation and strong immunogenicity using advanced technology in nanocarrier to deliver antigens. The discussion about their safe, effective, and affordable vaccines to immunize against COVID-19 will be highlighted.

18.
J Mol Neurosci ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34471984

RESUMO

Polo-like kinase 4 (PLK4) is one of the key regulators of centrosomal replication. However, its role and mechanism in spinal cord injury (SCI) are still unclear. The SCI model on rats was constructed and the expression and localization of PLK4 in the spinal cord are analyzed with Western blot and immunofluorescence, respectively. Then the specific siRNAs were encapsulated in nanoparticles for the inhibition of PLK4 expression. Afterward, the role of PLK4 on astrocytes was investigated by knocking down its expression in the primary astrocytes. Moreover, siRNA-loaded nanoparticles were injected into the injured spinal cord of rats, and the motor function recovery of rats after SCI was assessed using the Basso, Beattie, and Bresnahan (BBB) locomotor scale method. Notably, the siRNA-loaded nanoparticles effectively transfect primary astrocytes and significantly inhibit PLK4 expression, together with the expression of PCNA with significance. After treatment, restoration of the motor function following SCI was significantly improved in the PLK4 knockdown group compared with the control group. Therefore, we speculate that inhibition of Plk4 may inhibit the proliferation of astrocytes and decrease the inflammatory response mediated by astrocytes, so as to promote the functional recovery of SCI. In conclusion, inhibition of PLK4 expression via siRNA-loaded nanoparticles may be a potential treatment for SCI.

19.
Biomaterials ; 277: 121126, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34544033

RESUMO

Many drugs must be administered intravenously instead of oral administration due to their poor oral bioavailability. The cost of repeated infusion treatment for 6 weeks every year is as high as tens of billions of dollars worldwide. Exosomes are nano-sized (30-150 nm) extracellular vesicles secreted by mammalian cells due to environmental stimulation or self-activation. Milk contains abundant exosomes originated from multiple cellular sources. It has been proved that milk exosomes (MEs) could survive with the strongly acidic conditions in the stomach and degradative conditions in the gut. Furthermore, they can cross biological barriers to reach targeted tissues. The ability of MEs to cross the gastrointestinal barrier makes them as a promising drug delivery tool for oral delivery. This review is devoted to the purification of MEs, their biocompatibility and immunogenicity, and prospects for their use as natural drug carriers for oral administration.


Assuntos
Exossomos , Administração Oral , Animais , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Leite
20.
Nat Commun ; 12(1): 5532, 2021 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-34545089

RESUMO

Isopropenyl ethers are critical intermediates for accessing medicinally valuable ketal-based prodrugs and biomaterials, but traditional approaches for the synthesis of isopropenyl ethers suffer from poor functional group compatibility and harsh reaction conditions. Here, we develop an organocatalytic transisopropenylation approach to solve these challenges, enabling the synthesis of isopropenyl ethers from various hydroxyl-group-containing small-molecule drugs, polymers, and functional building blocks. The method provides a straightforward and versatile synthesis of isopropenyl ethers, features excellent tolerance of diverse functional groups, applies to a wide range of substrates, and allows scalable synthesis. The development of this organocatalytic transisopropenylation approach enables access to modular preparation of various acid-sensitive ketal-linked prodrugs and functionalized ketalated biomaterials. We expect our syntheses and transformations of isopropenyl ethers will find utility in several diverse fields, including medicinal chemistry, drug delivery, and biomaterials.


Assuntos
Álcoois/química , Materiais Biocompatíveis/química , Prenilação , Pró-Fármacos/química , Células 3T3 , Acetona/química , Álcoois/síntese química , Animais , Catálise , Feminino , Células HCT116 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus
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