Biomaterials Advances, Journal Year: 2022, Volume and Issue: 139, P. 213039 - 213039
Published: July 21, 2022
Language: Английский
Chinese Chemical Letters, Journal Year: 2022, Volume and Issue: 34(2), P. 107518 - 107518
Published: May 14, 2022
Language: Английский
Citations
346
Theranostics, Journal Year: 2022, Volume and Issue: 12(10), P. 4734 - 4752
Published: Jan. 1, 2022
Despite significant advances in research, the prognosis for both primary and secondary brain cancers remains poor.The blood-brain barrier (BBB) is a complex unique semi-permeable membrane that serves as protective structure to maintain homeostasis within brain.However, it presents challenge delivery of therapeutics into tumor.Some tumors are known compromise BBB integrity, producing highly heterogeneous vasculature blood-tumor-barrier (BTB).Identifying strategies bypass these obstacles improve penetrability anticancer has been focus research this area.In review, we discuss have investigated evade or alter cellular molecular barriers BTB detail methods currently under preclinical clinical investigation, including molecular, biological, physical processes overcome BTB.Increased understanding current overcoming will enable development new more effective treatment tumors.
Language: Английский
Citations
82
Small, Journal Year: 2022, Volume and Issue: 18(30)
Published: June 30, 2022
Abstract Alzheimer's disease (AD), as a progressive and irreversible brain disorder, remains the most universal neurodegenerative disease. No effective therapeutic methods are established yet due to hindrance of blood‐brain barrier (BBB) complex pathological condition AD. Therefore, multifunctional nanocarrier (Rapa@DAK/siRNA) for AD treatment is constructed achieve small interfering RNA β‐site precursor protein (APP) cleaving enzyme‐1 (BACE1 siRNA) rapamycin co‐delivery into brain, based on Aleuria aurantia lectin (AAL) β‐amyploid (Aβ)‐binding peptides (KLVFF) modified PEGylated dendrigraft poly‐ l ‐lysines (DGLs) via intranasal administration. Nasal administration provides an way deliver drugs directly through nose‐to‐brain pathway. AAL, specifically binding L‐fucose located in olfactory epithelium, endows Rapa@DAK/siRNA with high entry efficiency KLVFF peptide Aβ targeting ligand aggregation inhibitor enables nanoparticles bind Aβ, inhibit aggregation, reduce toxicity. Meanwhile, release BACE1 siRNA confirmed expression, promote autophagy, deposition. verified improve cognition transgenic mice after Collectively, potential avenue combination therapy
Language: Английский
Citations
76
Acta Pharmaceutica Sinica B, Journal Year: 2022, Volume and Issue: 12(6), P. 2658 - 2671
Published: Feb. 16, 2022
Glioma is a primary aggressive brain tumor with high recurrence rate. The poor efficiency of chemotherapeutic drugs crossing the blood‒brain barrier (BBB) well-known as one main challenges for anti-glioma therapy. Moreover, massive infiltrated tumor-associated macrophages (TAMs) in glioma further thwart drug efficacy. Herein, therapeutic nanosystem (SPP-ARV-825) constructed by incorporating BRD4-degrading proteolytic targeting chimera (PROTAC) ARV-825 into complex micelle (SPP) composed substance P (SP) peptide-modified poly(ethylene glycol)-poly(d,l-lactic acid)(SP-PEG-PDLLA) and methoxy acid) (mPEG-PDLLA, PP), which could penetrate BBB target tumor. Subsequently, released engenders antitumor effect via attenuating cells proliferation, inducing apoptosis suppressing M2 polarization through inhibition IRF4 promoter transcription phosphorylation STAT6, STAT3 AKT. Taken together, our work demonstrates versatile role efficacy SPP-ARV-825 against glioma, may provide novel strategy therapy future.
Language: Английский
Citations
73
ACS Nano, Journal Year: 2023, Volume and Issue: 17(23), P. 23746 - 23760
Published: Nov. 22, 2023
The increasing understanding of ferroptosis has indicated its role and therapeutic potential in cancer; however, this knowledge yet to be translated into effective therapies. Glioblastoma (GBM) patients face a bleak prognosis encounter challenges due the limited treatment options available. In study, we conducted genome-wide CRISPR–Cas9 screening presence inducer (RSL3) identify key driver genes involved ferroptosis. We identified ALOX15, lipoxygenase (LOX), as an essential Small activating RNA (saRNA) was used mediate expression ALOX15 promoted GBM cells. then coated saALOX15-loaded mesoporous polydopamine (MPDA) with Angiopep-2-modified macrophage membranes (MMs) reduce clearance by mononuclear phagocyte system (MPS) increase ability complex cross blood–brain barrier (BBB) during specific targeted therapy orthotopic GBM. These generated hybrid nanoparticles (NPs) induced mediating mitochondrial dysfunction rendering morphology abnormal. vivo, modified MM enabled NPs target cells, exert marked inhibitory effect on progression, promote radiosensitivity. Our results reveal promising suggest biomimetic strategy that depends biological properties MMs enhance vivo performance for treating
Language: Английский
Citations
71
Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(5), P. 612 - 612
Published: May 10, 2024
Overcoming the blood–brain barrier (BBB) remains a significant hurdle in effective drug delivery to brain. While BBB serves as crucial protective barrier, it poses challenges delivering therapeutic agents their intended targets within brain parenchyma. To enhance for treatment of neurological diseases, several technologies circumvent have been developed last few years. Among them, nanoparticles (NPs) are one most versatile and promising tools. Here, we summarize characteristics NPs that facilitate penetration, including size, shape, chemical composition, surface charge, importantly, conjugation with various biological or synthetic molecules such glucose, transferrin, insulin, polyethylene glycol, peptides, aptamers. Additionally, discuss coating surfactants. A comprehensive overview common vitro vivo models NP penetration studies is also provided. The discussion extends discussing impairment under pathological conditions leveraging alterations delivery. Emphasizing need future uncover inherent properties NPs, review advocates role beyond systems calls efforts translating clinic therapeutics. Overall, stand out highly strategy precise targeting disorders.
Language: Английский
Citations
23
ACS Nano, Journal Year: 2024, Volume and Issue: 18(8), P. 6445 - 6462
Published: Feb. 15, 2024
Tumor-associated macrophages (TAMs) are closely related to the progression of glioblastoma multiform (GBM) and its development therapeutic resistance conventional chemotherapy. TAM-targeted therapy combined with chemotherapy has emerged as a promising strategy combat GBM. However, presence blood–brain barrier (BBB) severely limits efficacy. Meanwhile, lack ability distinguish different targeted cells also poses challenge for precise therapy. Herein, we propose cathepsin B (CTSB)-responsive programmed brain-targeted delivery system (D&R-HM-MCA) simultaneous GBM-targeted delivery. D&R-HM-MCA could cross BBB via low density lipoprotein receptor-associated protein 1 (LRP1)-mediated transcytosis. Upon reaching GBM site, outer angiopep-2 modification be detached from cleavage CTSB-responsive peptide, which circumvent abluminal LRP1-mediated efflux. The exposed p-aminophenyl-α-d-mannopyranoside (MAN) further recognize glucose transporter-1 (GLUT1) on macrophage mannose receptor (MMR) TAMs. achieve chemotherapeutic killing simultaneously induce TAM polarization anti-inflammatory M2 phenotype pro-inflammatory M1 phenotype, thus resensitizing response improving anti-GBM immune response. This not only can improve brain efficiency, but enable combination chemo-immunotherapy against effectiveness this may provide thinking designing more functional systems effective regimens.
Language: Английский
Citations
17
Polymers, Journal Year: 2022, Volume and Issue: 14(4), P. 712 - 712
Published: Feb. 12, 2022
Nanotechnology has opened up a world of possibilities for the treatment brain disorders. Nanosystems can be designed to encapsulate, carry, and deliver variety therapeutic agents, including drugs nucleic acids. Nanoparticles may also formulated contain photosensitizers or, on their own, serve as photothermal conversion agents phototherapy. Furthermore, nano-delivery enhance efficacy contrast improved imaging diagnostics. However, effective is seriously hampered by formidable blood-brain barrier (BBB). Advances in understanding natural transport routes across BBB have led receptor-mediated transcytosis being exploited possible means nanoparticle uptake. In this regard, oligopeptide Angiopep-2, which high capacity, been utilized targeting ligand. Various organic inorganic nanostructures functionalized with Angiopep-2 direct diagnostic brain. Not only these shown great promise diagnosis cancer but they investigated injury, stroke, epilepsy, Parkinson's disease, Alzheimer's disease. This review focuses studies conducted from 2010 2021 Angiopep-2-modified nanoparticles aimed at
Language: Английский
Citations
62
Acta Pharmaceutica Sinica B, Journal Year: 2022, Volume and Issue: 12(8), P. 3354 - 3366
Published: March 17, 2022
Herein, we designed a dual-response shape transformation and charge reversal strategy with chemo-photodynamic therapy to improve the blood circulation time, tumor penetration retention, which finally enhanced anti-tumor effect. In system, hydrophobic photosensitizer chlorin e6 (Ce6), hydrophilic chemotherapeutic drug berberrubine (BBR) matrix metalloproteinase-2 (MMP-2) response peptide (PLGVRKLVFF) were coupled by linkers form linear triblock molecule BBR-PLGVRKLVFF-Ce6 (BPC), can self-assemble into nanoparticles. Then, positively charged BPC polyethylene glycol-histidine (PEG-His) mixed PEG-His@BPC negative surface long time. Due acidic microenvironment, PEG shell was detached from attributing protonation of histidine, achieved reversal, size reduction penetration. At same enzyme cutting site exposed, spherical nanoparticles could transform nanofibers following enzymolysis MMP-2, while BBR released kill tumors inducing apoptosis. Compared original nanoparticles, Ce6 retained within for longer Collectively, provided good example fully use intrinsic properties different drugs construct microenvironment-responsive transformable synergistic antitumor
Language: Английский
Citations
59
Advanced Science, Journal Year: 2022, Volume and Issue: 9(16)
Published: March 31, 2022
Abstract The blood–brain barrier (BBB) severely blocks the intracranial accumulation of most systemic drugs. Inspired by contribution bacterial outer membrane to Escherichia coli K1 (EC‐K1) binding and invasion BBB endothelial cells in meningitis, utilization ability EC‐K1 for brain‐targeted drug delivery construction a biomimetic self‐assembled nanoparticle with surface featuring lipopolysaccharide‐free are proposed. penetration nanoparticles is demonstrated occur through transcellular vesicle transport pathway, which at least partially dependent on internalization, endosomal escape, transcytosis mediated interactions between protein A gp96 cells. This nanoengineering strategy endows loaded drugs prolonged circulation, interstitial distribution, extremely high biocompatibility. Based critical roles cancer biology, this reveals enormous potential delivering therapeutics treat gp96‐overexpressing malignancies.
Language: Английский
Citations
53