首页期刊导航|Acta biomaterialia
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Acta biomaterialia
Elsevier
Acta biomaterialia

Elsevier

1742-7061

Acta biomaterialia/Journal Acta biomaterialiaEIISTPSCI
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    Zn-dipicolylamine-based reactive oxygen species-responsive lipids for siRNA delivery and in vivo colitis treatment

    Guo Y.He X.Zhao R.-M.Yang H.-Z....
    12页
    查看更多>>摘要：? 2022 Acta Materialia Inc.The reduction of reactive oxygen species (ROS) and inflammatory factor levels plays an important role in the treatment of colitis. A series of ROS-responsive lipids (ZnDPA-R) based on the thioketal structure were designed and synthesized. It was expected that the lipidic materials could combine ROS consumption and siRNA delivery capacity to achieve synergistic treatment of colitis. The target liposomes could combine with the phosphate backbone of siRNA to form lipoplexes of size ～100 nm and could deliver siRNA cargo into the cell. The results of in vitro anti-inflammatory experiments showed that the lipids may effectively consume ROS in the cells. The lipoplexes significantly reduced the expression levels of TNF-α mRNA and related inflammatory factors in macrophages. After PEGylation, the lipoplex was used for treating mouse colitis, and the biodistribution results proved that the lipoplexes effectively aggregated in the intestine. The delivery system could not only respond to the high ROS level in colitis through breaking of thioketal structure, but it could also assist in treating inflammation by ROS consumption. The treatment results revealed that the levels of TNF-α mRNA and related inflammatory factors in the colon lesion were largely reduced, and the inflammatory symptoms were significantly relieved. Hematology test results indicated that the treatment was safe and induced no side effects in mice. The present study may shed light on the synergistic treatment of colitis through anti-inflammatory siRNA delivery and ROS depletion strategies. Statement of significance: Downregulation of inflammatory factors and reactive oxygen species (ROS) levels is critical in treating colitis. In the present study, a series of ROS-responsive lipid molecules based on the Zn-DPA headgroup and thioketal linkage were synthesized for delivering TNF-α siRNA and for treating colitis. In addition to silencing the expression of TNF-α mRNA and the related inflammatory factors, the material also achieved synergistic treatment by simultaneous consumption of ROS in the colon lesion. In vitro cell experiments and in vivo colitis treatment in mice showed that the lipoplex exerted a satisfactory therapeutic effect on colitis, and the symptoms of colitis in mice were significantly alleviated. The present study may shed light on the synergistic treatment for colitis through anti-inflammatory siRNA delivery and ROS depletion strategies.
      原文链接:
    • NSTL
    • Elsevier

    Active targeting redox-responsive mannosylated prodrug nanocolloids promote tumor recognition and cell internalization for enhanced colon cancer chemotherapy

    Gao Y.Qiu W.Liang M.Ma X....
    15页
    查看更多>>摘要：? 2022Despite the diversified therapeutic approaches for malignant tumors, chemotherapy remains the backbone of current cancer treatment. However, conventional chemotherapeutics was found to be associated with deficient recognition of tumor, low uptake efficiency, insolubility, short circulation, poor biocompatibility and low therapeutic outcomes. Herein, the active targeting redox-responsive mannosylated prodrug nanocolloids (HM NCs) were constructed for enhanced chemotherapy of colon cancer. HM NCs were prepared by the covalent cross-linking of 10-hydroxycamptothecin (HCPT) and mannose (MAN) via a redox-responsive cross-linker containing disulfide bonds, and modified with a moderate amount of polyethylene glycol (PEG). The large amount of mannose contained in HM NCs could actively target overexpressed mannose receptors on the surface of cancer cells and enhance cancer cell internalization through mannose receptor-mediated endocytosis. Owing to the combination of active targeting and the enhanced permeability and retention (EPR) passive targeting, HM NCs could effectively accumulate in tumors and high glutathione (GSH) in tumor microenvironment triggered cleavage of redox-responsive bonds and precise drug release. HM NCs exhibited superior antitumor activity both in vitro and in vivo and appreciably extended the mouse survival rate with good biocompatibility. The innovative HM NCs are expected to be conducive to overcoming the limitations of conventional chemotherapy for colon cancer and providing more choices for future clinical translation. Statement of significance: Despite the enhanced permeability and retention effect, the passive targeting can be interfered with by the complex biologic barriers in the body. In this study, an active targeting system (HM NCs) was constructed by covalent cross-linking of mannose and anticancer drug 10-hydroxycamptothecin via redox-responsive disulfide bonds for enhanced colon cancer chemotherapy. Mannosylation could promote hydrophilia and stability for prolonged blood circulation. Mannose could promote tumor recognition and cell internalization via mannose receptor-mediated endocytosis. High glutathione level could trigger the redox-responsive release of anticancer drugs and further induce cell apoptosis via DNA damage. The HM NCs exhibited superior antitumor activity both in vitro and in vivo and appreciably extended the mouse survival rate with good biocompatibility.
      原文链接:
    • NSTL
    • Elsevier

    Enhanced treatment of cerebral ischemia–Reperfusion injury by intelligent nanocarriers through the regulation of neurovascular units

    Ye L.Teng C.Cao X.Lu H....
    13页
    查看更多>>摘要：? 2022Reperfusion injury is one of the major causes of disability and death caused by ischemic stroke, and drug development focuses mainly on single neuron protection. However, different kinds of cells in the neurovascular units (NVUs), including neurons, microglia and vascular endothelial cells, are pathologically changed after cerebral ischemia–reperfusion injury, resulting in an urgent need to develop a drug delivery system to comprehensively protect the kinds of cells involved in the NVU. Herein, we have constructed a c(RGDyK) peptide modified, NF-κB inhibitor caffeic acid phenethyl ester (CAPE)-loaded and reactive nitrogen species (RNS) stimuli-responsive liposomal nanocarrier (R-Lipo-CAPE) to target ischemic lesions and then remodel the NVU to reduce the progression of cerebral ischemia–reperfusion injury. The R-Lipo-CAPE liposomes were approximately 170 nm with a zeta potential of -30.8 ± 0.2 mV. The in vitro CAPE release behavior from R-Lipo-CAPE showed an RNS-dependent pattern. For in vivo studies, transient middle cerebral artery occlusion/reperfusion (MCAO) model mice treated with R-Lipo-CAPE had the least neurological impairment and decreased brain tissue damage, with an infarct area of 13%, compared with those treated with saline of 53% or free CAPE of 38%. Furthermore, microglia in the ischemic brain were polarized to the tissue-repairing M2 phenotype after R-Lipo-CAPE treatment. In addition, R-Lipo-CAPE-treated mice displayed a prominent down-regulated expression of MMP-9 and restored expression of the tight junction protein claudin-5. This proof-of-concept indicates that R-Lipo-CAPE is a promising nanomedicine for the treatment of cerebral ischemia–reperfusion injury through the regulation of neurovascular units. Statement of significance: Based on the complex mechanism and difficulty in treatment of cerebral ischemia-reperfusion injury, the overall regulation of neurovascular unit has become an extremely important target. However, little nanomedicine has been directed to remodel the neurovascular units in targeted cerebral ischemia-reperfusion injury therapy. Here, c(RGDyK) peptide modified reactive nitrogen species (RNS) stimuli-responsive liposomal nanocarrier loaded with a NF-κB inhibitor (CAPE), was designed to simultaneously regulate various cells in the microenvironment of cerebral ischemia-reperfusion injury to remodel the neurovascular units. Our in vitro and in vivo data showed that the intelligent nanocarrier exerted the ability of pathological signal stimuli-responsive drug release, cerebral ischemia-reperfusion injury site targeting and neurovascular units remodeling through reducing neuron apoptosis, regulating microglia polarization and repairing vascular endothelial cell. Overall, the intelligent liposomal drug delivery system was a promising and safe nanomedicine in the perspective of cerebral ischemia-reperfusion injury treatment.
      原文链接:
    • NSTL
    • Elsevier

    An auto-photoacoustic melanin-based drug delivery nano-platform for self-monitoring of acute kidney injury therapy via a triple-collaborative strategy

    Zhao X.Sun J.Dong J.Guo C....
    15页
    查看更多>>摘要：? 2022 Acta Materialia Inc.Rhabdomyolysis-induced acute kidney injury (AKI) is closely related to toxic reactive oxygen species (ROS), apoptosis, and inflammation. Excessive activation of poly (ADP-ribose) polymerase-l (PARP-1) by ROS can cause mitochondrial dysfunction and release of the proapoptotic protein AIF, which triggers an intrinsic PARP-1-dependent cell death program. Considering these characteristics of rhabdomyolysis-induced AKI, we developed a targeting nanodrug delivery platform by loading PJ34 and coupling anti-GPR97 with melanin nanoparticles (GMP nanoparticles) that could realize photoacoustic self-monitoring and triple-collaborative treatment (antioxidant, antiapoptotic, and anti-inflammatory). The nanoparticles exhibited good dispersibility, solubility, and broad-spectrum ROS scavenging ability. In vitro experiments revealed high biocompatibility of the GMP nanoparticles and strong ability of scavenging multiple toxic ROS, antiapoptotic activity, and anti-inflammatory activity. Because melanin nanoparticles possess inherent photoacoustic (PA) imaging capability, they can not only serve as a drug carrier but also perform self-monitoring for real-time tracking of GMP biodistribution and renal uptake in a murine AKI model through PA imaging. In vivo experiments showed that the GMP nanoparticles could effectively reduce oxidative stress, apoptosis, and inflammatory response in mice with rhabdomyolysis-induced AKI, and the mechanism of alleviation was verified through western blot experiments. These results indicated that the nanoplatform could realize the targeted delivery and curative effect monitoring under the guidance of PA imaging, which is of great significance for the prevention and treatment of AKI. Statement of significance: A targeting nanodrug delivery platform was developed by loading PJ34 and coupling anti-GPR97 with melanin nanoparticles (GMP nanoparticles) for photoacoustic self-monitoring and triple-collaborative treatment (antioxidant, antiapoptotic, and anti-inflammatory) of acute kidney injury (AKI). Further studies indicated that the Keap-1/Nrf2/HO-1 and PARP-1/AIF signaling pathways are involved in the therapeutic mechanisms to alleviate AKI. Immunohistochemical staining and routine blood test confirmed the anti-inflammatory performance of GMP nanoparticles. Compared to exogenous nanomaterials, we used endogenous melanin with broad ROS scavenging capacity as the nanocarrier and antioxidant, which not only overcomes the defects of high specificity, potential toxicity, low loading capacity, and high cost but also shows good biosafety and photoacoustic imaging performance in vivo.
      原文链接:
    • NSTL
    • Elsevier

    VH298-loaded extracellular vesicles released from gelatin methacryloyl hydrogel facilitate diabetic wound healing by HIF-1α-mediated enhancement of angiogenesis

    Wang Y.Cao Z.Wei Q.Ma K....
    14页
    查看更多>>摘要：? 2022Endothelial malfunction is responsible for impaired angiogenesis in diabetic patients, thereby causing the delayed healing progress of diabetic wounds. Exosomes or extracellular vesicles (EVs) have emerged as potential therapeutic vectors carrying drug cargoes to diseased cells. In the present study, EVs were reported as a new treatment for diabetic wounds by delivering VH298 into endothelial cells. Firstly, EVs derived from epidermal stem cells (ESCs) were loaded with VH298 (VH-EVs), and the characteristics of VH-EVs were identified. VH-EVs showed promotive action on the function of human umbilical vein endothelial cells (HUVECs) in vitro by activating HIF-1α signaling pathway. VH-EVs were also found to have a therapeutic effect on wound healing and angiogenesis in vivo. We further fabricated gelatin methacryloyl (GelMA) hydrogel for sustained release of VH-EVs, which possessed high biocompatibility and proper mechanical properties. In diabetic mice, GelMA hydrogel containing VH-EVs (Gel-VH-EVs) effectively promoted wound healing by locally enhancing blood supply and angiogenesis. The underlying mechanism for enhanced angiogenesis was possibly associated with the activation of HIF-1α/VEGFA signaling pathway. Collectively, our findings suggest a promising EV-based strategy for the VH298 delivery to endothelial cells and provide a new bioactive dressing for diabetic wound treatment. Statement of significance: The angiogenic dysfunction is the main cause of diabetic wound unhealing. Extracellular vesicles (EVs) have been reported to be helpful but their efficacy is limited for angiogenesis in cutaneous regeneration. VH298 holds great promise to improve angiogenesis by stabilizing HIF-1α which is reported at low level in diabetic wounds. Here, we loaded EVs with VH298 (VH-EVs) to exert an on-target enhancement of proangiogenic capacity in diabetic wound. Then, we applied a photo-crosslinkable hydrogel, gelatin methacryloyl (GelMA) containing VH-EVs (Gel-VH-EVs) as a convenient biomaterial and an adaptable scaffold for sustained releasing VH-EVs. The results showed significant therapeutic effect of Gel-VH-EVs on skin defect repair. Our findings suggest a promising EVs-based drug delivery strategy and a new functional wound dressing for patients.
      原文链接:
    • NSTL
    • Elsevier

    Targeted delivery and enhanced uptake of chemo-photodynamic nanomedicine for melanoma treatment

    Huang X.Mu N.Ding Y.Lam H.W....
    10页
    查看更多>>摘要：? 2022Nanoparticles (NPs) modified with targeting ligands have often shown great potential in targeted drug delivery for tumor therapy. However, the clearance of NPs by the monocyte-phagocyte system (MPS) and the relatively low cellular uptake by tumor cells have significantly limited the antitumor efficacy of a variety of nanomedicines. Tumor microenvironment-mediated multidrug resistance also reduces the antitumor efficacy of internalized nanomedicines. Herein, we developed an innovative nanomedicine for combined chemo-photodynamic therapy of melanoma through targeted drug delivery and significantly improved the cellular uptake of the nanomedicine through the charge-reversal phenomenon. An amphiphilic platinum (IV)-polyethylenimine-chlorin e6 (Pt(IV)-PEI-Ce6) polymer was designed, prepared, and self-assembled into NPs (PPC) in an aqueous solution, and these NPs were subsequently coated with hyaluronic acid (HA) to afford PPC@HA. The surface-coated HA provided PPC with a negatively charged surface potential to reduce the clearance by the MPS during systemic circulation and enhanced the targeted delivery of PPC to CD44-overexpressing melanoma cells. Upon accumulation in the tumor site, hyaluronidase overexpressed in the tumor induced HA degradation to release the positively charged PPC, resulting in an increased internalization of PPC into tumor cells. Bioactive Pt(II) was released in response to high glutathione level in the tumor cells for effective tumor chemotherapy. Under 650 nm laser irradiation, Ce6 produced reactive oxygen species (ROS), thus driving photodynamic therapy. Finally, PPC@HA exhibited combined photodynamic-chemotherapeutic antitumor efficacy against the melanoma cells in mice. Statement of significance: Tumors are one of the greatest threats to human health, and chemotherapy has been one of the most common therapeutic modalities for treating tumors; however, many challenges related to chemotherapy remain, such as low delivery efficiency, side effects, and unsatisfactory therapeutic efficacy. Nanomedicines modified with targeting ligands have often shown great potential in improving targeted drug delivery for tumor therapy; however, the clearance of nanomaterials by the monocyte-phagocyte system and the relatively low cellular uptake by tumor cells have significantly limited the antitumor efficacy of a variety of nanomedicines. Herein, we developed a novel charge-reversal-based, hyaluronic acid-coated, Pt(IV) prodrug and chlorin e6-based nanomedicine to improve systemic circulation and targeted accumulation of the nanomedicine in the tumor tissue and to enhance its intracellular uptake. This nanomedicine may provide a potential new platform to improve the drug content inside tumor cells and to effectively inhibit tumor growth through combined chemotherapy and photodynamic therapy.
      原文链接:
    • NSTL
    • Elsevier

    A carrier-free photodynamic nanodrug to enable regulation of dendritic cells for boosting cancer immunotherapy

    Qin X.Zhang M.Zhao Z.Du Q....
    11页
    查看更多>>摘要：? 2022 Acta Materialia Inc.Immune response is initiated by dendritic cells (DCs), where the cross-presentation of antigens by DCs determines the activating of cytotoxic T cells. However, the efficacy of DCs-initiated immune response is governed by multiple (cascade) steps of immunogenic cell death (ICD), recruitment of DCs, and cross-presentation of DCs. It is urgent but challenging to achieve a platform for simultaneously regulating these multiple steps, amplifying the immune response against tumors. Herein, we reported a photodynamic nanodrug enabling simultaneous regulation of these multiple steps for realizing powerful immune response. The nanodrug was designed by the co-assembling of chlorin e6 (Ce6), celecoxib and 6-thio-2′-deoxyguanosine (6-thio-dG). In our nanodrug, Ce6 enables induction of ICD, while celecoxib down-regulates the prostaglandin E2 (PGE2) for promoting recruitment of DCs enabled by chemokine CCL5 produced from natural killer (NK) cells. Moreover, 6-thio-dG triggers DNA damages in the tumor cells, which in turn activates STING/interferon I pathway for enhancing the cross-presentation ability of DCs. Therefore, an amplified immune therapeutic effect against tumors is achieved, thanks to the simultaneous regulation of these multiple steps. The nanodrug effectively inhibits tumor growth and postoperative recurrence, demonstrating a new approach for boosting immune response initiated by DCs in cancer therapy. Statement of significance: The dendritic cells (DCs)-initiated immune response against tumors is dominated by multiple (cascade) steps including the process of (I) immunogenic cell death (ICD), (II) recruitment of DCs, and (III) cross-presentation of antigens by DCs. Based on this, it is urgent to design a nanoplatform enabling simultaneous regulation of these multiple steps for achieving a potent therapeutic efficacy. A carrier-free photodynamic nanodrug, engineered by a co-assembling approach, was designed to regulate DCs for realizing a powerful DCs-initiated immune response against tumors, thanks to the simultaneous regulation of the above multiple steps. Our nanodrug demonstrated a boosted immune response against tumors, powerfully suppressing primary/abscopal tumor growth and postoperative recurrence, which offers a conceptually innovative strategy for amplifying immunity against tumors.
      原文链接:
    • NSTL
    • Elsevier

    Continuous flow scale-up of biofunctionalized defective ZnO quantum dots: A safer inorganic ingredient for skin UV protection

    Sarkar S.Debnath S.K.Srivastava R.Kulkarni A.R....
    14页
    查看更多>>摘要：? 2022 Acta Materialia Inc.The versatility of ZnO quantum dots (QDs) exhibiting size-tunable visible photoluminescence has propelled them to the forefront of leading-edge innovations in healthcare. At the nano-bio interface, enhancing the singly-ionized oxygen vacancy defects (VO?) through holistic, sustainable synthesis protocols driven by the synergistic influence of QDs’ nucleation-growth kinetics has implications on their bioactivity, physiochemical, and optical performance. Recently, robust continuous flow platforms have transcended the conventional batch reactors by alleviating the concerns of “hot-spot” formation due to inhomogeneous heat distribution, acute energy consumption, poor quality, and yield. However, complexities exist in translating batch chemistries into flow processes. Here, a unique, rationally designed continuous flow synthesis of luminescent defect-engineered ZnO QDs (E-QDs) via helical-reactor assembly that can adequately synthesize on a large scale is reported. The crux of this lies in the amalgamation of “green chemistry” and flow synthesis, which results in Lamer-mechanism mediated monodispersed E-QDs demonstrating high photoluminescence quantum yield (PLQY) of 89% under an accurately regulated synthesis environment. Process intensification corroborated that the bio-stable E-QDs manifested admirable photostability, broad-spectrum UV-shielding (400–250 nm), colloidal stability, in vitro biocompatibility against L929 and HaCaT cells, and antioxidant activity. These attributes were better compared to the commercial ZnO nanoparticles (ZnOC-NPs) used for skin UV protection. Delving deeper, the main drivers for the high density of intrinsic VO? formation (Iv/Io～42.5) were revealed to be the reactor's hydrodynamic performance and the improvised heating rate (2.5°C/sec). Hence, these E-QDs have potential as a new, safe, and economical multifunctional active ingredient for skin UV protection and antioxidants for treating ROS-mediated disorders. Statement of significance: UV filters exhibiting questionable UV-attenuation efficacy and phototoxicity are significant impediments to the healthcare industry emphasizing skin cancer prevention. Although least explored, VO?-governed aberrant photoactive, biological, and surface-reactive qualities of engineered ZnO QDs (E-QDs) have created ample room to investigate these hallmarks for skin UV protection. However, the bottlenecks in stereotypical ZnO QDs production confined by inefficient process control are annihilated by continuous flow strategies. Herein, the high-throughput continuous flow helical reactor assembly was designed and fabricated to successfully showcase optimized transport properties, reproducibility, yield, and quality E-QDs. Anticipating a skyrocketing demand for E-QDs as bioactive-sunscreen components, the comprehensive investigation has demonstrated unprecedented biofunctionality and ROS-scavenging behaviour, even upon UVR exposure, contrary to the traditional nanoparticulate ZnO UV filters.
      原文链接:
    • NSTL
    • Elsevier

    The influence of a biomimetic pulmonary surfactant modification on the in vivo fate of nanoparticles in the lung

    Qin L.Guan J.Mao S.Liu Q....
    12页
    查看更多>>摘要：? 2022 Acta Materialia Inc.Direct biomimetic modification of nanoparticles (NPs) with endogenous surfactants is helpful to improve the biocompatibility of NPs and avoid damage to the physiological function of the lung. Therefore, the objective of this study is to investigate the influence of biomimetic endogenous pulmonary surfactant phospholipid modification on the in vivo fate of NPs after lung delivery. Here, two neutral phospholipids (dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylamine (DPPE)) and two negatively charged phospholipids (dipalmitoylphosphatidylglycerol (DPPG), dipalmitoylphosphatidylserine (DPPS)) were selected to modify paclitaxel (PTX)-loaded PLGA NPs with different molar ratio. DPPC, DPPE, and DPPG improved mucoadhesion, in contrast, DPPS improved the mucus permeability of the NPs. Neutral DPPC and DPPE reduced, but negatively charged DPPS and DPPG increased the uptake by alveolar macrophages, all types of phospholipid increased the uptake by lung epithelial cells and increased PTX retention in the whole lung. Whereas, DPPC, DPPE, and DPPG promoted PTX retention in bronchoalveolar lavage fluid (BALF), while DPPS promoted PTX absorption in the lung tissue. Only DPPS-PLGA (1:1) NPs remarkably increased PTX systemic exposure. A good correlation between PTX percentage in the supernatant of BALF and PTX concentration in plasma was established, implying PTX entered the system circulation mainly in molecular form. Phospholipid modification had no effect on extrapulmonary organ distribution of PTX. Taken together, our study disclosed that different phospholipid modification can endow the NPs mucoadhesive or mucus penetration and cellular uptake properties, with tunable retention in BALF and absorption in the lung tissue, providing the scientific background for translational nanocarrier design for inhalation as required. Statement of significance: Inhaled nanomedicines will inevitably interact with pulmonary surfactant and form “surfactant corona”. However, the contribution of individual pulmonary surfactant phospholipid on the in vivo fate of nanomedicines is still unclear. In this regard, the most abundant pulmonary surfactant phospholipid dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylamine, and dipalmitoylphosphatidylglycerol and dipalmitoylphosphatidylserine were selected to modify the paclitaxel loaded PLGA nanoparticles and the effect of these pulmonary surfactant phospholipids on their in vivo fate was investigated. It was demonstrated that different phospholipid modification can endow the nanoparticles mucoadhesive or mucus penetration properties, with tunable retention in bronchoalveolar lavage fluid, alveolar macrophages uptake and absorption in the lung tissue. The present study provided a comprehensive understanding for the role of pulmonary surfactant phospholipid on inhaled nanomedicines.
      原文链接:
    • NSTL
    • Elsevier

    Aspect Ratio of PEGylated Upconversion Nanocrystals Affects the Cellular Uptake In Vitro and In Vivo

    Wen S.Morsch M.Wang G.Zhou Z....
    11页
    查看更多>>摘要：? 2022The central nervous system (CNS) is protected by the blood-brain barrier (BBB), which acts as a physical barrier to regulate and prevent the uptake of endogenous metabolites and xenobiotics. However, the BBB prevents most non-lipophilic drugs from reaching the CNS following systematic administration. Therefore, there is considerable interest in identifying drug carriers that can maintain the biostability of therapeutic molecules and target their transport across the BBB. In this regard, upconversion nanoparticles (UCNPs) have become popular as a nanoparticle-based solution to this problem, with the additional benefit that they display unique properties for in vivo visualization. The majority of studies to date have explored basic spherical UCNPs for drug delivery applications. However, the biophysical properties of UCNPs, cell uptake and BBB transport have not been thoroughly investigated. In this study, we described a one-pot seed-mediated approach to precisely control longitudinal growth to produce bright UCNPs with various aspect ratios. We have systematically evaluated the effects of the physical aspect ratios and PEGylation of UCNPs on cellular uptake in different cell lines and an in vivo zebrafish model. We found that PEGylated the original UCNPs can enhance their biostability and cell uptake capacity. We identify an optimal aspect ratio for UCNP uptake into several different types of cultured cells, finding that this is generally in the ratio of 2 (length/width). This data provides a crucial clue for further optimizing UCNPs as a drug carrier to deliver therapeutic agents into the CNS. Statement of significance: The central nervous system (CNS) is protected by the blood-brain barrier (BBB), which acts as a highly selective semipermeable barrier of endothelial cells to regulate and prevent the uptake of toxins and pathogens. However, the BBB prevents most non-lipophilic drugs from reaching the CNS following systematic administration. The proposed research is significant because identifying the aspect ratio of drug carriers that maintains the biostability of therapeutic molecules and targets their transport across the blood-brain barrier (BBB) is crucial for designing an efficient drug delivery system. Therefore, this research provides a vital clue for further optimizing UCNPs as drug carriers to deliver therapeutic molecules into the brain.
      原文链接:
    • NSTL
    • Elsevier