Nano Today
·
2024
·
IF 13.2
Yang Xu,Ge Yan,Jingyu Zhao,Yunhao Ren,Qiyao Xiao,Minhong Tan,Lihua Peng
Cell heterogeneous nanomaterials based therapeutic strategies for Parkinson’s disease (PD) have been widely investigated, however, challenged by the potential toxicity, immunogenicity, limited drug loading efficiency, and restricted penetration through biological barriers. Herein, for the first time, a medicinal plant, Pueraria lobata derived exosomes (Pu-Exos) were demonstrated with excellent capability in overcoming cellular membrane and endosomal barriers, ensuring the efficient delivery of incorporated biomacromolecule cargos to SH-SY5Y cells. Upon that, Pu-Exos comprehensively improved the mitochondrial dysfunction of SH-SY5Y cells through removing dysfunctional mitochondria via PINK1-Parkin mediated mitophagy, and restoring ATP supplementation by preserving the activities of mitochondrial respiratory chain complexes I and V. Pu-Exos were then engineered with the ternary ligand, DSPE-PEG-RVG, forming Pu-Exos-PR that were further optimized for the cellular uptake and brain enrichment in vivo , therefore excellently promoting the survival of dopaminergic neurons, with reduced cellular degeneration, denser Nissl substance and increased tyrosine hydroxylase expression, accompanied by obviously alleviated motor and non-motor symptoms. Pu-Exos-PR were shown as a promising exosome with outstanding biocompatibility, efficient incorporation of bioactive agents, and unique feature in penetration through both nasal tissue and blood brain barrier, inaugurating new avenues to brain-targeting delivery for biomacromolecules for PD therapy. This study also casts new insight on the plant-derived exosomes as next generation of cell homogenous nanoplatforms with high efficiency and biosafety for drug delivery and therapy of brain diseases.
研究领域:
神经科学
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药学
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分子生物学
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生物技术
✓ 已验证
产品关联
DOI
高影响因子
BIOMATERIALS
·
2017
·
IF 8.402
Na Zhao,Baoyan Wu,Xianglong Hu,Da Xing
Stimuli-responsive nanoparticles with multiple therapeutic/diagnostic functions are highly desirable for effective tumor treatment. Herein novel caspase-3 responsive functionalized upconversion nanoparticles (CFUNs) were fabricated with three-in-one functional integration: near-infrared (NIR) triggered photodynamic damage along with caspase-3 activation, subsequent caspase-3 responsive drug release, and cascade chemotherapeutic activation. CFUNs were formulated from the self-assembly of caspase-3 responsive doxorubicin (DOX) prodrug tethered with DEVD peptide (DEVD-DOX), upconversion nanoparticles (UCNP), a photosensitizer (pyropheophorbide-a methyl ester, MPPa), and tumor-targeting cRGD-PEG-DSPE to afford multifunctional CFUNs, MPPa/UCNP-DEVD-DOX/cRGD. Upon cellular uptake and NIR irradiation, the visible light emission of UCNP could excite MPPa to produce reactive oxygen species for photodynamic therapy (PDT) along with the activation of caspase-3, which further cleaved DEVD peptide to release DOX within tumor cells, thus accomplishing NIR-triggered PDT and cascade chemotherapy. CFUNs presented silent therapeutic potency and negligible cytotoxicity in the dark, whereas in vitro and in vivo experiments demonstrated the NIR-triggered cascade therapeutic activation and tumor inhibition due to consecutive PDT and chemotherapy. Current NIR-activated cascade tumor therapy with two distinct mechanisms is significantly favorable to overcome multidrug resistance and tumor heterogeneity for persistent tumor treatment.
研究领域:
纳米技术
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癌症治疗
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药学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2024
·
IF 6.9
Sikai Deng,Weiwei Li,Qiyu Chen,Jianqun Shao,Junbo Zhang,Yuji Wang,Yinghuan Li
The mucus layer and intestine epithelium pose challenges to the bioavailability of orally administered paclitaxel (PTX). A novel P-glycoprotein inhibitor, (S)-2-decanoylamino-3-(1-naphthyl)propionyl-leucyl-valine (PgpI), was synthesized in this study. Its structure was characterized using 1 H NMR, 13 C NMR, ESI-MS and IR spectroscopies. The efficacy and in vivo toxicity of PgpI were comprehensively evaluated by R8-PEG@PLs&PgpI, i.e. , the oral combination of PgpI and octaarginine R8-PEG-DSPE modified PTX liposomes (R8-PEG@PLs), for lung cancer treatment. The joint forms between PgpI and R8-PEG@PLs were investigated and the affinity of PgpI for intestinal P-glycoprotein remained unaffected when combined externally with R8-PEG@PLs (R8-PEG@PLs&PgpI), compared to the diminished affinity for internal combination. The primary endocytic pathway for R8-PEG@PLs&PgpI in Caco-2 cells was the lipid raft, with increased percentage of macropinocytosis compared to unmodified PTX liposomes (PLs). The established physiology-based cellular kinetic models revealed that the net internalization rate of PTX was 2.3 times higher in R8-PEG@PLs&PgpI than in PLs, correlating with in vivo 2.2 times of antitumor rate. R8-PEG@PLs&PgpI may address the deficits of PLs in human lung A549 tumor-bearing mice due to the lower drug concentration than in normal mice. The external combination of R8-PEG@PLs&PgpI, offering maximal efficacy and security of PgpI, is promising for oral PTX delivery.
研究领域:
药学
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肿瘤学
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药物递送系统
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2024
·
IF 6.9
Yufei Pan,Yuejie Zhu,Yuan Ma,Jiamei Hong,Wenting Zhao,Yujing Gao,Jing Guan,Runan Ren,Qi Zhang,Jing Yu,Zhu Guan,Zhenjun Yang
Nucleic acid drugs are attracting significant attention as prospective therapeutics. However, their efficacy is hindered by challenges in penetrating cell membranes and reaching target tissues, limiting their applications. Nucleotidyl lipids, with their specific intermolecular interactions such as H-bonding and π-π stacking, offer a promising solution as gene delivery vehicles. In this study, a novel series of nucleotide-based amphiphiles were synthesized. These lipid molecules possess the ability to self-assemble into spherical vesicles of appropriate size and zeta potential in aqueous solution. Furthermore, their complexes with oligonucleotides demonstrated favorable biocompatibility and exhibited antiproliferative effects against a broad range of cancer cells. Additionally, when combined with the cationic lipid CLD, these complexes displayed promising in vitro performance and in vivo efficacy. By incorporating DSPE-PEGylated cRGD into the formulation, targeted accumulation of siG12D in pancreatic cancer cells increased from approximately 6% to 18%, leading to effective treatment outcomes (intravenous administration, 1 mg/kg). This finding holds significant importance for the liposomal delivery of nucleic acid drugs to extrahepatic tissues.
研究领域:
药学
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癌症治疗
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纳米技术
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
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2022
·
IF 12.545
Shulong Wang,Yanni Luo,Changchun Wen,Shulin Zhao,Liangliang Zhang
In situ visualization for the diagnosis of diabetic syndrome and visual monitoring the response to drug treatment is a challenge. Herein, we designed and prepared an autocatalytically-activatable hydrogen peroxide photoacoustic (PA) sensor. We first prepared the FeMoO x nanoparticle with catalase activity, then combined it to 2,2′-azino-bis(3-ethylbenzothi-azoline-6-sulfonic acid) (ABTS) and distearoylphos-phoethanola-mine-polyethylene-glycol (DSPE-PEG) to construct a autocatalytically-activatable PA sensor (FeMoO x @ABTS@DSPE-PEG). In its presence, ABTS can be converted into oxidized ABTS · + by H 2 O 2 . ABTS · + exhibits strong light absorption in the near-infrared region, and can serve as an ideal contrast agent for PA imaging. H 2 O 2 as a biomarker of oxidative stress response is closely related to the occurrence and development of diabetes mellitus and its complications. Therefore, FeMoO x @ABTS@DSPE-PEG was used as a PA sensor of H 2 O 2 for visual monitoring of the progression of diabetes-induced liver injury and metformin-mediated treatment of diabetes. The autocatalytically-activatable PA sensor developed in this study provides a promising platform for in situ visual diagnosis of diabetes and its syndrome and monitoring the response to therapy.
研究领域:
生物医学工程
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医学影像学
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糖尿病研究
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纳米技术
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL LETTERS
·
2022
·
IF 2.267
Xu-Feng Wang,Qiang Wang,Ying-Xia Zhang,Jin-Lan Yang,Dong-Hao Zhao
A sensitive and efficient magnetic amino modified multi-walled carbon nanotubes (m-MWCNT-NH2)-based magnetic dispersive solid-phase extraction (m-dSPE) coupled with hydrophilic interaction liquid chromatography–tandem mass spectrometry (HILIC-MS/MS) strategy is reported for the simultaneous determination of 13 paralytic shellfish toxins (PSTs) in bivalve mollusks. The samples were extracted twice with 1% acetic acid and purified using optimized m-dSPE procedures with Fe3O4 coated MWCNT-NH2 composites as magnetic adsorbents. The adsorbed PSTs on the m-MWCNT-NH2 adsorbents were separated using a Ni-coated neodymium magnet and subsequently eluted with 2 mL water–acetonitrile–acetic acid (80:20:1, v/v/v) and analyzed by HILIC-MS/MS. The correlation coefficients (r) of the targeted toxins obtained in matrix-matched external standard curves were from 0.997 to 0.999. The PSTs were acquired and quantified in the multiple reaction-monitoring mode and the limits of detection and quantitation in bivalve mollusks were 1.10 to 4.51 μg/kg and 3.67 to 13.5 μg/kg, respectively. Spiked recoveries at three concentrations in negative samples were from 73.4% to 92.5% with precision less than 10.6%. The method validation was in accordance with 2002/657/EC guidelines and method application in commercial bivalve mollusk samples. The developed method was rapid, convenient and economical for the determination of the targeted toxins.
研究领域:
分析化学
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食品安全
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毒理学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Science
·
2017
·Vol. 4
·期 4
·1600166
·
IF 9.034
Tingting Li,Dongliang Yang,Liuqing Zhai,Suiliang Wang,Baomin Zhao,Nina Fu,Lianhui Wang,Youtian Tao,Wei Huang
The fluorophores with long-lived fluorescent emission are highly desirable for time-resolved fluorescence imaging (TRFI) in monitoring target fluorescence. By embedding the aggregates of a thermally activated delayed fluorescence (TADF) dye, 2,3,5,6-tetracarbazole-4-cyano-pyridine (CPy), in distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol) (DSPE-PEG2000) matrix, CPy-based organic dots (CPy-Odots) with a long fluorescence lifetime of 9.3 μs (in water at ambient condition) and high brightness (with an absolute fluorescence quantum efficiency of 38.3%) are fabricated. CPy-Odots are employed in time-resolved and confocal fluorescence imaging in living Hela cells and in vivo. The green emission from the CPy-Odots is readily differentiated from the cellular autofluorescence background because of their stronger emission intensities and longer lifetimes. Unlike other widely studied DSPE-PEG2000 encapsulated Odots which are always distributed in cytoplasm, CPy-Odots are located mainly in plasma membrane. In addition, the application of CPy-Odots as a bright microangiography agent for TRFI in zebrafish is also demonstrated. Much broader application of CPy-Odots is also prospected after further surface functionalization. Given its simplicity, high fluorescence intensity, and wide availability of TADF materials, the method can be extended to develop more excellent TADF Odots for accomplishing the challenges in future bioimaging applications.
研究领域:
生物医学工程
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生物成像
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材料科学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2018
·
IF 4.37
Xin Jin,Qing Yang,Ning Cai
Introduction Ginsenoside compound K (CK) has effects on cell-cycle regulation, tumor growth inhibition, and apoptosis induction. However, it has limited applications in clinical settings because of its low solubility and poor absorption. Methods To overcome these limitations, we aimed to develop a mixed micellar system composed of phosphatidylcholine (PC) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine polyethylene glycol 2000 (DSPE PEG 2000; DP). CK encapsulated in PC/DP mixed micelles had enhanced solubility, permeability, and retention effects. Results Compared to free CK, the CK PC/DP micellar system exhibited improved anticancer effects in vitro, including cell-cycle arrest, apoptosis, and anti-invasion in human lung carcinoma A549 cells. The significant proapoptotic effect was reflected by increased chromosomal condensation, annexin V/propidium iodide staining, and related protein expression. In vitro cellular uptake and optical mouse imaging in vivo suggested that the improved antitumor effect was caused primarily by enhanced uptake and tumor targeting. Furthermore, an in vivo antitumor efficacy study indicated that the CK mixed micelles significantly inhibited tumor growth, thereby decreasing tumor volume at the end of the experiment as compared with that in the control mice. Histological analysis confirmed the antitumor effect with low toxicity. Conclusion The PC/DP micellar system was an effective drug delivery system for CK in tumor therapy.
研究领域:
药学
·
肿瘤学
·
药物递送系统
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DYES AND PIGMENTS
·
2024
·
IF 4.1
Zhijia Sheng,Chao Zhao,Xiaoyan Huang,Jing Wang,Yi Liu
Hypoxia is a common feature of solid tumors and is considered to be the fatal flaw of conventional photodynamic therapy (PDT), which severely reduces the overall therapeutic efficacy. Here, we developed a series of halogenated photosensitizers to address this issue. The results showed that the introduction of heavy atoms enhanced the spin-coupling effect of the photosensitizers and effectively improved the type I PDT (non-oxygen-dependent) efficiency. The preferred iodine-substituted photosensitizer NRh–I was used as the basic architecture, and further nitrosyl modification was performed to obtain the NO small-molecule prodrug, which was finally encapsulated with DSPE-mPEG 5k to obtain a biocompatible NO nanophotocontrolled prodrug. By using the enhanced permeability and retention effect (EPR), the prodrug system can precisely target the lesion site, release a high concentration of NO by photocontrol, kill the tumor cells, and at the same time, cascade with ROS released with the same “time-space” precision to generate higher cytotoxicity, ONOO − , which generates a stronger targeted synergistic therapeutic effect. This “butterfly effect” strategy maximizes the effect of PDT and broadens the idea of translational medicine.
研究领域:
癌症治疗
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药学
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生物医学工程
·
化疗
✓ 已验证
DOI
高影响因子
MOLECULAR PHARMACEUTICS
·
2024
·
IF 4.5
Jinmei Lai,Qunying Shi,Yongqi Xie,Yinyin Zhu,Shiyu Liang,Yi Chen,Jiali Yuan,Lihan Liu
Tumoral thermal defense mechanisms considerably attenuate the therapeutic outcomes of mild-temperature photothermal therapy (PTT). Thus, developing a simple, efficient, and universal therapeutic strategy to sensitize mild-temperature PTT is desirable. Herein, we report self-delivery nanomedicines ACy NPs comprising a near-infrared (NIR) photothermal agent (Cypate), mitochondrial oxidative phosphorylation inhibitor (ATO), and distearoylphosphatidylethanolamine-polyethylene glycol 2000 (DSPE–PEG2000), which have a high drug-loading efficiency that can reverse tumoral thermal resistance, thereby increasing mild-temperature PTT efficacy. ACy NPs achieved targeted tumor accumulation and performed NIR fluorescence imaging capability in vivo to guide tumor PTT for optimized therapeutic outcomes. The released ATO reduced intracellular ATP levels to downregulate multiple heat shock proteins (including HSP70 and HSP90) before PTT, which reversed the thermal resistance of tumor cells, contributing to the excellent results of mild-temperature PTT in vitro and in vivo. Therefore, this study provides a simple, biosafe, advanced, and universal heat shock protein-blocking strategy for tumor PTT.
研究领域:
纳米技术
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肿瘤学
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治疗诊断学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2022
·Vol. 14
·期 13
·5054-5067
·
IF 8.307
Beibei Zhang,Rui Xue,Chunyang Sun
Glioblastoma (GBM) is the most lethal primary intracranial tumor because of its high invasiveness and recurrence. Therefore, nanocarriers with blood–brain barrier (BBB) penetration and transcranial-controlled drug release and activation are rather attractive options for glioblastoma treatment. Herein, we designed a multifunctional nanocarrier (T-TKNPVP) that combined targeted X-ray-induced photodynamic therapy (X-PDT) and cascaded reactive oxygen species (ROS)-boosted chemotherapy. The T-TKNPVP loaded with verteporfin (VP) and paclitaxel (PTX) was self-assembled from an angiopep-2 (Ang) peptide, functionalized Ang-PEG-DSPE and ROS-sensitive PEG-TK-PTX conjugate. After systemic injection, the T-TKNPVP efficiently crossed the BBB and targeted the GBM cells via receptor-mediated transcytosis. Upon X-ray irradiation, they can generate a certain amount of ROS, which not only induces X-PDT but also locoregionally activates PTX release and action by cleaving the TK bridged bonds. As evidenced by 9.4 T MRI and other experiments, such nanocarriers offer significant growth inhibition of GBM in situ and prolong the survival times of U87-MG tumor-bearing mice. Taken together, the designed T-TKNPVP provided an alternative avenue for realizing transcranial X-PDT and X-ray-activated chemotherapy for targeted and locoregional GBM treatment in vivo.
研究领域:
癌症治疗
·
纳米技术
·
神经科学
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药学
·
放射学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2022
·
IF 6.51
Wenhao Gao,Jialiang Zhang,Weifeng Wang,Zhihong Liu,Mulan Chen,Xiaomu Hu,Lingjun Zeng,Changqing Zheng,Hongtao Song,Qian Zhang
Photodynamic therapy (PDT) shows very high potential for the clinical treatment of triple-negative breast cancer. However, the efficacy of PDT is significantly weakened by tumor hypoxia , the relatively high intracellular glutathione levels and the active proliferation of cancer cells. To address these issues, we developed a novel drug self-delivery nanorod (defined as AINRs) through the hydrophobic interaction among the mitochondrial complex III inhibitor (atovaquone, ATO), the photosensitizer (indocyanine green, ICG) and the dispersion stabilizer (distearoyl phosphoethanolamine-polyethylene glycol 2000, DSPE-PEG 2000). The AINRs showed a rod-like morphology with a mean diameter of 120.6 ± 5.4 nm , a zeta potential of −26.35 ± 1.63 mV and a significantly high drug loading rate of 93.48%. The results of in vitro cell experiments involving triple-negative breast cancer cell lines (4T1 cells and MDA-MB-231 cells) indicated that the AINRs could effectively block the oxidative phosphorylation of cancer cells through the inhibition of mitochondrial complex III, which results in the reduction of endogenous oxygen consumption and the decrease of the intracellular ATP level. The reduction of ATP content further inhibited the glutathione synthesis and arrested the cell cycle at the S-phase, which results in enhanced in vitro PDT efficacy of ICG. The results of in vivo antitumor activity in 4T1-bearing mice showed that the tumor growth inhibition rate of the AINRs with near-infrared laser irradiation (NIR) was greater than 90%, whereas the tumor growth inhibition rates of the AINRs without NIR, ICG with NIR and doxorubicin (3 mg/kg) were only 31.68%, 61.15% and 24.59%, respectively. In addition, the results of safety studies, including body weights, biochemical indicators and H&E staining images of the main organs demonstrated the security of the AINRs. In summary, this study showed that the oxidative phosphorylation inhibition of triple-negative breast cancer was a safe and effective method to enhance its PDT efficacy.
研究领域:
癌症治疗
·
纳米技术
·
药理学
·
细胞生物学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）