BIOMATERIALS
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2021
·
IF 12.479
Ruomeng Li,Xue Gong,Chen Hong,Hong Wang,Yingying Chen,Kaiyue Tan,Xiaoqing Liu,Fuan Wang
Extracellular vesicles (EVs) have been emerged as versatile drug delivery vehicles due to their outstanding biocompatibility and long-term circulation, yet are constrained with low targeting property and inefficient loading capacity from post-synthetic passive EVs encapsulation. Herein, we report a simple and feasible in situ biosynthetic approach to encapsulate tumor-targeting folate (FA)-modified EVs with intracellularly produced protoporphyrin X (PpIX) and doxorubicin (DOX). As compared with the traditional directly drug-incubated or drug-electroporated EVs, these biosynthesized EVs revealed high drug-loading efficiency with minimized structural and functional perturbations. Our multifunctional EVs revealed the enhanced accumulation and penetration into deep tumor parenchyma, as well as the strengthened immune response to ablate orthotopic and metastatic tumors, thus realizing the more reliable photochemotherapy. As an intelligent multi-mode therapeutic system, our biosynthetic EVs could be engineered with more therapeutic agents and show great promise for biomedicine applications.
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高影响因子
ACS Omega
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2021
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IF 3.512
Yun Wang,Min Gong,Zhuo Huang,Hai Min,Peng Yu,Fuzhou Tang,Yuannong Ye,Simian Zhu,Zuquan Hu,Zhu Zeng,Jin Chen
Hematoporphyrin (HP) and protoporphyrin IX (PPIX) are useful porphyrin photosensitizers with significant application values in photodynamic therapy. Currently, many strategies have been developed to improve their clinical performance, such as incorporating them with nanoparticle (NP) carriers. In this work, we studied the possibility of using β-lactoglobulin (BLG) as a potential NP carrier due to their hydrophobic affinity, pH sensitivity, and low cost of extraction and preservation. The interaction mechanisms of BLG with HP and PPIX were investigated using spectroscopic techniques and molecular docking methods. The molecular docking results agree well with the experimental results, which demonstrate that the formations of HP-BLG and PPIX-BLG complexes are endothermic processes and the main acting force is hydrophobic force. Furthermore, the opening–closure states of EF loop have a great influence on the HP-BLG complex formation, where the central hydrophobic cavity of β-barrel is available for HP binding at pH 7.4 but not available at pH 6.2. However, the formation of the PPIX-BLG complex is less dependent on the states of the EF loop, and the binding sites of PPIX are both located on the external surface of BLG under both pH 7.4 and 6.2 conditions. All of our results would provide new insight into the mechanisms of noncovalent interactions between BLG and HP/PPIX. It is believed that this work indicated the potential application values of BLG in designing pH-sensitive carriers for the delivery of HP and PPIX, as well as other poorly soluble drugs.
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ACS Applied Bio Materials
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2021
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IF 0
Chunmiao Yu,Yesheng Wang,Ruiping Wu,Zhentong Zhu,Bingling Li
As an important enzyme-free amplifier, the hybridization chain reaction (HCR) uses an ssDNA to trigger cycled displacement interactions between substrate hairpins and finally form elongated dsDNA concatamer mixtures. In many cases, to provide a signal probe or advanced function, additional oligonucleotides (named hairpin tails) have to be extended upon classic HCR hairpin substrates, but by doing so the HCR assembly efficiency and signal-to-noise ratio (SNR) may get seriously reduced. In this Article, a rational and general model that may guide the study on HCR functionalization and signaling efficiency is provided. We rationally design a four-hairpin model HCR system (4H-HCR) in which one or more hairpin substrates are appended with additional tails as a signaling probe. After HCR assembly, two adjacent tails are supposedly integrating into a full G-quadruplex structure to provide the evidence or signal for the assembly. A systematic study has been applied to reveal the relationship between the “tail-design” with assembly efficiency and SNR. A clear design rule-set guiding the optimized assembly and signal has been provided for traditional electrophoresis and G-quadruplex-enhanced fluorescence signal. Importantly, solid-state nanopore single molecular detection has been innovatively introduced and recommended as an “antirisk” and “mutual benefit” readout to traditional G-quadruplex signaling. Nanopore detection can provide a clear signal distinguished before and after the HCR reaction, especially when the traditional G-quadruplex-enhanced signal only provides low SNR. The G-quadruplex, in turn, may enhance the nanopore signal amplitude via increasing the diameter of the HCR products.
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Small
·
2021
·Vol. 17
·期 34
·2100753
·
IF 13.281
Ya-Xuan Zhu,Hao-Ran Jia,Yuxin Guo,Xiaoyang Liu,Ningxuan Zhou,Peidang Liu,Fu-Gen Wu
Tumor vasculature has long been considered as an extremely valuable therapeutic target for cancer therapy, but how to realize controlled and site-specific drug release in tumor blood vessels remains a huge challenge. Despite the widespread use of nanomaterials in constructing drug delivery systems, they are suboptimal in principle for meeting this demand due to their easy blood cell adsorption/internalization and short lifetime in the systemic circulation. Here, natural red blood cells (RBCs) are repurposed as a remote-controllable drug vehicle, which retains RBC's morphology and vessel-specific biodistribution pattern, by installing photoactivatable molecular triggers on the RBC membrane via covalent conjugation with a finely tuned modification density. The molecular triggers can burst the RBC vehicle under short and mild laser irradiation, leading to a complete and site-specific release of its payloads. This cell-based vehicle is generalized by loading different therapeutic agents including macromolecular thrombin, a blood clotting-inducing enzyme, and a small-molecule hypoxia-activatable chemodrug, tirapazamine. In vivo results demonstrate that the repurposed “anticancer RBCs” exhibit long-term stability in systemic circulation but, when tumors receive laser irradiation, precisely releases their cargoes in tumor vessels for thrombosis-induced starvation therapy and local deoxygenation-enhanced chemotherapy. This study proposes a general strategy for blood vessel-specific drug delivery.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2021
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IF 5.875
Xuerong Dong,Xiang Zhang,Manyuan Wang,Liwei Gu,Jing Li,Muxin Gong
Heme is a prosthetic group of hemoglobin comprising protoporphyrin IX (PPIX) with Fe 2+ . Studies have shown that modulating heme synthesis pathway in Plasmodium could greatly affect the action mechanism and antimalarial effect of artemisinin and its derivatives. Herein, an intraerythrocytic parasite targeted nanostructured lipid carrier (NLC) was developed for potentiation of artemether (ARM) by combination with PPIX and iron-loaded transferrin (holo-Tf). Firstly, ARM and PPIX were co-loaded into NLCs with high entrapment efficiency. Then, a targeting ligand heparin (HP) was electrostatically adsorbed onto the periphery of NLCs, followed by conjugation with holo-Tf to receive the final formulation Tf-HP-NLC/ARM/PPIX. Tf-HP-NLC/ARM/PPIX exhibited nanoscale particle size (~188 nm) and was relatively stable in simulated gastrointestinal fluids and rat plasma. A sustained drug release characteristic was observed in PBS (pH 7.4). In vitro targeting assay confirmed that Tf-HP-NLC/ARM/PPIX could be specifically and efficiently internalized into intraerythrocytic parasites via HP receptor-meditated endocytosis. Furthermore, due to enhanced intraparasitic accumulation and activated mechanism of ARM, the combinational delivery system Tf-HP-NLC/ARM/PPIX showed increased inhibitory activity against Plasmodium falciparum in culture and enhanced antimalarial effect in Plasmodium berghei -infected murine model, suggesting a promising strategy for development of new therapy based on action mechanism of ARM.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2021
·
IF 5.875
Congjun Xu,Haolan Yang,Zhanghong Xiao,Tao Zhang,Zilin Guan,Jie Chen,Hualu Lai,Xiaoyu Xu,Yanjuan Huang,Zeqian Huang,Chunshun Zhao
The pentose phosphate pathway (PPP) plays a critical role by providing ribulose-5-phosphate (Ru5P) and NADPH for nucleotide synthesis and reduction energy, respectively. Accordingly, blocking the PPP process may be an effective strategy for enhancing oxidation therapy and inhibiting cell replication. Here, we designed a novel reduction-responsive PEGylated prodrug and constructed nanoparticles [email protected] to simultaneously deliver a PPP blocker, dehydroepiandrosterone (DHEA), and chemotherapeutic camptothecin (CPT) to integrate amplification of oxidation therapy and enhance cell replication inhibition. Following cellular uptake, DHEA and CPT were released from [email protected] in the presence of high glutathione (GSH) levels. As expected, DHEA-mediated reduction level decreases and CPT-induced oxidation level increases synergistically, breaking the redox balance to aggravate cancer oxidative stress. In addition, suppressing nucleotide synthesis by DHEA through the reduction of Ru5P and blocking DNA replication by CPT further motivates a synergistic inhibition effect on tumor cell proliferation . The results showed that [email protected] featuring multimodal treatment has satisfactory antitumor activity both in vitro and in vivo . This study provides a new tumor treatment strategy, which combines the amplification of oxidative stress and enhancement of inhibition of cell proliferation based on inhibition of the PPP process.
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高影响因子
ACS Catalysis
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2021
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IF 13.084
Yiyang Lin,Kang Liu,Kejun Chen,Yan Xu,Hongmei Li,Junhua Hu,Ying-Rui Lu,Ting-Shan Chan,Xiaoqing Qiu,Junwei Fu,Min Liu
Atomically dispersed FeN4 catalysts have been considered as potential materials to replace Pt-based catalysts for the oxygen reduction reaction (ORR), but they often suffer from sluggish O2 activation kinetics due to the symmetrical charge distribution. Herein, we introduce external N, including pyrrolic-N (PN) and graphitic-N (GN), as an electron acceptor near FeN4 to regulate its charge distribution and improve its ORR activity. Theoretical calculations reveal that introduction of PN evokes much enhanced electron redistribution and local electrical field on the Fe site compared with those observed with GN introduction and the pristine one. Synchrotron X-ray absorption spectroscopy and X-ray photoelectron spectroscopy validate the positive charge accumulation of Fe in the FeN4 site induced by introducing PN. Thus, the obtained FeN4-PN exhibits a great performance for ORR in 0.1 M KOH with a remarkable half-wave potential of 0.91 V versus reversible hydrogen electrode, as well as a Tafel slope of 58 mV decade–1. This work provides a guide to improve the catalytic performances of single-atom catalysts by introducing charge-redistribution sites.
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Journal of Materials Chemistry B
·
2021
·Vol. 9
·期 37
·7686-7697
·
IF 6.331
Jingmei Guo,Yue Xu,Miaodeng Liu,Jian Yu,Hongye Yang,Wenlong Lei,Cui Huang
The validity and biocompatibility of irrigating agents are imperative for the success of root canal therapy. The imperfections in the currently available irrigants highlight the fact that more advanced technologies and strategies are required for complete disinfection in endodontic treatments. In the present study, a Fenton reaction-enhanced antimicrobial sonodynamic therapy (SDT) platform was fabricated for root canal disinfection. Firstly, mesoporous silica nanoparticles (MSNs) were synthesized, grafted with an amino group and then conjugated with sonosensitizer protoporphyrin IX (PpIX). Iron ions were then anchored (M@P-Fe) to initiate a Fenton reaction. Nanoparticle characterization by size and zeta potential measurements, scanning electron microscopy, transmission electron microscopy and thermogravimetric analysis confirmed that the platform was successfully developed. Reactive oxygen species (ROS) generation assessment, methylene blue degradation and electron spin resonance assays illustrated upon ultrasound (US) irradiation, that augmented ROS, can be produced by US activated PpIX and iron mediated Fenton reactions from low concentration H2O2 (0.01%). In vitro anti-Enterococcus faecalis efficacy was demonstrated by growth curve and colony forming unit measurements. Confocal laser scanning microscopy and scanning electron microscopy observations illustrated the effectiveness of the platform on in situ biofilm eradication in root canal. Owing to the stronger oxidizing capability and short lifetime of ROS, the Fenton reaction-enhanced SDT can induce detrimental oxidative damage to bacteria upon activation of US while avoiding nonspecific toxicity to cells, which was verified by cytotoxicity evaluations using CCK-8 assay and morphology observation of MC3T3-E1 cells. Compared to commonly used NaClO, this nanoplatform displayed desirable anti-bacterial, anti-biofilm abilities and better biocompatibility. These results highlight that the integrated M@P-Fe + US + H2O2 platform is a promising candidate for US enhanced root canal irrigation and disinfection.
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高影响因子
MICROCHIMICA ACTA
·
2021
·Vol. 188
·期 3
·1-9
·
IF 5.833
Zhu Jing,Liu Xia,Zheng Jinxue,Jiang Dafeng
A dual channel method is described for the determination of the amyloid-β peptide Aβ(1–40) that is associated with Alzheimer’s disease. The method exploits (a) conformational changes of a G-quadruplex that are triggered by Na + and K + ions and (b) the strong affinity between Aβ(1–40) and Cu 2+ . A G-quadruplex DNA forms an antiparallel structure in the presence of Na + and can catalyze the oxidation of tetramethylbenzidine by H 2 O 2 system in the presence of Cu 2+ to form a visible blue color. If, however, Cu 2+ binds to Aβ(1–40), the blue color is no longer formed. Measuring the absorption decrease at 452 nm, the determination of Aβ(1–40) is realized. If K + is added to the Na + -containing buffer, the antiparallel G-quadruplex DNA is transformed to parallel. This leads to the insertion of protoporphyrin IX (PPIX) into the G-quadruplex and generates enhanced fluorescent signal, with excitation/emission wavelength at 410/630 nm. The G-quadruplex then catalyzes the metalation of PPIX by Cu 2+ , and the fluorescence intensity decreases. In the presence of Aβ(1–40), the formation of Aβ(1–40)-Cu 2+ triggers the recovery of the fluorescence. The Na + /K + -induced tuning of the conformation of the G-quadruplex with the same sequence enables dual (colorimetric and fluorometric) determination of Aβ(1–40), with detection limits of 4.9 pM and 2.3 pM, respectively. The cost is quite low since the developed strategy is label free and enzyme free by using low-cost DNA and Cu 2+ . More importantly, the dual channel determination operation is very simple without any further modification process. Graphical abstract
Tuning the conformation of G-quadruplexes by sodium(I) and potassium(I): application to photometric and fluorometric determination of amyloid β(1–40).
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JOURNAL OF RAMAN SPECTROSCOPY
·
2020
·Vol. 51
·期 12
·2447-2457
·
IF 2
Kainan Zhang,Xinjie Cai,Yaru Guo,Chuanzi Liu,Tao Jiang,Yining Wang
Changes in mineral content (mainly phosphate) are important for detecting primary dental caries. However, so far, there has not been a device that can provide detailed information on the changes in organic and inorganic content of dental caries during the caries development and sensitively found early dental caries. DIAGNOdent has been widely used as a laser device for detecting dental caries, but it does not provide information about dental inorganics. Our experiment synthesised hydroxyapatite-aromatic amino acids (HA-AAAs), protoporphyrin IX (HA-PPIX), and tetracycline hydrochloride (HA-TCN) complexes as a simple biological mineralization model related to teeth in vitro and achieved single-factor control to avoid impurity interference so that the test results are accurate. For the first time, Raman and DIAGNOdent were used to detect HA-AAAs, HA-PPIX, and HA-TCN and determine the fluorescence characteristics of each organic substance. Our results show that Raman results are consistent with DIAGNOdent readings when detecting complexes and that Raman relative intensity (RRI) calculated by Raman spectroscopy can directly reflect the phosphate content in the sample. This implies that Raman is possible to replace DIAGNOdent as a novel and more accurate caries detector after conversion of the spectrum results.
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ACS Nano
·
2020
·
IF 14.588
Bin Qiao,Yuanli Luo,Hong-Bo Cheng,Jianli Ren,Jin Cao,Chao Yang,Bing Liang,Anyu Yang,Xun Yuan,Jinrui Li,Liming Deng,Pan Li,Hai-Tao Ran,Lan Hao,Zhiyi Zhou,Maoping Li,Yuanyuan Zhang,Peter S. Timashev,Xing-Jie Liang,Zhigang Wang
Organic–inorganic hybrid materials have drawn increasing attention as photothermal agents in tumor therapy due to the advantages of green synthesis, high loading efficiency of hydrophobic drugs, facile incorporation of theranostic iron, and excellent photothermal efficiency without inert components or additives. Herein, we proposed a strategy for biomimetic engineering-mediated enhancement of photothermal performance in the tumor microenvironment (TME). This strategy is based on the specific characteristics of organic–inorganic hybrid materials and endows these materials with homologous targeting ability and photothermal stability in the TME. The hybrid materials perform the functions of cancer cells to target homolytic tumors (acting as “artificial nanotargeted cells (ANTC)”). Inspired by the pH-dependent disassembly behaviors of tannic acid (TA) and ferric ion (FeIII) and subsequent attenuation of photothermal performance, cancer cell membranes were self-deposited onto the surfaces of protoporphyrin-encapsulated TA and FeIII nanoparticles to achieve ANTC with TME-stable photothermal performance and tumor-specific phototherapy. The resulting ANTC can be used as contrast agents for concurrent photoacoustic imaging, magnetic resonance imaging, and photothermal imaging to guide the treatment. Importantly, the high loading efficiency of protoporphyrin enables the initiation of photodynamic therapy to enhance photothermal therapeutic efficiency, providing antitumor function with minimal side effects.
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高影响因子
Frontiers in Pharmacology
·
2020
·
IF 4.225
Lv Jinpeng,An Xiaohong,Jiang Songzhou,Yang Ying,Song Guoqiang,Gao Rongyin
Protoporphyrin IX (PPIX) is a heterocyclic organic compound that is the last intermediate in the heme biosynthetic pathway. PPIX, due to its photodynamic effects, is utilized in the treatment of skin diseases. Furthermore, PPIX has been utilized as a melanogenesis-stimulating agent in various studies. However, the exact function and mechanism underlying PPIX action in melanocytes remain to be elucidated. In the present study, we sought to further investigate how PPIX affects melanocyte melanogenesis, and whether PPIX is involved in melanin transport. Our findings demonstrated that PPIX increased melanocyte dendricity and melanosome transport, in addition to increasing melanogenesis. PPIX functions primarily by activating the guanylate cyclase (GC) and cyclic guanosine 3’, 5’-monophosphate/protein kinase G (cGMP/PKG) signaling pathways. Once activated, these pathways increase tyrosinase activity and the expression of microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 and -2 (TRP-1 and TRP-2), myosin Va, melanophinin, Ras-related protein Rab-27A (Rab27a), and cell division cycle 42 (Cdc42), promoting melanogenesis, melanocyte dendricity, and melanosome transport. Furthermore, the melanogenic effects of PPIX were confirmed in vivo in a zebrafish model system. Our results indicate that PPIX is not cytotoxic and may, thus, be utilized as a pigmentation enhancer.
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高影响因子
危险品化学品经营许可证（带存储）