JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
Xuedi Zhang,Xue Zhao,Shanshan Tie,Haitao Wang,Mingqian Tan
Oil in water (O/W) nanocarriers were prepared for cellular enhanced astaxanthin delivery using a (3-carboxypropyl) triphenylphosphonium bromide (TPP)-modified casein by an ultrasonic self-emulsification method. The nanocarriers of casein emulsion loaded with astaxanthin and casein modified by TPP emulsion encapsulated with astaxanthin were 227 and 543 nm, respectively, with a spherical shape. The thermal stability and resistance to ultraviolet (UV) radiation ability of astaxanthin were significantly improved after encapsulation by the nanocarriers. The fluorescence colocalization imaging proved an accumulated effect of astaxanthin encapsulated in casein emulsion nanocarriers modified by TPP. Meanwhile, the astaxanthin loaded on TPP-modified nanocarriers could significantly protect the mitochondrial membrane potential from depolarization in the normal rat kidney (NRK) cells after oxidative damage. The cell viability assay demonstrated that the astaxanthin loaded on TPP-modified nanocarriers could enhance the growth of NRK and RAW264.7 cells as compared with astaxanthin encapsulated by casein emulsion without TPP modification.
研究领域:
纳米技术
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药学
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细胞生物学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2019
·
IF 9.518
Jiani Wang,Shupei Zhang,Hong Dai,Hongli Zheng,Zhensheng Hong,Yanyu Lin
A delicate dual-readout immunosensor based on tetraphenylporphyrin-polymer dots (TPP-Pdots) with brilliant photoelectrochemical and photothermal performance was first successfully fabricated for the ultrasensitive detection of sialic acid (SA). Herein, TPP-Pdots with good biocompatibility , extraordinary light-harvesting ability and excellent photothermal conversion efficiency was used to capture SA antibody as dual-functional bioprobe for generating photocurrent and temperature signal. Furthermore, the large surface and morphology-mediated of rutile-TiO 2 (R–TiO 2 ) was beneficial to load amounts of TPP-Pdots for improved PEC signal and photothermal signal. Importantly, the temperature readout resulted from the variation of target concentration could be easily obtained by a universal thermometer which was time-saving and cost-saving. Under the optimized experimental conditions, the photocurrent densities and temperature changes proportionally increased with the increasing of SA concentrations from 3.5 × 10 −5 ng/mL to 35 ng/mL (R = 0.996). Impressively, the dual-readout approach proposed here not only featured with good accuracy and high sensitivity for SA detection, but also paved the way for the development of a dual-readout immunoassay based on PEC biosensor.
研究领域:
分析化学
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生物传感器
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纳米技术
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生物医学工程
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2015
·Vol. 3
·期 36
·7291-7299
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IF 4.726
Yanfang Wang,Beibei Wang,Han Liao,Xiaojie Song,Hao Wu,Huihui Wang,Hujun Shen,Xiaojun Ma,Mingqian Tan
Mitochondrial dysfunctions cause numerous human disorders and the development of mitochondria-targeted nanocarriers for drug delivery has aroused great attention. Herein, we report the synthesis of a liposomal nanohybrid cerasome modified with triphosphonium (TPP) for drug delivery to the mitochondrial matrix. The cerasomes were observed to possess an average size of about 38 nm in diameter, and the theoretical simulation of GBEMP mapping demonstrated that the amphiphilic organotrialkoxysilanes were stable as a bilayer equilibrium conformation after self-assembly. The cerasomes showed good stability, excellent biocompatibility and sustainable drug release behavior. Moreover, the TPP-targeted cerasomes resulted in greater drug accumulation in mitochondria, thus leading to a greater antitumor effect as compared to non-targeted cerasomes by using doxorubicin as a modal drug. The specific accumulation of TPP-targeted cerasomes within mitochondria was also confirmed by using JC-1 as the fluorescent probe to analyze the mitochondrial transmembrane potential change.
研究领域:
药学
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纳米技术
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药物递送系统
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癌症研究
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产品关联
DOI
PubMed
高影响因子
Theranostics
·
2019
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IF 8.063
Hui Yu,Jia-Mi Li,Kai Deng,Wei Zhou,Cai-Xia Wang,Qian Wang,Kun-Heng Li,Hong-Yang Zhao,Shi-Wen Huang
The drug resistance in cancer treatment with DOX is mainly related to the overexpression of drug efflux proteins, residing in the plasma and nuclear membranes. Delivering DOX into the mitochondria, lacking drug efflux proteins, is an interesting method to overcome DOX resistance. To solve the problem of positively charged triphenylphosphonium (TPP) for mitochondrial targeting in vivo , a charge reversal strategy was developed. Methods: An acidity triggered cleavable polyanion PEI-DMMA (PD) was coated on the surface of positively charged lipid-polymer hybrid nanoparticle (DOX-PLGA/CPT) to form DOX-PLGA/CPT/PD via electrostatic interaction. The mitochondrial localization and anticancer efficacy of DOX-PLGA/CPT/PD was evaluated both in vitro and in vivo . Results: The surface negative charge of DOX-PLGA/CPT/PD prevents from rapid clearance in the blood and improved the accumulation in tumor tissue through the enhanced permeability and retention (EPR) effect. The hydrolysis of amide bonds in PD in weakly acidic tumor tissue leads to the conversion of DOX-PLGA/CPT/PD to DOX-PLGA/CPT. The positive charge of DOX-PLGA/CPT enhances the interaction with tumor cells, promotes the uptake and improves DOX contents in tumor cells. Once endocytosed by tumor cells, the exposed TPP in nanomedicine results in effective mitochondrial localization of DOX-PLGA/CPT. Afterward, DOX can release from the nanomedicine in the mitochondria, target mtDNA, induce tumor cells apoptosis and overcome DOX resistance of MCF-7/ADR breast cancer. Conclusion: Tumor acidity triggered charge reversal of TPP-containing nanomedicine and activation of mitochondrial targeting is a simple and effective strategy for the delivery of DOX into the mitochondria of cancer cells and overcoming DOX resistance of MCF-7/ADR tumor both in vitro and in vivo , providing new insight in the design of nanomedicines for cancer chemotherapy.
研究领域:
药剂学
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纳米技术
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肿瘤学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CHINESE JOURNAL OF POLYMER SCIENCE
·
2022
·Vol. 41
·期 4
·525-537
·
IF 3.815
Zhou Meng-Xue,Zhang Jia-Yu,Cai Xiao-Meng,Dou Rui,Ruan Li-Fo,Yang Wen-Jiang,Lin Wen-Chu,Chen Jun,Hu Yi
As one of the major challenges in tumor chemotherapy, multidrug resistance typically correlates with the poor drug penetration within tumor tissues and drug efflux by the ATP-driven efflux pumps in tumor cells. Herein, we design a kind of near-infrared (NIR) light- and acidity-activated micellar iPUTDN nanoparticle for mitochondria-targeting doxorubicin (DOX) delivery to combat DOX resistance in small-cell lung cancer. While the PEGylated iPUTDN nanoparticles can keep stealth in blood circulation, NIR irradiation at the tumor region can peel off the PEG shell from the nanoparticles, and the exposed iRGD can facilitate deep tumor penetration of the nanoparticles. After being internalized by DOX-resistant H69AR cells, the poly(β-aminoester)s (PAE)-based nanoparticles can release the triphenylphosphonium (TPP)-conjugated DOX (TDOX) into the cytosol, which can further accumulate in mitochondria with the aid of TPP. Consequently, the mitochondrial membrane potential and ATP content are both reduced in DOX-resistant H69AR cells. The in vivo therapeutic results show that TDOX-loaded nanoparticles with the aid of NIR light irradiation can effectively suppress the DOX-resistant small-cell lung cancer without noticeable adverse effects.
研究领域:
肿瘤学
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药学
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纳米技术
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癌症研究
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产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2020
·
IF 10.652
Bo Li,Qian Zhou,Haiyang Wang,Yongchao Zha,Peilian Zheng,Tong Yang,Dong Ma,Lin Qiu,Ximing Xu,Ye Hu,Anna Roig,Siming Yu,Wei Xue
Triple-negative breast cancer (TNBC) is a type of highly aggressive cancer that is hard to be cured by the commonly used chemotherapy, mainly due to the lack of effective tumor targeting ability of the current drugs and TNBC drug resistance. Therefore, development of novel strategies for precise and high-efficient therapy of TNBCs is urgently needed. In the present work, a multifunctional magnetic gold nanoheterostructure with photosensitizer Ce6 loading ( [email protected] ) was designed and synthesized for synergistic photothermal and photodynamic therapy (PTT/PDT) of TNBC. To improve the tumor targeting ability, cRGD and TPP cationic molecule, which can specifically target α v β 3 integrin of cancer cell membrane and mitochondria, respectively, were functionalized on the nanosystem obtaining [email protected] @RT. In vitro and in vivo fluorescent imaging demonstrated that cRGD and TPP functionalization largely enhanced the delivery-efficiency of [email protected] @RT into TNBC cells and tumors. Under 880 nm and 660 nm laser irradiations, [email protected] @RT exhibited strong hyperthermia effect and ROS generating ability, which exerted a synergistic anti-TNBC effect by completely suppressed the tumor growth of the nude mice model. Moreover, by integrating superparamagnetic and near infrared light absorption properties into a single nanocomposite , [email protected] @RT was proved to be able to realize magnetic resonance , X-ray computed tomography and photoacoustic tri-modal imaging of in vivo tumors. In all, we provide a novel strategy for precise delivery of functional nanosystems to TNBC tumors to achieve more satisfying treating outcome.
研究领域:
纳米技术
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癌症治疗
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医学成像
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材料科学
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产品关联
DOI
高影响因子
ChemNanoMat
·
2019
·Vol. 6
·期 1
·89-98
·
IF 3.431
Ming Gong,Jian Yang,Qixin Zhuang,Yongsheng Li,Jinlou Gu
Graphical A metal-organic framework (MOF)-based nanoplatform with dual-targeting functions toward cancer cells and their mitochondria is established, via a proposed phosphorylation modification strategy. With the complete coverage of targeting molecules (i. e., TPP molecules for mitochondrial targeting and FA molecules for tumoral targeting), the efficacy of photodynamic therapy is greatly improved. Due to the existence of hypoxic microenvironment, the efficacy of photodynamic therapy (PDT) is frequently weakened. As a result, targeted treatment toward oxygen-rich mitochondria is considered as a promising cancer therapy. Herein, both triphenylphosphine (TPP) and folic acid (FA) are simultaneously grafted onto nanoscale metal-organic frameworks (NMOFs) to realize dual-targeting delivery of the nanoplatforms into cancer cells and their mitochondria via the proposed phosphorylation modification strategy. A large amount of highly efficient photosensitizer of porphyrinic molecules is integrated into the NMOFs with a uniform particle size of about 65 nm. Thanks to the strong Zr−O−P bonding, a dense coverage of phosphonate-conjugating targeting molecules on NMOFs is obtained and each surficial unsaturated Zr−O cluster is adequately occupied. The resultant dual-targeting NMOFs feature high biostability and biocompatibility, as well as improved cellular uptake and mitochondrial accumulation. The PDT efficacy of these dual-targeting NMOFs is significantly improved with a low IC 50 of 0.74 μM upon 10 min light radiation, which is at least four times higher than that of non-targeting counterparts. This phosphorylation strategy would be hopeful for immobilizing a variety of biogenic groups on NMOFs to make them targetable to various specific organelles and to improve the therapy efficacy on related diseases.
研究领域:
癌症治疗
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纳米技术
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材料科学
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生物医学工程
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产品关联
DOI
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Wang Hongbo,Li Jing,Jin Jianbo,Hu Jingbo,Yang Chunlin
Oxidative stress plays a key role in the progress of acute lung injury (ALI), which is an acute, progressive respiratory failure characterized by alveolar capillary injury caused by various external and internal factors other than cardiogenic factors. Pulmonary vascular endothelial cells are the main target cells during ALI, and therefore the mitochondrial targeting antioxidant derivative triphenylphosphine-melatonin (TPP-MLT) was encapsulated in VCAM-1 antibodies-conjugated nanostructured lipid carriers (VCAM@TPP-MLT NLCs) for lung targeting delivery. VCAM@TPP-MLT NLCs could be preferentially internalized by inflammatory endothelial cells in lung tissues, and then the released TPP-MLT from NLCs effectively eliminated the excessive reactive oxide species (ROS) and ameliorated cell apoptosis. Overall, the results suggested that VCAM@TPP-MLT NLCs exhibited remarkable in vitro and in vivo therapeutic effect on ALI, and could be a promising and efficient strategy for the treatment of ALI.
研究领域:
药理学
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呼吸医学
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纳米技术
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2023
·
IF 15.1
Saijun Wang,Zaigang Zhou,Rui Hu,Mingyue Dong,Xiaobo Zhou,Siyan Ren,Yi Zhang,Chengxun Chen,Ruoyuan Huang,Man Zhu,Wanying Xie,Ling Han,Jianliang Shen,Congying Xie
At present, radiotherapy (RT) still acquires limited success in clinical due to the lessened DNA damage under hypoxia and acquired immune tolerance owing to the amplified programmed death ligand-1 (PD-L1) expression. Incredibly, intracellular PD-L1 expression depression is proven to better sensitize RT by inhibiting DNA damage repair. However, the disability of the clinically used antibodies in disrupting the extracellular PD-L1function still limits the effectiveness of radio-immunotherapy. Therefore, better PD-L1 regulation strategies are still urgently needed to better sensitize radio-immunotherapy. Hence, for this purpose, TPP-LND is synthesized by linking mitochondrial-targeted triphenylphosphine cations (TPP + ) to the antineoplastic agent lonidamine (LND), which significantly reduces the dose needed for LND to induce effective oxidative phosphorylation inhibition (2 vs 300 µ M ). Then, TPP-LND is wrapped with liposomes to form TPP-LND@Lip nanoparticles. By doing this, TPP-LND@Lip nanoparticles can sensitize RT by reversing the hypoxic microenvironment of tumors to generate more DNA damage and reducing the expression of PD-L1 via enhancing the adenosine 5′-monophosphate-activated protein kinase activation. As expected, these well-designed economical TPP-LND@Lip nanoparticles are more effective than conventional anti-PD-L1 antibodies to some extent.
研究领域:
肿瘤学
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药理学
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放射生物学
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免疫治疗
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Yu Shi,Wenzhen Bu,Dongchuan Chu,Wenzheng Lin,Ke Li,Xueping Huang,Xinglong Wang,Yin Wu,Shang Wu,Dandan Li,Zhuobin Xu,Zhipeng Cao,Hao Chen,Huihui Wang
Intervertebral disc degeneration (IVDD) is invariably accompanied by excessive accumulation of reactive oxygen species (ROS), resulting in progressive deterioration of mitochondrial function and senescence in nucleus pulposus cells (NPCs). Significantly, the main ROS production site in non-immune cells is mitochondria, suggesting mitochondria is a feasible therapeutic target to reverse IVDD. Triphenylphosphine (TPP), which is known as mitochondrial-tropic ligands, is utilized to modify carbon dot-supported Prussian blue (CD-PB) to scavenge superfluous intro-cellular ROS and maintain NPCs at normal redox levels. CD-PB-TPP can effectively escape from lysosomal phagocytosis, permitting efficient mitochondrial targeting. After strikingly lessening the ROS in mitochondria via exerting antioxidant enzyme-like activities, such as superoxide dismutase, and catalase, CD-PB-TPP rescues damaged mitochondrial function and NPCs from senescence, catabolism, and inflammatory reaction in vitro. Imaging evaluation and tissue morphology assessment in vivo suggest that disc height index, mean grey values of nucleus pulposus tissue, and histological morphology are significantly improved in the IVDD model after CD-PB-TPP is locally performed. In conclusion, this study demonstrates that ROS-induced mitochondrial dysfunction and senescence of NPCs leads to IVDD and the CD-PB-TPP possesses enormous potential to rescue this pathological process through efficient removal of ROS via targeting mitochondria, supplying a neoteric strategy for IVDD treatment.
研究领域:
生物医学工程
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组织工程
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骨科
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细胞生物学
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材料科学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Chuping Zheng,Fajiang Chen,Fangwen Yang,Zhan Li,Wei Yi,Gengjia Chen,Tianwang Li,Xiyong Yu,Xu Chen
Excess reactive oxide species (ROS) is a direct factor in myocardial injury death, thus anti-oxidant therapy is a necessary measure to prevent rapid death of cardiomyocyte cell. Cysteine (Cys) is a potent antioxidant but easily become instability because of the hyperactivity. Therefore, in order to protect the the stability of Cys, we according to the mitochondria are the main sites of ROS production, utilized the loading and ROS scavenging capacity of mesoporous polydopamine (mPDA) constructed a nanosystem targeting mitochondria with effectively ROS elimination capability by loading cysteine (Cys-mPDA@TPP). The mesoporous structure of mPDA effectively inhibited the advance reaction and hyperactivity of Cys, thus effectively improving its stability that reached the double-collaborative treatment excess ROS. In particular, Cys-mPDA@TPP achieved directly reacting with ROS in mitochondria under the targeting of triphenylphosphine (TPP), not only enhancing the elimination efficiency of ROS, but also preventing mitochondrial dysfunction of monocyte-macrophage. Furthermore, with double-collaborative ROS elimination, Cys-mPDA@TPP effectively prevent the damage of cardiomyocyte cell through inhibiting macrophage inflammatory response. Therefore, this study provides a new therapeutic strategy for myocardial inflammatory injury.
研究领域:
心脏病学
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纳米技术
·
药学
·
炎症研究
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产品关联
DOI
PubMed
高影响因子
FOOD HYDROCOLLOIDS
·
2024
·
IF 11
Shuangshuang Wang,Yi Ding,Liqing Xu,Jiaming Li,Minghui Zhang,Qisheng Hu,Haiyan Wang,Jiaying Zhang,Lili Zhao,Jing Zhang,Wupeng Ge
Anthocyanin (ACN), as a hydrophilic compound, has excellent antioxidant and anti-inflammatory biological activities, but its poor stability and low bioavailability limit widespread application in the food industry. In the current study, a novel nanocarrier based “one stone for multiple birds” response strategy was designed to enhance the in vitro bio-accessibility, targeting capabilities, and antioxidant activity of ACN. The forementioned strategy entailed the utilization of triphenylphosphonium bromide (TPP)-modified dual-natural milk-derived proteins (WPCA)-fucoidan (FD) conjugates as a wall material via an amide reaction. Subsequently, ACN-loaded nanocarriers were prepared by assembly assisted with ultrasound method through hydrogen bonding, ionic complexation, and hydrophobic interaction. Transmission electron microscopy revealed that the nanocarriers exhibited a sunflower-like shape with a size of around 936 nm (7 mg/mL of ACN). Exhilaratingly, a sunflower-like nanocarrier (SNC) achieved dual pH- and redox-responsive release in the presence of 10 mM of glutathione (GSH) at pH 7.4, exhibiting intestine-responsive release behavior, high bio-accessibility, environmental stability, colon-targeting safety. Meanwhile, the nanocarrier demonstrated superior targeting of mitochondria, as evidenced by a Pearson's correlation coefficient of 0.80 at 6 h. In vitro cell experiments showed that the ACN-loaded SNC significantly effectively suppressed the generation of ROS and mitochondrial depolarization caused by oxidative stress. These findings hold significant importance in the potential ability of the anthocyanin-loaded natural bioactive nanocarriers, particularly and can potentially mitigate exogenous oxidative stress effectively.
研究领域:
食品科学
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纳米技术
·
药学
·
生物技术
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产品关联
DOI
高影响因子