纳米药物递送系统的细胞药代动力学研究进展
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摘要
纳米药物递送系统(nano-DDS)具有缓控释、靶向等诸多优点,是新型药物递送系统研究的热点。传统宏观的药代动力学有时难以真实有效地预测体内药物的药效,迫切需要将传统的药代动力学研究拓展到细胞/亚细胞水平,进行细胞药代动力学研究。对nano-DDS细胞药代动力学的研究有助于更全面地阐明其在细胞中的作用机制,指导nano-DDS的设计与开发。本文主要总结了nano-DDS细胞药代动力学的研究内容和研究方法,为nano-DDS的前期设计提供重要的参考依据。
Nano-drug delivery systems(nano-DDS) are the hotspots of new drug delivery systems, which have many advantages, such as sustained and controlled release, targeting delivery. Traditional pharmacokinetics are difficult to predict the efficacy of drugs in vivo sometimes. It is urgently needed to extend the traditional pharmacokinetics studies to the cell/subcellular level and perform cell pharmacokinetic studies. The study on the pharmacokinetics of nano-DDS helps us to elucidate the mechanism of the actions of them in cells and guides us to design and develop nano-DDS more reasonably. This article summarizes the research content and methods on the cellular pharmacokinetics of nano-DDS, in order to provide an important reference for the early stage design of nano-DDS.
Nano-drug delivery systems(nano-DDS) are the hotspots of new drug delivery systems, which have many advantages, such as sustained and controlled release, targeting delivery. Traditional pharmacokinetics are difficult to predict the efficacy of drugs in vivo sometimes. It is urgently needed to extend the traditional pharmacokinetics studies to the cell/subcellular level and perform cell pharmacokinetic studies. The study on the pharmacokinetics of nano-DDS helps us to elucidate the mechanism of the actions of them in cells and guides us to design and develop nano-DDS more reasonably. This article summarizes the research content and methods on the cellular pharmacokinetics of nano-DDS, in order to provide an important reference for the early stage design of nano-DDS.
引文
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[29]Varshosaz J,Hassanzadeh F,Sadeghi-Aliabadi H,et al.Uptake of etoposide in CT-26 cells of colorectal cancer using folate targeted dextran stearate polymeric micelles[J].Biomed Res Int,2014,2014:708593.
[30]Xu P,Van Kirk EA,Zhan Y,et al.Targeted charge-reversal nanoparticles for nuclear drug delivery[J].Angew Chem Int Ed Engl,2007,46:4999-5002.
[31]Li Y,Xu X,Zhang X,et al.Tumor-specific multiple stimuliactivated dendrimeric nanoassemblies with metabolic blockade surmount chemotherapy resistance[J].ACS Nano,2016,11:416-429.
[32]Yin Q,Shen J,Zhang Z,et al.Reversal of multidrug resistance by stimuli-responsive drug delivery systems for therapy of tumor[J].Adv Drug Deliv Rev,2013,65:1699-1715.
[33]Wang J,Sun X,Mao W,et al.Tumor redox heterogeneityresponsive prodrug nanocapsules for cancer chemotherapy[J].Adv Mater,2013,25:3670-3676.
[34]Luo C,Sun J,Liu D,et al.Self-assembled redox dualresponsive prodrug-nanosystem formed by single thioetherbridged paclitaxel-fatty acid conjugate for cancer chemotherapy[J].Nano Lett,2016,16:5401-5408.
[35]Song Q,Wang X,Wang Y,et al.Reduction responsive selfassembled nanoparticles based on disulfide-linked drug-drug conjugate with high drug loading and antitumor efficacy[J].Mol Pharm,2016,13:190-201.
[36]Wang Y,Wang X,Deng F,et al.The effect of linkers on the self-assembling and anti-tumor efficacy of disulfide-linked doxorubicin drug-drug conjugate nanoparticles[J].J Control Release,2018,279:136-146.
[37]He B,Yang D,Qin M,et al.Increased cellular uptake of peptide-modified PEGylated gold nanoparticles[J].Biochem Biophys Res Commun,2017,494:339-345.
[38]Lu J,Chuan X,Zhang H,et al.Free paclitaxel loaded PEGylated-paclitaxel nanoparticles:preparation and comparison with other paclitaxel systems in vitro and in vivo[J].Int JPharm,2014,471:525-535.
[39]Zhou F,Feng B,Wang T,et al.Theranostic prodrug vesicles for reactive oxygen species-triggered ultrafast drug release and local-regional therapy of metastatic triple-negative breast cancer[J].Adv Funct Mater,2017.DOI:10.1002/adfm.201770272.
[40]Kedia N,Bagchi S.Time resolved FRET measurement in various heterogeneous media using merocyanine dye as a donor[J].Spectrochim Acta A Mol Biomol Spectrosc,2015,145:467-472.
[41]Deng F,Zhang H,Wang X,et al.Transmembrane pathways and mechanisms of rod-like paclitaxel nanocrystals through MDCK polarized monolayer[J].ACS Appl Mater Interfaces,2017,9:5803-5816.
[42]Li R,Song X,Zhang H,et al.The integrity study on PEG-PCLmicelles transcellular transported across MDCK epithelial cell monolayer using FRET technology[J].Acta Pharm Sin(药学学报),2016,51:1316-1324.
[43]Wang Y,Wang C,Li Y,et al.Digitization of endocytic pHby hybrid ultra-pH-sensitive nanoprobes at single-organelle resolution[J].Adv Mater,2017.DOI:10.1002/adma.201603794.
[44]Xie Y,Hu X,He H,et al.Tracking translocation of glucan microparticles targeting M cells:implications for oral drug delivery[J].J Mater Chem B,2016,4:2864-2873.
[45]Wang C,Wang Y,Li Y,et al.A nanobuffer reporter library for fine-scale imaging and perturbation of endocytic organelles[J].Nat Commun,2015,6:8524.
[46]Liang Y,Li S,Wang X,et al.A nanosystem of amphiphilic oligopeptide-drug conjugate actualizing bothαvβ3 targeting and reduction-triggered release for maytansinoid[J].Theranostics,2017,7:3306-3318.
[47]Shen F,Chu S,Bence AK,et al.Quantitation of doxorubicin uptake,efflux,and modulation of multidrug resistance(MDR)in MDR human cancer cells[J].J Pharmacol Exp Ther,2008,324:95-102.
[48]Shen F,Bailey BJ,Chu S,et al.Dynamic assessment of mitoxantrone resistance and modulation of multidrug resistance by valspodar(PSC833)in multidrug resistance human cancer cells[J].J Pharmacol Exp Ther,2009,330:423-429.
[49]Duvvuri M,Feng W,Mathis A,et al.A cell fractionation approach for the quantitative analysis of subcellular drug disposition[J].Pharm Res,2004,21:26-32.
[2]Lee WH,Loo CY,Young PM,et al.Recent advances in curcumin nanoformulation for cancer therapy[J].Expert Opin Drug Deliv,2014,11:1183-1201.
[3]Yang KY,Lin LC,Tseng TY,et al.Oral bioavailability of curcumin in rat and the herbal analysis from Curcuma longa by LC-MS/MS[J].J Chromatogr B,2007,853:183-189.
[4]Carcaboso AM,Elmeliegy MA,Shen J,et al.Tyrosine kinase inhibitor gefitinib enhances topotecan penetration of gliomas[J].Cancer Res,2010,70:4499-4508.
[5]Wang Y,Liu J,Zhang J,et al.A cell-based pharmacokinetics assay for evaluating tubulin-binding drugs[J].Int J Med Sci,2014,11:479-487.
[6]Zhou F,Zhang J,Li P,et al.Toward a new age of cellular pharmacokinetics in drug discovery[J].Drug Metab Rev,2011,43:335-345.
[7]Larsen AK,Escargueil AE,Skladanowski A.Resistance mechanisms associated with altered intracellular distribution of anticancer agents[J].Pharmacol Ther,2000,85:217-229.
[8]Duvvuri M,Krise JP.Intracellular drug sequestration events associated with the emergence of multidrug resistance:a mechanistic review[J].Front Biosci,2005,10:1499-1509.
[9]Wang J,Byrne JD,Napier ME,et al.More effective nanomedicines through particle design[J].Small,2011,7:1919-1931.
[10]Ni P,Zhang J,Liu J,et al.Research progress in cellular pharmacokinetics[J].Prog Pharm Sci(药学进展),2014,38:881-885.
[11]Dong J,Wang Y,Zhang J,et al.Multiple stimuli-responsive polymeric micelles for controlled release[J].Soft Matter,2012,9:370-373.
[12]Wang W,Cheng D,Gong F,et al.Design of multifunctional micelle for tumor-targeted intracellular drug release and fluorescent imaging[J].Adv Mater,2012,24:115-120.Pharm Sci,2005,94:1782-1793.
[13]Xiong X,Huang Y,Lu W,et al.Preparation of doxorubicinloaded stealth liposomes modified with RGD m mi etic and cellular association in vitro[J].Acta Pharm Sin(药学学报),2005,40:1085-1090.
[14]Mu CF,Balakrishnan P,Cui FD,et al.The effects of mixed MPEG-PLA/Pluronic copolymer micelles on the bioavailability and multidrug resistance of docetaxel[J].Biomaterials,2010,31:2371-2379.
[15]Kreuter J.Nanoparticles-a historical perspective[J].Int JPharm,2007,331:1-10.
[16]Duncan R,Sat YN.Tumor targeting by enhanced permeability and retention(EPR)effect[J].Ann Oncol,1998,9:39.
[17]Harushfrenkel O,Debotton N,Benita S,et al.Targeting of nanoparticles to the clathrin-mediated endocytic pathway[J].Biochem Biophys Res Commun,2007,353:26-32.
[18]Gratton SEA,Ropp PA,Pohlhaus PD,et al.The effect of particle design on cellular internalization pathways[J].Proc Natl Acad Sci U S A,2008,105:11613-11618.
[19]Paillard A,HindréF,Vignes-Colombeix C,et al.The importance of endo-lysosomal escape with lipid nanocapsules for drug subcellular bioavailability[J].Biomaterials,2010,31:7542-7554.
[20]Chithrani BD,Ghazani AA,Chan WC.Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells[J].Nano Lett,2006,6:662-668.
[21]Chithrani BD,Chan WC.Elucidating the mechanism of cellular uptake and removal of protein-coated gold nanoparticles of different sizes and shapes[J].Nano Lett,2007,7:1542-1550.
[22]Yu C,He B,Xiong MH,et al.The effect of hydrophilic and hydrophobic structure of amphiphilic polymeric micelles on their transport in epithelial MDCK cells[J].Biomaterials,2013,34:6284-6298.
[23]Chiu YL,Ho YC,Chen YM,et al.The characteristics,cellular uptake and intracellular trafficking of nanoparticles made of hydrophobically-modified chitosan[J].J Control Release,2010,146:152-159.
[24]Cartiera MS,Johnson KM,Rajendran V,et al.The uptake and intracellular fate of PLGA nanoparticles in epithelial cells[J].Biomaterials,2009,30:2790-2798.
[25]Zhang J,Liu J,Zhao Y,et al.Plasma and cellular pharmacokinetic considerations for the development and optimization of antitumor block copolymer micelles[J].Expert Opin Drug Deliv,2015,12:263-281.
[26]Xiong X,Huang Y,Lu W,et al.Intracellular delivery of doxorubicin with RGD-modified sterically stabilized liposomes for an improved antitumor efficacy:in vitro,and in vivo[J].J
[27]Wang J,Bhattacharyya J,Mastria E,et al.A quantitative study of the intracellular fate of pH-responsive doxorubicinpolypeptide nanoparticles[J].J Control Release,2017,260:100-110.
[28]Zheng N,Lian B,Du W,et al.Extraction protocol and liquid chromatography/tandem mass spectrometry method for determining micelle-entrapped paclitaxel at the cellular and subcellular levels:application to a cellular uptake and distribution study[J].J Chromatogr B,2018,1072:347-354.
[29]Varshosaz J,Hassanzadeh F,Sadeghi-Aliabadi H,et al.Uptake of etoposide in CT-26 cells of colorectal cancer using folate targeted dextran stearate polymeric micelles[J].Biomed Res Int,2014,2014:708593.
[30]Xu P,Van Kirk EA,Zhan Y,et al.Targeted charge-reversal nanoparticles for nuclear drug delivery[J].Angew Chem Int Ed Engl,2007,46:4999-5002.
[31]Li Y,Xu X,Zhang X,et al.Tumor-specific multiple stimuliactivated dendrimeric nanoassemblies with metabolic blockade surmount chemotherapy resistance[J].ACS Nano,2016,11:416-429.
[32]Yin Q,Shen J,Zhang Z,et al.Reversal of multidrug resistance by stimuli-responsive drug delivery systems for therapy of tumor[J].Adv Drug Deliv Rev,2013,65:1699-1715.
[33]Wang J,Sun X,Mao W,et al.Tumor redox heterogeneityresponsive prodrug nanocapsules for cancer chemotherapy[J].Adv Mater,2013,25:3670-3676.
[34]Luo C,Sun J,Liu D,et al.Self-assembled redox dualresponsive prodrug-nanosystem formed by single thioetherbridged paclitaxel-fatty acid conjugate for cancer chemotherapy[J].Nano Lett,2016,16:5401-5408.
[35]Song Q,Wang X,Wang Y,et al.Reduction responsive selfassembled nanoparticles based on disulfide-linked drug-drug conjugate with high drug loading and antitumor efficacy[J].Mol Pharm,2016,13:190-201.
[36]Wang Y,Wang X,Deng F,et al.The effect of linkers on the self-assembling and anti-tumor efficacy of disulfide-linked doxorubicin drug-drug conjugate nanoparticles[J].J Control Release,2018,279:136-146.
[37]He B,Yang D,Qin M,et al.Increased cellular uptake of peptide-modified PEGylated gold nanoparticles[J].Biochem Biophys Res Commun,2017,494:339-345.
[38]Lu J,Chuan X,Zhang H,et al.Free paclitaxel loaded PEGylated-paclitaxel nanoparticles:preparation and comparison with other paclitaxel systems in vitro and in vivo[J].Int JPharm,2014,471:525-535.
[39]Zhou F,Feng B,Wang T,et al.Theranostic prodrug vesicles for reactive oxygen species-triggered ultrafast drug release and local-regional therapy of metastatic triple-negative breast cancer[J].Adv Funct Mater,2017.DOI:10.1002/adfm.201770272.
[40]Kedia N,Bagchi S.Time resolved FRET measurement in various heterogeneous media using merocyanine dye as a donor[J].Spectrochim Acta A Mol Biomol Spectrosc,2015,145:467-472.
[41]Deng F,Zhang H,Wang X,et al.Transmembrane pathways and mechanisms of rod-like paclitaxel nanocrystals through MDCK polarized monolayer[J].ACS Appl Mater Interfaces,2017,9:5803-5816.
[42]Li R,Song X,Zhang H,et al.The integrity study on PEG-PCLmicelles transcellular transported across MDCK epithelial cell monolayer using FRET technology[J].Acta Pharm Sin(药学学报),2016,51:1316-1324.
[43]Wang Y,Wang C,Li Y,et al.Digitization of endocytic pHby hybrid ultra-pH-sensitive nanoprobes at single-organelle resolution[J].Adv Mater,2017.DOI:10.1002/adma.201603794.
[44]Xie Y,Hu X,He H,et al.Tracking translocation of glucan microparticles targeting M cells:implications for oral drug delivery[J].J Mater Chem B,2016,4:2864-2873.
[45]Wang C,Wang Y,Li Y,et al.A nanobuffer reporter library for fine-scale imaging and perturbation of endocytic organelles[J].Nat Commun,2015,6:8524.
[46]Liang Y,Li S,Wang X,et al.A nanosystem of amphiphilic oligopeptide-drug conjugate actualizing bothαvβ3 targeting and reduction-triggered release for maytansinoid[J].Theranostics,2017,7:3306-3318.
[47]Shen F,Chu S,Bence AK,et al.Quantitation of doxorubicin uptake,efflux,and modulation of multidrug resistance(MDR)in MDR human cancer cells[J].J Pharmacol Exp Ther,2008,324:95-102.
[48]Shen F,Bailey BJ,Chu S,et al.Dynamic assessment of mitoxantrone resistance and modulation of multidrug resistance by valspodar(PSC833)in multidrug resistance human cancer cells[J].J Pharmacol Exp Ther,2009,330:423-429.
[49]Duvvuri M,Feng W,Mathis A,et al.A cell fractionation approach for the quantitative analysis of subcellular drug disposition[J].Pharm Res,2004,21:26-32.