Recent Advances in Molecular Imaging of Atherosclerotic Plaque

doi:10.7517/issn.1674-0475.181102

Abstract

Abstract: Atherosclerosis-related cardiovascular diseases (e.g., acute myocardial infarction and stroke) are the leading causes of morbidity and mortality in the world today. The rupture of atherosclerotic plaques is the main pathological basis of acute cardiovascular disease events with no obvious clinical symptoms in the early stage of atherosclerosis. How to accurately identify vulnerable plaques and effective treatments in patients before acute cardiovascular and cerebrovascular events has become an urgent problem to solve, it is also the key to reduce the incidence of acute cardiovascular events. The rapid development of non-invasive molecular imaging technology in recent years has brought new opportunities for the diagnosis and treatment of atherosclerotic plaque.

Key words: atherosclerosis plaque, molecular imaging, molecular probe, nanomaterials

MU Yalin, CHEN Xiaomei, LIU Xuan, LIU Gang. Recent Advances in Molecular Imaging of Atherosclerotic Plaque[J]. Imaging Science and Photochemistry, 2019, 37(1): 7-17.

References

[1] Campbell L A,Rosenfeld M E. Infection and atherosclerosis development[J]. Archives of Medical Research, 2015, 46(5):339-350.
[2] Lusis A J. Atherosclerosis[J]. Nature, 2000, 407(6801):233-241.
[3] Sanz J,Fayad Z A. Imaging of atherosclerotic cardiovascular disease[J]. Nature, 2008, 451(7181):953-957.
[4] Mulder W J, Jaffer F A, Fayad Z A,Nahrendorf M. Imaging and nanomedicine in inflammatory atherosclerosis[J]. Science Translational Medicine, 2014, 6(239):239sr231.
[5] Libby P, Ridker P M,Hansson G K. Progress and challenges in translating the biology of atherosclerosis[J]. Nature, 2011, 473(7347):317-325.
[6] Lu H,Daugherty A. Atherosclerosis[J]. Arteriosclerosis, Thrombosis, and Vascular Biology, 2015, 35(3):485-491.
[7] Moore K J, Sheedy F J,Fisher E A. Macrophages in atherosclerosis:a dynamic balance[J]. Nature Reviews Immunology, 2013, 13(10):709-721.
[8] Weber C,Noels H. Atherosclerosis:current pathogenesis and therapeutic options[J]. Nature Medicine, 2011, 17(11):1410-1422.
[9] Kalz J, Cate H T, Spronk H M. Thrombin generation and atherosclerosis[J]. Journal of Thrombosis and Thrombolysis, 2014, 37(1):45-55.
[10] Hsiai T K, Cho S K, Wong P K, Ing M, Salazar A, Sevanian A, Navab M, Demer L L, Ho C M. Monocyte recruitment to endothelial cells in response to oscillatory shear stress[J]. Faseb Journal, 2003, 17(12):1648-1657.
[11] Mlinar L B, Chung E J, Wonder E A,Tirrell M. Active targeting of early and mid-stage atherosclerotic plaques using self-assembled peptide amphiphile micelles[J]. Biomaterials, 2014, 35(30):8678-8686.
[12] Ludewig B,Laman J D. The in and out of monocytes in atherosclerotic plaques:balancing inflammation through migration[J]. Proceedings of the National Academy of Sciences of the United States of America, 2004, 101(32):11529-11530.
[13] Moore K J,Freeman M W. Scavenger receptors in atherosclerosis:beyond lipid uptake[J]. Arteriosclerosis, Thrombosis, and Vascular Biology, 2006, 26(8):1702-1711.
[14] Chan J M, Zhang L F, Tong R, Ghosh D, Gao W W, Liao G, Yuet K P, Gray D, Rhee J W, Cheng J J, Golomb G, Libby P, Langer R,Farokhzad O C. Spatiotemporal controlled delivery of nanoparticles to injured vasculature[J]. Proceedings of the National Academy of Sciences of the United States of America, 2010, 107(5):2213-2218.
[15] Adiguzel E, Ahmad P J, Franco C,Bendeck M P. Collagens in the progression and complications of atherosclerosis[J]. Vascular Medicine, 2009, 14(1):73-89.
[16] Chen W, Cormode D P, Vengrenyuk Y, Herranz B, Feig J E, Klink A, Mulder W J, Fisher E A,Fayad Z A. Collagen-specific peptide conjugated hdl nanoparticles as MRI contrast agent to evaluate compositional changes in atherosclerotic plaque regression[J].JACC Cardiovasc Imaging, 2013, 6(3):373-384.
[17] Pan H, Myerson J W, Hu L, Marsh J N, Hou K, Scott M J, Allen J S, Hu G, San Roman S, Lanza G M, Schreiber R D, Schlesinger P H,Wickline S A. Programmable nanoparticle functionalization for in vivo targeting[J]. Faseb Journal, 2013, 27(1):255-264.
[18] Nahrendorf M, Jaffer F A, Kelly K A, Sosnovik D E, Aikawa E, Libby P,Weissleder R. Noninvasive vascular cell adhesion molecule-1 imaging identifies inflammatory activation of cells in atherosclerosis[J]. Circulation, 2006, 114(14):1504-1511.
[19] Calin M, Stan D, Schlesinger M, Simion V, Deleanu M, Constantinescu C A, Gan A M, Pirvulescu M M, Butoi E, Manduteanu I, Bota M, Enachescu M, Borsig L, Bendas G,Simionescu M. VCAM-1 directed target-sensitive liposomes carrying CCR2 antagonists bind to activated endothelium and reduce adhesion and transmigration of monocytes[J]. European Journal of Pharmaceutics and Biopharmaceutics, 2015, 89:18-29.
[20] Kelly K A, Allport J R, Tsourkas A, Shinde-Patil V R, Josephson L,Weissleder R. Detection of vascular adhesion molecule-1 expression using a novel multimodal nanoparticle[J]. Circulation Research, 2005, 96(3):327-336.
[21] Park K, Hong H Y, Moon H J, Lee B H, Kim I S, Kwon I C,Rhee K. A new atherosclerotic lesion probe based on hydrophobically modified chitosan nanoparticles functionalized by the atherosclerotic plaque targeted peptides[J]. Journal of Controlled Release, 2008, 128(3):217-223.
[22] Winter P M, Caruthers S D, Zhang H, Williams T A, Wickline S A,Lanza G M. Antiangiogenic synergism of integrin-targeted fumagillin nanoparticles and atorvastatin in atherosclerosis[J].JACC Cardiovascular Imaging, 2008, 1(5):624-634.
[23] Wang Y B, Chen J W, Yang B, Qiao H Y, Gao L, Su T, Ma S, Zhang X T, Li X J, Liu G, Cao J B, Chen X Y, Chen Y D,Cao F. In vivo MR and fluorescence dual-modality imaging of atherosclerosis characteristics in mice using profilin-1 targeted magnetic nanoparticles[J]. Theranostics, 2016, 6(2):272-286.
[24] Gao W, Sun Y H, Cai M, Zhao Y J, Cao W H, Liu Z H, Cui G W,Tang B. Copper sulfide nanoparticles as a photothermal switch for TRPV1 signaling to attenuate atherosclerosis[J]. Nature Communications, 2018, 9(1):231.
[25] Lowell A N, Qiao H, Liu T, Ishikawa T, Zhang H, Oriana S, Wang M, Ricciotti E, Fitzgerald G A, Zhou R,Yamakoshi Y. Functionalized low-density lipoprotein nanoparticles for in vivo enhancement of atherosclerosis on magnetic resonance images[J]. Bioconjugate Chemistry, 2012, 23(11):2313-2319.
[26] Zhao Y, Black A S, Bonnet D J, Maryanoff B E, Curtiss L K, Leman L J,Ghadiri M R. In vivo efficacy of HDL-like nanolipid particles containing multivalent peptide mimetics of apolipoprotein A-I[J]. Journal of Lipid Research, 2014, 55(10):2053-2063.
[27] Cormode D P, Briley-Saebo K C, Mulder W J, Aguinaldo J G, Barazza A, Ma Y, Fisher E A,Fayad Z A. An ApoA-I mimetic peptide high-density-lipoprotein-based MRI contrast agent for atherosclerotic plaque composition detection[J]. Small, 2008, 4(9):1437-1444.
[28] Sanchez-Gaytan B L, Fay F, Lobatto M E, Tang J, Ouimet M, Kim Y, Van Der Staay S E, Van Rijs S M, Priem B, Zhang L, Fisher E A, Moore K J, Langer R, Fayad Z A,Mulder W J. HDL-mimetic PLGA nanoparticle to target atherosclerosis plaque macrophages[J]. Bioconjugate Chemistry, 2015, 26(3):443-451.
[29] Perez-Medina C, Binderup T, Lobatto M E, Tang J, Calcagno C, Giesen L, Wessel C H, Witjes J, Ishino S, Baxter S, Zhao Y, Ramachandran S, Eldib M, Sanchez-Gaytan B L, Robson P M, Bini J, Granada J F, Fish K M, Stroes E S, Duivenvoorden R, Tsimikas S, Lewis J S, Reiner T, Fuster V, Kjaer A, Fisher E A, Fayad Z A,Mulder W J. In vivo PET imaging of HDL in multiple atherosclerosis models[J]. JACC Cardiovascular Imaging, 2016, 9(8):950-961.
[30] Tang J, Baxter S, Menon A, Alaarg A, Sanchez-Gaytan B L, Fay F, Zhao Y, Ouimet M, Braza M S, Longo V A, Abdel-Atti D, Duivenvoorden R, Calcagno C, Storm G, Tsimikas S, Moore K J, Swirski F K, Nahrendorf M, Fisher E A, Perez-Medina C, Fayad Z A, Reiner T,Mulder W J. Immune cell screening of a nanoparticle library improves atherosclerosis therapy[J]. Proceedings of the National Academy of Sciences of the United States of America, 2016, 113(44):E6731-E6740.
[31] Hyafil F, Cornily J C, Feig J E, Gordon R, Vucic E, Amirbekian V, Fisher E A, Fuster V, Feldman L J,Fayad Z A. Noninvasive detection of macrophages using a nanoparticulate contrast agent for computed tomography[J]. Nature Medicine, 2007, 13(5):636-641.
[32] Luehmann H P, Detering L, Fors B P, Pressly E D, Woodard P K, Randolph G J, Gropler R J, Hawker C J,Liu Y.PET/CT imaging of chemokine receptors in inflammatory atherosclerosis using targeted nanoparticles[J]. The Journal of Nuclear Medicine, 2016, 57(7):1124-1129.
[33] Bagalkot V, Badgeley M A, Kampfrath T, Deiuliis J A, Rajagopalan S,Maiseyeu A. Hybrid nanoparticles improve targeting to inflammatory macrophages through phagocytic signals[J]. Journal of Controlled Release, 2015, 217:243-255.
[34] Qiao R R, Qiao H Y, Zhang Y, Wang Y B, Chi C W, Tian J, Zhang L F, Cao F,Gao M Y. Molecular imaging of vulnerable atherosclerotic plaques in vivo with osteopontin-specific upconversion nanoprobes[J]. American Chemical Society Nano, 2017, 11(2):1816-1825.
[35] Hamzah J, Kotamraju V R, Seo J W, Agemy L, Fogal V, Mahakian L M, Peters D, Roth L, Gagnon M K, Ferrara K W,Ruoslahti E. Specific penetration and accumulation of a homing peptide within atherosclerotic plaques of apolipoprotein E-deficient mice[J].Proceedings of the National Academy of Sciences of the United States of America, 2011, 108(17):7154-7159.
[36] Kim M H, Kim B, Lim E K, Choi Y, Choi J, Kim E, Jang E, Park H S, Suh J S, Huh Y M,Haam S. Magnetic nanoclusters engineered by polymer-controlled self-assembly for the accurate diagnosis of atherosclerotic plaques via magnetic resonance imaging[J]. Macromolecular Bioscience, 2014, 14(7):943-952.
[37] Beldman T J, Senders M L, Alaarg A, Perez-Medina C,Tang J. Hyaluronan nanoparticles selectively target plaque-associated macrophages and improve plaque stability in atherosclerosis[J]. American Chemical Society Nano, 2017, 11(6):5785-5799.
[38] Chung E J, Mlinar L B, Nord K, Sugimoto M J, Wonder E, Alenghat F J, Fang Y,Tirrell M. Monocyte-targeting supramolecular micellar assemblies:a molecular diagnostic tool for atherosclerosis[J]. Advanced Healthcare Materials, 2015, 4(3):367-376.
[39] Jacobin-Valat M J, Laroche-Traineau J, Lariviere M, Mornet S, Sanchez S, Biran M, Lebaron C, Boudon J, Lacomme S, Cerutti M,Clofent-Sanchez G. Nanoparticles functionalised with an anti-platelet human antibody for in vivo detection of atherosclerotic plaque by magnetic resonance imaging[J]. Nanomedicine, 2015, 11(4):927-937.
[40] Kamaly N, Fredman G, Fojas J J, Subramanian M, Choi W I, Zepeda K, Vilos C, Yu M, Gadde S, Wu J, Milton J, Carvalho Leitao R, Rosa Fernandes L, Hasan M, Gao H, Nguyen V, Harris J, Tabas I,Farokhzad O C. Targeted interleukin-10 nanotherapeutics developed with a microfluidic chip enhance resolution of inflammation in advanced atherosclerosis[J]. American Chemical Society Nano, 2016, 10(5):5280-5292.
[41] Sinha A, Shaporev A, Nosoudi N, Lei Y, Vertegel A, Lessner S,Vyavahare N. Nanoparticle targeting to diseased vasculature for imaging and therapy[J]. Nanomedicine, 2014, 10(5):1003-1012.
[42] Yoo S P, Pineda F, Barrett J C, Poon C, Tirrell M,Chung E J. Gadolinium-functionalized peptide amphiphile micelles for multimodal imaging of atherosclerotic lesions[J].American Chemical Society Omega, 2016, 1(5):996-1003.
[43] Wen S, Liu D F, Liu Z, Harris S, Yao Y Y, Ding Q, Nie F, Lu T, Chen H J, An Y L, Zang F C,Teng G J. OxLDL-targeted iron oxide nanoparticles for in vivo MRI detection of perivascular carotid collar induced atherosclerotic lesions in ApoE-deficient mice[J]. Journal of Lipid Research, 2012, 53(5):829-838.
[44] Godin B, Sakamoto J H, Serda R E, Grattoni A, Bouamrani A,Ferrari M. Emerging applications of nanomedicine for the diagnosis and treatment of cardiovascular diseases[J]. Trends in Pharmacological Sciences, 2010, 31(5):199-205.
[45] Zeng Y, Zhu J, Wang J Q, Parasuraman P, Busi S, Nauli S M, Wang Y X J, Pala R,Liu G. Functional probes for cardiovascular molecular imaging[J]. Quantitative Imaging in Medicine and Surgery, 2018, 8(8):838-852.
[46] Kim B Y, Rutka J T,Chan W C. Nanomedicine[J]. The New England Journal of Medicine, 2010, 363(25):2434-2443.
[47] Li L, Wang J Q, Kong H R, Zeng Y,Liu G. Functional biomimetic nanoparticles for drug delivery and theranostic applications in cancer treatment[J]. Science and Technology of Advanced Materials, 2018, 19(1):771-790.
[48] Nguyen L T H, Muktabar A, Tang J, Dravid V P, Thaxton C S, Venkatraman S,Ng K W. Engineered nanoparticles for the detection, treatment and prevention of atherosclerosis:How close are we?[J].Drug Discovery Today, 2017, 22(9):1438-1446.
[49] Mishra S, Bedja D, Amuzie C, Foss C A, Pomper M G, Bhattacharya R, Yarema K J,Chatterjee S. Improved intervention of atherosclerosis and cardiac hypertrophy through biodegradable polymer-encapsulated delivery of glycosphingolipid inhibitor[J]. Biomaterials, 2015, 64:125-135.
[50] Wu T, Chen X Y, Wang Y, Xiao H, Peng Y, Lin L T, Xia W H, Long M, Tao J,Shuai X T. Aortic plaque-targeted andrographolide delivery with oxidation-sensitive micelle effectively treats atherosclerosis via simultaneous ROS capture and anti-inflammation[J].Nanomedicine, 2018, 14(7):2215-2226.
[51] Hyafil F, Laissy J P, Mazighi M, Tchetche D, Louedec L, Adle-Biassette H, Chillon S, Henin D, Jacob M P, Letourneur D,Feldman L J. Ferumoxtran-10-enhanced MRI of the hypercholesterolemic rabbit aorta:Relationship between signal loss and macrophage infiltration[J].Arteriosclerosis, Thrombosis, and Vascular Biology, 2006, 26(1):176-181.
[52] Wang J Q, Liu H, Liu Y, Chu C C, Yang Y Y, Zeng Y, Zhang W G,Liu G. Eumelanin-Fe₃O₄ hybrid nanoparticles for enhanced MR/PA imaging-assisted local photothermolysis[J]. Biomaterials Science, 2018, 6(3):586-595.
[53] He C B, Hu Y P, Yin L C, Tang C,Yin C H. Effects of particle size and surface charge on cellular uptake and biodistribution of polymeric nanoparticles[J]. Biomaterials, 2010, 31(13):3657-3666.
[54] Yan F, Yang W, Li X, Liu H M, Nan X, Xie L S, Zhou D L, Xie G X, Wu J R, Qiu B S, Liu X,Zheng H R. Magnetic resonance imaging of atherosclerosis using CD81-targeted microparticles of iron oxide in mice[J]. Biomed Research International, 2015:758616.
[55] Kao C W, Wu P T, Liao M Y, Chung I J, Yang K C, Tseng W I,Yu J. Magnetic nanoparticles conjugated with peptides derived from monocyte chemoattractant protein-1 as a tool for targeting atherosclerosis[J]. Pharmaceutics, 2018, 10(2),62.
[56] Voros S, Rinehart S, Qian Z, Joshi P, Vazquez G, Fischer C, Belur P, Hulten E,Villines T C. Coronary atherosclerosis imaging by coronary CT angiography:current status, correlation with intravascular interrogation and meta-analysis[J]. JACC Cardiovascular Imaging, 2011, 4(5):537-548.
[57] Torchilin V P, Frank-Kamenetsky M D,Wolf G L. CT visualization of blood pool in rats by using long-circulating, iodine-containing micelles[J]. Academic Radiology, 1999, 6(1):61-65.
[58] Chhour P, Naha P C, O'neill S M, Litt H I, Reilly M P, Ferrari V A,Cormode D P. Labeling monocytes with gold nanoparticles to track their recruitment in atherosclerosis with computed tomography[J]. Biomaterials, 2016, 87:93-103.
[59] Damiano M G, Mutharasan R K, Tripathy S, Mcmahon K M,Thaxton C S. Templated high density lipoprotein nanoparticles as potential therapies and for molecular delivery[J]. Advanced Drug Delivery Reviews, 2013, 65(5):649-662.
[60] Li L, Pang X,Liu G. Near-infrared light-triggered polymeric nanomicelles for cancer therapy and imaging[J]. ACS Biomaterials Science & Engineering, 2018, 4(6):1928-1941.
[61] Qiao R R, Qiao H Y, Zhang Y, Wang Y B, Chi C W, Tian J, Zhang L F, Cao F,Gao M Y. Molecular imaging of vulnerable atherosclerotic plaques in vivo with osteopontin-specific upconversion nanoprobes[J]. American Chemical Society Nano, 2017, 11(2):1816-1825.
[62] Marrache S,Dhar S. Biodegradable synthetic high-density lipoprotein nanoparticles for atherosclerosis[J]. Proceedings of the National Academy of Sciences of the United States of America, 2013, 110(23):9445-9450.
[63] Sun X X, Li W, Zhang X Y, Qi M, Zhang Z P, Zhang X E,Cui Z Q. In vivo targeting and imaging of atherosclerosis using multifunctional virus-like particles of simian virus 40[J]. Nano Letters, 2016, 16(10):6164-6171.
[64] Lu T, Wen S, Cui Y, Ju S H, Li K C,Teng G J. Near-infrared fluorescence imaging of murine atherosclerosis using an oxidized low density lipoprotein-targeted fluorochrome[J]. The International of Journal Cardiovascular Imaging, 2014, 30(1):221-231.
[65] Evans N R, Tarkin J M, Chowdhury M M, Warburton E A,Rudd J H. PET imaging of atherosclerotic disease:Advancing plaque assessment from anatomy to pathophysiology[J]. Current Atherosclerosis Reports, 2016, 18(6):30.
[66] Nahrendorf M, Zhang H, Hembrador S, Panizzi P, Sosnovik D E, Aikawa E, Libby P, Swirski F K,Weissleder R. Nanoparticle PET-CT imaging of macrophages in inflammatory atherosclerosis[J]. Circulation, 2008, 117(3):379-387.
[67] Majmudar M D, Yoo J, Keliher E J, Truelove J J, Iwamoto Y, Sena B, Dutta P, Borodovsky A, Fitzgerald K, Di Carli M F, Libby P, Anderson D G, Swirski F K, Weissleder R,Nahrendorf M. Polymeric nanoparticle PET/MR imaging allows macrophage detection in atherosclerotic plaques[J]. Circulation Research, 2013, 112(5):755-761.
[68] Beldman T J, Senders M L, Alaarg A, Perez-Medina C, Tang J, Zhao Y, Fay F, Deichmoller J, Born B, Desclos E, Van Der Wel N N, Hoebe R A, Kohen F, Kartvelishvily E, Neeman M, Reiner T, Calcagno C, Fayad Z A, De Winther M P J, Lutgens E, Mulder W J M,Kluza E. Hyaluronan nanoparticles selectively target plaque-associated macrophages and improve plaque stability in atherosclerosis[J]. American Chemical Society Nano, 2017, 11(6):5785-5799.
[69] Liang M M, Tan H, Zhou J, Wang T, Duan D,Fan K,He J Y,Cheng D F,Shi H C,Choi H S,Yan X Y.Bioengineered H-ferritin nanocages for quantitative imaging of vulnerable plaques in atherosclerosis[J]. American Chemical Society Nano, 2018, 12(9):9300-9308.
[70] Woodard P K, Liu Y J, Pressly E D, Luehmann H P, Detering L, Sultan D E, Laforest R, Mcgrath A J, Gropler R J,Hawker C J. Design and modular construction of a polymeric nanoparticle for targeted atherosclerosis positron emission tomography imaging:a story of 25% ⁽⁶⁴⁾Cu-CANF-comb[J]. Pharmaceutical Research, 2016, 33(10):2400-2410.
[71] Silvola J M U, Li X G, Virta J, Marjamaki P, Liljenback H, Hytonen J P, Tarkia M, Saunavaara V, Hurme S, Palani S, Hakovirta H, Yla-Herttuala S, Saukko P, Chen Q, Low P S, Knuuti J, Saraste A,Roivainen A. Aluminum fluoride-18 labeled folate enables in vivo detection of atherosclerotic plaque inflammation by positron emission tomography[J]. Scientific Reports, 2018, 8(1):9720.
[72] Steinl D C,Kaufmann B A. Ultrasound imaging for risk assessment in atherosclerosis[J]. International Journal of Molecular Sciences, 2015, 16(5):9749-9769.
[73] Yoon Y I, Pang X, Jung S, Zhang G, Kong M, Liu G,Chen X Y. Smart gold nanoparticle-stabilized ultrasound microbubbles as cancer theranostics[J]. Journal of Materials Chemistry B, 2018, 6(20):3235-3239.
[74] Yan F, Sun Y, Mao Y, Wu M Y, Deng Z T, Li S, Liu X, Xue L, Zheng H R. Ultrasound molecular imaging of atherosclerosis for early diagnosis and therapeutic evaluation through leucocyte-like multiple targeted microbubbles[J]. Theranostics, 2018, 8(7):1879-1891.
[75] Li R J, Sun Y, Wang Q, Yang J, Yang Y, Song L, Wang Z, Luo X H,Su R J. Ultrasound biomicroscopic imaging for interleukin-1 receptor antagonist-inhibiting atherosclerosis and markers of inflammation in atherosclerotic development in apolipoprotein-E knockout mice[J]. Texas Heart Institute Journal, 2015, 42(4):319-326.
[76] Garvin R P, Duryee M J, Klassen L W, Thiele G M,Anderson D R. Ultrasound imaging in an animal model of vascular inflammation following balloon injury[J]. Ultrasound in Medicine Biology, 2012, 38(9):1552-1558.
[77] Anderson D R, Duryee M J, Anchan R K, Garvin R P, Johnston M D, Porter T R, Thiele G M,Klassen L W. Albumin-based microbubbles bind up-regulated scavenger receptors following vascular injury[J]. Journal of Biological Chemistry, 2010, 285(52):40645-40653.
[78] Ferrante E A, Pickard J E, Rychak J, Klibanov A,Ley K. Dual targeting improves microbubble contrast agent adhesion to VCAM-1 and P-selectin under flow[J]. Journal of Controlled Release, 2009, 140(2):100-107.
[79] Wang J Q,Liu G. Imaging nano-bio interactions in the kidney:toward a better understanding of nanoparticle clearance[J]. Angewandte Chemie-International Edition, 2018, 57(12):3008-3010.
[80] Miao T X, Wang J Q, Zeng Y, Liu G,Chen X Y. Polysaccharide-based controlled release systems for therapeutics delivery and tissue engineering:from bench to bedside[J]. Advanced Science (Weinh), 2018, 5(4):1700513.