基于聚酰胺胺树状大分子的纳米诊疗试剂的制备及其肿瘤成像和治疗应用进展
|
摘要
为实现癌症的高效诊疗,生物医用材料领域的研究者在过去数十年中研究了多种可集诊断与治疗为一体的纳米复合材料,其中聚酰胺胺树状大分子由于其精确可控的结构、较好的单分散性以及生物相容性被普遍用作载体构建纳米诊疗试剂。通过树状大分子纳米技术,引入多种成像试剂及治疗试剂,并利用功能化修饰技术可构建具有良好诊疗效能的纳米诊疗材料。这些研究成果为解决癌症精确诊断及高效治疗提供了思路。本文中,笔者对近年来基于聚酰胺胺树状大分子的纳米诊疗试剂的制备及其在肿瘤成像和治疗中的应用进行综述,为开展相关研究提供参考。
In order to achieve efficient theranostic of cancer,researchers in biomedical materials field studied a variety of nanocomposite materials that combined diagnosis and therapy functions in the past decade. Among them,poly( amidoamine) dendrimer is widely used as carrier to build theranostic nanosystem due to its precisely controllable structure,good monodispersity and biocompatibility. Based on dendrimer nanotechnology,various imaging agents and therapeutic agents can be introduced into dendrimer,functionalized modification technique can be further utilized to construct theranostic nanosystem with good theranostic efficiency. These results provide a new idea to solve the problems of precise diagnosis and efficient therapy of cancer.In this review,the latest research progress on fabrication of poly( amidoamine) dendrimer-based theranostic nanosystems and their tumor imaging and therapy application were summarized,to provide basis for further research and development.
In order to achieve efficient theranostic of cancer,researchers in biomedical materials field studied a variety of nanocomposite materials that combined diagnosis and therapy functions in the past decade. Among them,poly( amidoamine) dendrimer is widely used as carrier to build theranostic nanosystem due to its precisely controllable structure,good monodispersity and biocompatibility. Based on dendrimer nanotechnology,various imaging agents and therapeutic agents can be introduced into dendrimer,functionalized modification technique can be further utilized to construct theranostic nanosystem with good theranostic efficiency. These results provide a new idea to solve the problems of precise diagnosis and efficient therapy of cancer.In this review,the latest research progress on fabrication of poly( amidoamine) dendrimer-based theranostic nanosystems and their tumor imaging and therapy application were summarized,to provide basis for further research and development.
引文
[1]MARMD.Advances in cancer therapy:targeted therapies[J].Oncol Res Treat,2016,39(12):758-759.
[2]KARAMI S,YOUNG H A,HENSON D E.Earlier age at diagnosis:another dimension in cancer disparity[J].Cancer Epidemiol,2007,31(1):29-34.
[3]LINDLEY C,MCCUNE J S,THOMASON T E.Perception of chemotherapy side effects cancer versus noncancer patients[J].Cancer Pract,1999,7(2):59-65.
[4]BOELKE E,BUDACH W,JANNI W,et al.Acute side effects of intraoperative electron radiotherapy of breast cancer[J].J Clin Oncol,2012,30(27):112.
[5]PEER D,KARP J M,HONG S P,et al.Nanocarriers as an emerging platform for cancer therapy[J].Nat Nanotechnol,2007,2(12):751-760.
[6]TOMALIA D A.Birth of a new macromolecular architecture:dendrimers as quantized building blocks for nanoscale synthetic polymer chemistry[J].Prog Polym Sci,2005,30(3):294-324.
[7]GUPTA V,NAYAK S K.Dendrimers:a review on synthetic approaches[J].J Appl Pharm Sci,2015,5(3):117-122.
[8]DUFS C,UCHEGBU I F,SCHTZLEIN A G.Dendrimers in gene delivery[J].Adv Drug Deliv Rev,2005,57(15):2177-2202.
[9]AULENTA F,HAYES W,RANNARD S.Dendrimers:a new class of nanoscopic containers and delivery devices[J].Eur Polym J,2003,39(9):1741-1771.
[10]KHANDARE J,CALDERN M.Dendritic polymers for smart drug delivery applications[J].Nanoscale,2015,7(9):3806-3807.
[11]STIRIBA S E,FREY H,HAAG R.Dendritic polymers in biomedical applications:from potential to clinical use in diagnostics and therapy[J].Angew Chem Int Ed,2002,41(8):1329-1334.
[12]WANG Y,GUO R,CAO X,et al.Encapsulation of 2-methoxyestradiol within multifunctional poly(amidoamine)dendrimers for targeted cancer therapy[J].Biomaterials,2011,32(12):3322-3329.
[13]ZHANG M,GUO R,WANG Y,et al.Multifunctional dendrimer/combretastatin A4 inclusion complexes enable in vitro targeted cancer therapy[J].Int J Nanomed,2011,6:2337-2349.
[14]PENG C,ZHENG L,CHEN Q,et al.PEGylated dendrimerentrapped gold nanoparticles for in vivo blood pool and tumor imaging by computed tomography[J].Biomaterials,2012,33(4):1107-1119.
[15]BUHLEIER E,WEHNER W,VOGTLE F.Cascade and nonskidchain-like synthesis of molecular cavity topologies[J].Synthesis,1978,2:155-158.
[16]WOOLEY K L,HAWKER C J,FRECHET J M.Unsymmetrical three-dimensional macromolecules:preparation and characterization of strongly dipolar dendritic macromolecules[J].J Am Chem Soc,1993,115(24):11496-11505.
[17]TOMALIA D A,FRECHET J M.Discovery of dendrimers and dendritic polymers:a brief historical perspective[J].J Polym Sci A,2002,40(16):2719-2728.
[18]UHRICH K E,BOEGEMAN S,FRCHET J M J,et al.The solidphase synthesis of dendritic polyamides[J].Polym Bull,1991,25(5):551-558.
[19]HALLER C,HIZOH I.The cytotoxicity of iodinated radiocontrast agents on renal cells in vitro[J].Invest Radiol,2004,39(3):149-154.
[20]LEE N,HYEON T.Designed synthesis of uniformly sized iron oxide nanoparticles for efficient magnetic resonance imaging contrast agents[J].Chem Soc Rev,2012,41(7):2575-2589.
[21]GALLO J,LONG N J,ABOAGYE E O.Magnetic nanoparticles as contrast agents in the diagnosis and treatment of cancer[J].Chem Soc Rev,2013,42(19):7816-7833.
[22]WEN S,ZHAO Q,AN X,et al.Multifunctional PEGylated multiwalled carbon nanotubes for enhanced blood pool and tumor MR imaging[J].Adv Healthcare Mater,2014,3(10):1568-1577.
[23]CHEN Q,LI K,WEN S,et al.Targeted CT/MR dual mode imaging of tumors using multifunctional dendrimer-entrapped gold nanoparticles[J].Biomaterials,2013,34(21):5200-5209.
[24]IM G H,KIM S M,LEE D G,et al.Fe3O4/Mn O hybrid nanocrystals as a dual contrast agent for both T1and T2-weighted liver MRI[J].Biomaterials,2013,34(8):2069-2076.
[25]HU H,DAI A,SUN J,et al.Aptamer-conjugated Mn3O4@Si O2core-shell nanoprobes for targeted magnetic resonance imaging[J].Nanoscale,2013,5(21):10447-10454.
[26]HUAN G S,LIU J,LIU D,et al.Facile and large-scale synthesis of Gd(OH)3nanorods for MR imaging with low toxicity[J].New J Chem,2012,36(6):1335-1338.
[27]YANG X,HONG H,GRAILER J J,et al.c RGD-functionalized,DOX-conjugated,and64Cu-labeled superparamagnetic iron oxide nanoparticles for targeted anticancer drug delivery and PET/MR imaging[J].Biomaterials,2011,32(17):4151-4160.
[28]CAI H,LI K,LI J,et al.Dendrimer-assisted formation of Fe3O4/Au nanocomposite particles for targeted dual mode CT/MR imaging of tumors[J].Small,2015,11(35):4584-4593.
[29]ZHAO L,ZHU J,CHENG Y,et al.Chlorotoxin-conjugated multifunctional dendrimers labeled with radionuclide131I for single photon emission computed tomography imaging and radiotherapy of gliomas[J].ACS Appl Mater Interfaces,2015,7(35):19798-19808.
[30]CAI J,LI F.Single-photon emission computed tomography tracers for predicting and monitoring cancer therapy[J].Curr Pharm Biotechnol,2013,14(7):693-707.
[31]VAN ETMPT W,MCDERMOTT L,NIJSTEN S,et al.A literature review of electronic portal imaging for radiotherapy dosimetry[J].Radiother Oncol,2008,88(3):289-309.
[32]ZHU J,ZHENG L,WEN S,et al.Targeted cancer theranostics using alpha-tocopheryl succinate-conjugated multifunctional dendrimer-entrapped gold nanoparticles[J].Biomaterials,2014,35(26):7635-7646.
[33]ZHU J,FU F,XIONG Z,et al.Dendrimer-entrapped gold nanoparticles modified with RGD peptide and alpha-tocopheryl succinate enable targeted theranostics of cancer cells[J].Colloids Surf B,2015,133:36-42.
[34]ZHENG L,ZHU J,SHEN M,et al.Targeted cancer cell inhibition using multifunctional dendrimer-entrapped gold nanoparticles[J].Med Chem Comm 2013,4(6):1001-1005.
[35]ZHU J,XIONG Z,SHEN M,et al.Encapsulation of doxorubicin within multifunctional gadolinium-loaded dendrimer nanocomplexes for targeted theranostics of cancer cells[J].RSC Adv,2015,5(38):30286-30296.
[36]CHANG Y,MENG X,ZHAO Y,et al.Novel water-soluble and p H-responsive anticancer drug nanocarriers:doxorubicin-PAMAM dendrimer conjugates attached to superparamagnetic iron oxide nanoparticles(IONPs)[J].J Colloid Interface Sci,2011,363(1):403-409.
[37]CHANG Y,LI Y,MENG X,et al.Dendrimer functionalized water soluble magnetic iron oxide conjugates as dual imaging probe for tumor targeting and drug delivery[J].Polym Chem,2013,4(3):789-794.
[38]LUONG D,SAU S,KESHARWANI P,et al.Polyvalent folatedendrimer-coated iron oxide theranostic nanoparticles for simultaneous magnetic resonance imaging and precise cancer cell targeting[J].Biomacromolecules,2017,18(4):1197-1209.
[39]ZHU J,ZHAO L,CHENG Y,et al.Radionuclide131I-labeled multifunctional dendrimers for targeted SPECT imaging and radiotherapy of tumors[J].Nanoscale,2015,7(43):18169-18178.
[40]HE R,WANG H,SU Y,et al.Incorporating131I into a PAMAM(G5.0)dendrimerconjugate:design of a theranostic nanosensor for medullary thyroid carcinoma[J].RSC Adv,2017,7(26):16181-16188.
[41]MENDOZA-NAVA H,FERRO-FLORES G,RAMREZ F M,et al.177Lu-dendrimer conjugated to folate and bombesin with gold nanoparticles in the dendritic cavity:a potential theranostic radiopharmaceutical[J].J Nanomater,2016,http://dx.doi.org/10.1155/2016/1039258.
[42]WEI P,CHEN J,HU Y,et al.Dendrimer-stabilized gold nanostars as a multifunctional theranostic nanoplatform for CT imaging,photothermal therapy,and gene silencing of tumors[J].Adv Healthcare Mater,2016,5(24):3203-3213.
[43]WONG P T,CHEN D,TANG S,et al.Modular integration of upconverting nanocrystal-dendrimer composites for folate receptorspecific NIR imaging and light-triggered drug release[J].Small,2015,11(45):6078-6090.
[2]KARAMI S,YOUNG H A,HENSON D E.Earlier age at diagnosis:another dimension in cancer disparity[J].Cancer Epidemiol,2007,31(1):29-34.
[3]LINDLEY C,MCCUNE J S,THOMASON T E.Perception of chemotherapy side effects cancer versus noncancer patients[J].Cancer Pract,1999,7(2):59-65.
[4]BOELKE E,BUDACH W,JANNI W,et al.Acute side effects of intraoperative electron radiotherapy of breast cancer[J].J Clin Oncol,2012,30(27):112.
[5]PEER D,KARP J M,HONG S P,et al.Nanocarriers as an emerging platform for cancer therapy[J].Nat Nanotechnol,2007,2(12):751-760.
[6]TOMALIA D A.Birth of a new macromolecular architecture:dendrimers as quantized building blocks for nanoscale synthetic polymer chemistry[J].Prog Polym Sci,2005,30(3):294-324.
[7]GUPTA V,NAYAK S K.Dendrimers:a review on synthetic approaches[J].J Appl Pharm Sci,2015,5(3):117-122.
[8]DUFS C,UCHEGBU I F,SCHTZLEIN A G.Dendrimers in gene delivery[J].Adv Drug Deliv Rev,2005,57(15):2177-2202.
[9]AULENTA F,HAYES W,RANNARD S.Dendrimers:a new class of nanoscopic containers and delivery devices[J].Eur Polym J,2003,39(9):1741-1771.
[10]KHANDARE J,CALDERN M.Dendritic polymers for smart drug delivery applications[J].Nanoscale,2015,7(9):3806-3807.
[11]STIRIBA S E,FREY H,HAAG R.Dendritic polymers in biomedical applications:from potential to clinical use in diagnostics and therapy[J].Angew Chem Int Ed,2002,41(8):1329-1334.
[12]WANG Y,GUO R,CAO X,et al.Encapsulation of 2-methoxyestradiol within multifunctional poly(amidoamine)dendrimers for targeted cancer therapy[J].Biomaterials,2011,32(12):3322-3329.
[13]ZHANG M,GUO R,WANG Y,et al.Multifunctional dendrimer/combretastatin A4 inclusion complexes enable in vitro targeted cancer therapy[J].Int J Nanomed,2011,6:2337-2349.
[14]PENG C,ZHENG L,CHEN Q,et al.PEGylated dendrimerentrapped gold nanoparticles for in vivo blood pool and tumor imaging by computed tomography[J].Biomaterials,2012,33(4):1107-1119.
[15]BUHLEIER E,WEHNER W,VOGTLE F.Cascade and nonskidchain-like synthesis of molecular cavity topologies[J].Synthesis,1978,2:155-158.
[16]WOOLEY K L,HAWKER C J,FRECHET J M.Unsymmetrical three-dimensional macromolecules:preparation and characterization of strongly dipolar dendritic macromolecules[J].J Am Chem Soc,1993,115(24):11496-11505.
[17]TOMALIA D A,FRECHET J M.Discovery of dendrimers and dendritic polymers:a brief historical perspective[J].J Polym Sci A,2002,40(16):2719-2728.
[18]UHRICH K E,BOEGEMAN S,FRCHET J M J,et al.The solidphase synthesis of dendritic polyamides[J].Polym Bull,1991,25(5):551-558.
[19]HALLER C,HIZOH I.The cytotoxicity of iodinated radiocontrast agents on renal cells in vitro[J].Invest Radiol,2004,39(3):149-154.
[20]LEE N,HYEON T.Designed synthesis of uniformly sized iron oxide nanoparticles for efficient magnetic resonance imaging contrast agents[J].Chem Soc Rev,2012,41(7):2575-2589.
[21]GALLO J,LONG N J,ABOAGYE E O.Magnetic nanoparticles as contrast agents in the diagnosis and treatment of cancer[J].Chem Soc Rev,2013,42(19):7816-7833.
[22]WEN S,ZHAO Q,AN X,et al.Multifunctional PEGylated multiwalled carbon nanotubes for enhanced blood pool and tumor MR imaging[J].Adv Healthcare Mater,2014,3(10):1568-1577.
[23]CHEN Q,LI K,WEN S,et al.Targeted CT/MR dual mode imaging of tumors using multifunctional dendrimer-entrapped gold nanoparticles[J].Biomaterials,2013,34(21):5200-5209.
[24]IM G H,KIM S M,LEE D G,et al.Fe3O4/Mn O hybrid nanocrystals as a dual contrast agent for both T1and T2-weighted liver MRI[J].Biomaterials,2013,34(8):2069-2076.
[25]HU H,DAI A,SUN J,et al.Aptamer-conjugated Mn3O4@Si O2core-shell nanoprobes for targeted magnetic resonance imaging[J].Nanoscale,2013,5(21):10447-10454.
[26]HUAN G S,LIU J,LIU D,et al.Facile and large-scale synthesis of Gd(OH)3nanorods for MR imaging with low toxicity[J].New J Chem,2012,36(6):1335-1338.
[27]YANG X,HONG H,GRAILER J J,et al.c RGD-functionalized,DOX-conjugated,and64Cu-labeled superparamagnetic iron oxide nanoparticles for targeted anticancer drug delivery and PET/MR imaging[J].Biomaterials,2011,32(17):4151-4160.
[28]CAI H,LI K,LI J,et al.Dendrimer-assisted formation of Fe3O4/Au nanocomposite particles for targeted dual mode CT/MR imaging of tumors[J].Small,2015,11(35):4584-4593.
[29]ZHAO L,ZHU J,CHENG Y,et al.Chlorotoxin-conjugated multifunctional dendrimers labeled with radionuclide131I for single photon emission computed tomography imaging and radiotherapy of gliomas[J].ACS Appl Mater Interfaces,2015,7(35):19798-19808.
[30]CAI J,LI F.Single-photon emission computed tomography tracers for predicting and monitoring cancer therapy[J].Curr Pharm Biotechnol,2013,14(7):693-707.
[31]VAN ETMPT W,MCDERMOTT L,NIJSTEN S,et al.A literature review of electronic portal imaging for radiotherapy dosimetry[J].Radiother Oncol,2008,88(3):289-309.
[32]ZHU J,ZHENG L,WEN S,et al.Targeted cancer theranostics using alpha-tocopheryl succinate-conjugated multifunctional dendrimer-entrapped gold nanoparticles[J].Biomaterials,2014,35(26):7635-7646.
[33]ZHU J,FU F,XIONG Z,et al.Dendrimer-entrapped gold nanoparticles modified with RGD peptide and alpha-tocopheryl succinate enable targeted theranostics of cancer cells[J].Colloids Surf B,2015,133:36-42.
[34]ZHENG L,ZHU J,SHEN M,et al.Targeted cancer cell inhibition using multifunctional dendrimer-entrapped gold nanoparticles[J].Med Chem Comm 2013,4(6):1001-1005.
[35]ZHU J,XIONG Z,SHEN M,et al.Encapsulation of doxorubicin within multifunctional gadolinium-loaded dendrimer nanocomplexes for targeted theranostics of cancer cells[J].RSC Adv,2015,5(38):30286-30296.
[36]CHANG Y,MENG X,ZHAO Y,et al.Novel water-soluble and p H-responsive anticancer drug nanocarriers:doxorubicin-PAMAM dendrimer conjugates attached to superparamagnetic iron oxide nanoparticles(IONPs)[J].J Colloid Interface Sci,2011,363(1):403-409.
[37]CHANG Y,LI Y,MENG X,et al.Dendrimer functionalized water soluble magnetic iron oxide conjugates as dual imaging probe for tumor targeting and drug delivery[J].Polym Chem,2013,4(3):789-794.
[38]LUONG D,SAU S,KESHARWANI P,et al.Polyvalent folatedendrimer-coated iron oxide theranostic nanoparticles for simultaneous magnetic resonance imaging and precise cancer cell targeting[J].Biomacromolecules,2017,18(4):1197-1209.
[39]ZHU J,ZHAO L,CHENG Y,et al.Radionuclide131I-labeled multifunctional dendrimers for targeted SPECT imaging and radiotherapy of tumors[J].Nanoscale,2015,7(43):18169-18178.
[40]HE R,WANG H,SU Y,et al.Incorporating131I into a PAMAM(G5.0)dendrimerconjugate:design of a theranostic nanosensor for medullary thyroid carcinoma[J].RSC Adv,2017,7(26):16181-16188.
[41]MENDOZA-NAVA H,FERRO-FLORES G,RAMREZ F M,et al.177Lu-dendrimer conjugated to folate and bombesin with gold nanoparticles in the dendritic cavity:a potential theranostic radiopharmaceutical[J].J Nanomater,2016,http://dx.doi.org/10.1155/2016/1039258.
[42]WEI P,CHEN J,HU Y,et al.Dendrimer-stabilized gold nanostars as a multifunctional theranostic nanoplatform for CT imaging,photothermal therapy,and gene silencing of tumors[J].Adv Healthcare Mater,2016,5(24):3203-3213.
[43]WONG P T,CHEN D,TANG S,et al.Modular integration of upconverting nanocrystal-dendrimer composites for folate receptorspecific NIR imaging and light-triggered drug release[J].Small,2015,11(45):6078-6090.