膠質瘤納米治療技術的研究現狀與發展前景

涂艷陽，祁 婧，張永生,楊宏偉

(第四軍醫大學：1唐都醫院實驗外科，2唐都醫院，陜西 西安 710038；3哈佛醫學院布列根與婦女醫院神經外科，美國 波士頓 02115)

·述評·

膠質瘤納米治療技術的研究現狀與發展前景

涂艷陽1，祁 婧1，張永生2,楊宏偉3

(第四軍醫大學：1唐都醫院實驗外科，2唐都醫院，陜西 西安 710038；3哈佛醫學院布列根與婦女醫院神經外科，美國 波士頓 02115)

神經膠質瘤是顱內最常見的惡性腫瘤，占所有顱內腫瘤的46%. 由于神經膠質瘤呈侵潤性生長，故僅通過傳統手術難以做到全部切除，因此，采用新技術手段提高現有早期診斷、療效預測以及有效治療策略是亟待解決的首要問題. 隨著納米生物醫學的飛速發展，納米技術已經在膠質瘤的預測、診斷、影像及治療等領域顯示出巨大的優勢. 本研究綜述了納米載體、膠質瘤納米治療機理以及膠質瘤納米診斷和治療領域的主要研究進展.

膠質瘤;納米載體;化療藥物

0 引言

長期以來,惡性腫瘤的診斷和治療一直是醫學和生命科學研究領域的熱點和難點. 神經膠質瘤是顱內最常見的惡性腫瘤，約占所有顱內腫瘤的46%，診斷后的膠質瘤患者生存期僅有12～14個月. 由于神經膠質瘤呈侵潤性生長，故僅通過傳統手術無法有效治愈，難以做到腫瘤的全部切除，故多采用聯合治療，配以放療和化療來降低復發率，延長生存期[1]. 但是，目前的化療藥物和放療主要針對生長期細胞，而對處于非生長期的神經膠質瘤干癌細胞幾乎沒有作用[1]. 所以侵潤性極強的神經膠質瘤具有低治愈、高復發的特點，這也成為至今無法攻克的一大難題[1].

目前，對于惡性膠質瘤，臨床上面臨的主要問題是腫瘤的診斷與治療的分離. 集多種性能于一體的診療劑(Theranostics)的設計和應用有望解決這個難題[2]. 智能化的診療劑能有效提高治療疾病的選擇和特異性，達到高的局部毒性和低的副作用. 因此，針對膠質瘤的診斷與治療分離這一臨床主要問題，能夠利用磁性納米粒子、金納米棒[3]實現惡性膠質瘤的分子影像和個性化治療. 隨著納米生物醫學的快速發展，納米技術已經在膠質瘤的預防、診斷、影像和治療等領域作出巨大的貢獻. 本研究綜述了納米載體、膠質瘤納米治療機理以及膠質瘤納米診斷和治療領域的主要研究進展.

1 納米載體

納米載體來源于生物、有機和無機物，用以探究各種生物學機制和解決生物學問題. 納米載體多為脂類和聚合材料構成，另外還開發出各種潛在新材料包括巨噬細胞特異的納米粒子[4]，靶向磁納米粒子[5-6]、金納米材料[7]、功能化的碳納米管[8]、二氧化硅顆粒[9-10]及修飾的植物病毒[11]等.

聚合物材料是納米材料中的最大的一類，包括許多亞型，如核-殼粒子、可生物降解的聚乳酸-共-羥基乙酸(PLGA)納米顆粒、水凝膠納米粒子. 聚合物膠束是非交聯粒子，涉及共聚物顆粒、單一聚合物鏈包含不止一個相同分子. 一個簡單的聚合物膠束包含許多二親聚合物，模擬膠束的尾巴和頭部. 這些聚合物在疏水性藥物周圍自發形成膠束. 具有受控尺寸和形狀的聚合物納米粒子允許細胞附著同時可以防止內在化，從而使細胞對藥物的有效載荷攜帶到遞送第二個站點. 因此針對循環腫瘤細胞，就可以使用具有長循環時間的聚合物. 水凝膠納米粒子，也被稱為納米凝膠，在親水環境中接觸水時交聯在接觸時膨脹[12]. 納米凝膠可以共價或非共價結合的藥物或靶向配體，還可以響應于環境因素膨脹或縮小，如pH或溫度.

脂類是可以自組織囊泡(脂質雙分子層和脂質體)的二親性小分子、膠束或脂質復合物(無定形顆粒[13]. 這些載體可以修飾為靶向遞送水溶性和不溶性的治療劑. 尺寸、承載能力和定位功能等屬性也可以被修飾. 再加上適當的目標配體，如整聯蛋白結合肽，脂質體可在血管生成過程在腫瘤血管系統積累[14]且可遞送有效治療載荷. 金納米顆粒已經被用于熱燒蝕治療[15]，通過以熱的形式釋放能量至近紅外光響應誘導腫瘤血管的凝結以及可協同增加其他靶向療法的治療效果[16]. 金納米顆粒也可以作為支架連接多個配體[17]. 其他納米材料類，如納米鐵顆粒和碳納米顆粒，也同樣應用到藥物遞送治療[18].

2 治療機理

納米粒子治療劑從小分子藥物或生物大分子的載體(如蛋白質或siRNA)[19-28]到成像和熱吸收載體. 納米顆粒裝載藥物的優點包括疾病位點靶向藥物、觸發藥物在身體的特定位置釋放[29-30]以及改變藥物的藥代動力學特性以增加其在疾病部位的半衰期[31]. 這些能力會減少脫靶效應和降低藥物劑量[32-33]. 納米粒子具備更多復雜的藥物遞送能力，例如遞送含有調節血管系統分子的藥物[34-35]，藥物前體以及其激活酶[36-37]或靶向配體免疫治療[38-41]. 同時，生理微環境[42-43]或可替代的外部刺激(超聲[44-46]、光[47-49]或射頻電磁場[50])也可以觸發局部藥物釋放.

納米粒子的治療作用不僅僅是藥物的封裝和遞送. Thermoablative治療(加熱組織以殺死腫瘤細胞)、磁場、紅外線和無線電頻率等技術可以通過激活納米材料局部增強對患病組織的作用[15,51-53]. 但是所有這些外部觸發作用既有優點也有局限性. 例如，電磁場能深入(>15 cm)滲透，但它們難以聚焦. 高強度聚焦超聲(HIFU)能深入組織且可聚焦到幾個毫米的體積，但是當應用到骨骼或氣體填充的器官時其功能則會減弱[54]. 紅外燈的波長范圍為750～1300 nm，穿透組織且可達1 cm的深度，之后滲透大幅減小[55]. 因此紅外線主要適用于病變靠近皮膚表面的情況.

3 膠質瘤納米治療技術

隨著納米技術在20世紀80年代的迅速發展，醫學領域便利用這一新的技術開發出新的治療劑. 對于腦腫瘤，納米技術方法可以通過血腦屏障便于藥物遞送[56-57]. 納米顆粒類似生物大分子，不能像生物小分子一樣隨意擴散到組織[58]. 該納米粒子在腫瘤內積累的能力是由于增強的滲透性和滯留效果. 增強的滲透性并且保留效果是由活躍的血管生成和血管結構改變而部分介導的，這導致即使在血清水平下降的情況下，納米顆粒仍滯留在腫瘤組織[59]. 此外，納米顆粒可以“保護”遞送的目標免于周圍環境的干擾而到達靶位. 例如，靜脈注射時亞甲藍很快會被高鐵血紅蛋白還原酶催化失活. 這種現象可以通過利用納米顆粒遞送亞甲藍到腫瘤組織的方法來避免[60-62]. 納米顆粒也可以用于遞送化療藥物穿過血腦屏障，如阿霉素[63-64]. 納米顆粒遞送阿霉素的療法具有降低毒性與改善多形性成膠質細胞瘤的異種移植物模型中抗腫瘤細胞的功效[63-65].

在神經外科領域，正在研究納米粒子用于腦成像[66]. 另外，氧化鐵納米顆粒可裝載熒光染料，實現腫瘤的可視化外科手術[58,67-69].

納米顆粒用于藥物遞送的能力是未來治療腦腫瘤的方向. 某些化療藥物，如阿霉素和紫杉醇，可利用固體脂質納米粒封裝，對于腫瘤組織有較高的可利用性并盡量減少全身性毒性[70]. 由于病毒載體的免疫反應以及脂質體效率較低，研究人員也正在研究納米粒子用于基因治療[58]. 例如，含APO2/TRAIL質粒裝載到納米顆粒可以在腫瘤組織中累積，增加C6膠質瘤小鼠生存率[71].

4 展望

納米醫學開創了膠質瘤早期診斷與靶向治療策略的新時代. 膠質瘤的納米治療是利用納米材料靶向識別并殺滅惡性膠質瘤細胞的個性化治療. 利用納米材料特性，同時結合腦膠質瘤干細胞的特異靶點及其所特異的分子信號通路來設計納米治療探針已經成為一個新的熱點研究. 但是膠質瘤納米治療所面臨的許多問題還有待于進一步的研究；如何構建體內靶向分子探針、放大信號、消除探針潛在毒性正是當今膠質瘤納米治療需要解決的關鍵問題；另外，納米探針作為小分子或多肽探針連接在納米粒子表面后，作為信號源的納米粒子較高的表面可能會改變其分子構象或者屏蔽其結合基團，所以兩者相互作用的長期機制還不明確，仍需進一步的探究進行驗證. 因此，納米治療技術在人體應用還有很多值得挖掘和深究的方向. 如今的膠質瘤納米診斷和治療技術正飛速發展，納米科技也為攻克膠質瘤提供了一種全新的治療策略.

[1] Furnari FB, Fenton T, Bachoo RM, et al. Malignant astrocytic glioma: genetics, biology, and paths to treatment[J]. Genes Dev,2007,21(21):2683-2710.

[2] Kelkar SS, Reineke TM. Theranostics: combining imaging and therapy[J]. Bioconjug Chem,2011,22(10):1879-1903.

[3] Schroeder A, Heller DA, Winslow MM, et al. Treating metastatic cancer with nanotechnology[J]. Nat Rev Cancer,2012,12(1):39-50.

[4] Zhang W, Zhu XD, Sun HC, et al. Depletion of tumor-associated macrophages enhances the effect of sorafenib in metastatic liver cancer models by antimetastatic and antiangiogenic effects[J]. Clin Cancer Res,2010,16(13):3420-3430.

[5] Scarberry KE, Dickerson EB, Zhang ZJ, et al. Selective removal of ovarian cancer cells from human ascites fluid using magnetic nanoparticles[J]. Nanomedicine,2010,6(3):399-408.

[6] Galanzha EI, Shashkov EV, Kelly T, et al. In vivo magnetic enrichment and multiplex photoacoustic detection of circulating tumour cells[J]. Nat Nanotechnol,2009,4(12):855-860.[7] Coffey DS, Getzenberg RH, DeWeese TL. Hyperthermic biology and cancer therapies: a hypothesis for the “Lance Armstrong effect”[J]. JAMA,2006,296(4):445-448.

[8] Ruggiero A, Villa CH, Bander E, et al. Paradoxical glomerular filtration of carbon nanotubes[J]. Proc Natl Acad Sci U S A,2010,107(27):12369-12374.

[9] Slowing II, Trewyn BG, Lin VS. Mesoporous silica nanoparticles for intracellular delivery of membrane-impermeable proteins[J]. J Am Chem Soc,2007,129(28):8845-8849.

[10] Gratton SE, 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(33):11613-11618.

[11] Brunel FM, Lewis JD, Destito G, et al. Hydrazone ligation strategy to assemble multifunctional viral nanoparticles for cell imaging and tumor targeting[J]. Nano Lett,2010,10(3):1093-1097.

[12] Murphy EA, Majeti BK, Mukthavaram R, et al. Targeted nanogels: a versatile platform for drug delivery to tumors[J]. Mol Cancer Ther,2011,10(6):972-982.

[13] Schroeder A, Kost J, Barenholz Y. Ultrasound, liposomes, and drug delivery: principles for using ultrasound to control the release of drugs from liposomes[J]. Chem Phys Lipids,2009,162(1-2):1-16.

[14] Liu XQ, Song WJ, Sun TM, et al. Targeted delivery of antisense inhibitor of miRNA for antiangiogenesis therapy using cRGD-functionalized nanoparticles[J]. Mol Pharm,2011,8(1):250-259.

[15] Lal S, Clare SE, Halas NJ. Nanoshell-enabled photothermal cancer therapy: impending clinical impact[J]. Acc Chem Res,2008,41(12):1842-1851.

[16] Park JH, von Maltzahn G, Xu MJ, et al. Cooperative nanomaterial system to sensitize, target, and treat tumors[J]. Proc Natl Acad Sci U S A,2010,107(3):981-986.

[17] Libutti SK, Paciotti GF, Byrnes AA, et al. Phase I and pharmacokinetic studies of CYT-6091, a novel PEGylated colloidal gold-rhTNF nanomedicine[J]. Clin Cancer Res,2010,16(24):6139-6149.

[18] Kam NW, Liu Z, Dai H. Functionalization of carbon nanotubes via cleavable disulfide bonds for efficient intracellular delivery of siRNA and potent gene silencing[J]. J Am Chem Soc,2005,127(36):12492-12493.

[19] Wang J, Tian S, Petros RA, et al. The complex role of multivalency in nanoparticles targeting the transferrin receptor for cancer therapies[J]. J Am Chem Soc,2010,132(32):11306-11313.

[20] Li Z, Xiang J, Zhang W, et al. Nanoparticle delivery of anti-metastatic NM23-H1 gene improves chemotherapy in a mouse tumor model[J]. Cancer Gene Ther,2009,16(5):423-429.

[21] Davis ME, Zuckerman JE, Choi CH, et al. Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles[J]. Nature,2010,464(7291):1067-1070.

[22] Li SD, Chono S, Huang L. Efficient oncogene silencing and metastasis inhibition via systemic delivery of siRNA[J]. Mol Ther,2008,16(5):942-946.

[23] Ma L, Young J, Prabhala H,et al. miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis[J]. Nature Cell Biol,2010,12(3)：247-256.

[24] Ma L, Teruya-Feldstein J, Weinberg RA. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer[J]. Nature,2007,449(7163):682-688.

[25] Ma L, Reinhardt F, Pan E, et al. Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model[J]. Nat Biotechnol,2010,28(4):341-347.[26] Gupta RA, Shah N, Wang KC, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis[J]. Nature,2010,464(7291):1071-1076.

[27] Pecot CV, Calin GA, Coleman RL, et al. RNA interference in the clinic: challenges and future directions[J]. Nat Rev Cancer,2011,11(1):59-67.

[28] Zamora-Avila DE, Zapata-Benavides P, Franco-Molina MA, et al. WT1 gene silencing by aerosol delivery of PEI-RNAi complexes inhibits B16-F10 lung metastases growth[J]. Cancer Gene Ther,2009,16(12):892-899.

[29] Park JH, von Maltzahn G, Ong LL, et al. Cooperative nanoparticles for tumor detection and photothermally triggered drug delivery[J]. Adv Mater,2010,22(8):880-885.

[30] von Maltzahn G, Centrone A, Park JH, et al. SERS-coded gold nanorods as a multifunctional platform for densely multiplexed near-infrared imaging and photothermal heating[J]. Adv Mater,2009,21(31):3175-3180.

[31] Gabizon A, Shmeeda H, Barenholz Y. Pharmacokinetics of pegylated liposomal Doxorubicin: review of animal and human studies[J]. Clin Pharmacokinet,2003,42(5):419-436.

[32] Safra T, Muggia F, Jeffers S, et al. Pegylated liposomal doxorubicin (doxil): reduced clinical cardiotoxicity in patients reaching or exceeding cumulative doses of 500 mg/m2[J]. Ann Oncol,2000,11(8):1029-1033.

[33] Lee J, Sohn JW, Zhang Y, et al. Nucleic acid-binding polymers as anti. inflammatory agents[J]. Proc Natl Acad Sci U S A,2011,108(34):14055-14060.

[34] Hood JD, Bednarski M, Frausto R, et al. Tumor regression by targeted gene delivery to the neovasculature[J]. Science,2002,296(5577):2404-2407.

[35] Murphy EA, Majeti BK, Barnes LA, et al. Nanoparticle-mediated drug delivery to tumor vasculature suppresses metastasis[J]. Proc Natl Acad Sci U S A,2008,105(27):9343-9348.

[36] Gupta PB, Onder TT, Jiang G, et al. Identification of selective inhibitors of cancer stem cells by high-throughput screening[J]. Cell,2009,138(4):645-659.

[37] Aboody KS, Bush RA, Garcia E, et al. Development of a tumor-selective approach to treat metastatic cancer[J]. PLoS ONE,2006,1:e23.

[38] Müller A, Homey B, Soto H, et al. Involvement of chemokine receptors in breast cancer metastasis[J] Nature,2001,410(6824):50-56.

[39] Peer D, Margalit R. Loading mitomycin C inside long circulating hyaluronan targeted nano-liposomes increases its antitumor activity in three mice tumor models[J]. Int J Cancer,2004,108(5):780-789.

[40] Poon Z, Chen S, Engler AC, et al. Ligand-clustered “patchy” nanoparticles for modulated cellular uptake and in vivo tumor targeting[J]. Angew Chem Int Ed Engl,2010,49(40):7266-7270.

[41] Ali OA, Emerich D, Dranoff G, et al. In situ regulation of DC subsets and T cells mediates tumor regression in mice[J]. Sci Transl Med,2009,1(8):8ra19.

[42] Timko BP, Dvir T, Kohane DS. Remotely triggerable drug delivery systems[J]. Adv Mater,2010,22(44):4925-4943.

[43] Fischel-Ghodsian F, Brown L, Mathiowitz E, et al. Enzymatically controlled drug delivery[J]. Proc Natl Acad Sci U S A,1988,85(7):2403-2406.[44] Schroeder A, Avnir Y, Weisman S, et al. Controlling liposomal drug release with low frequency ultrasound: mechanism and feasibility[J]. Langmuir,2007,23(7):4019-4025.

[45] Dromi S, Frenkel V, Luk A, et al. Pulsed-high intensity focused ultrasound and low temperature-sensitive liposomes for enhanced targeted drug delivery and antitumor effect[J]. Clin Cancer Res,2007,13(9):2722-2727.

[46] Burks SR, Ziadloo A, Hancock HA, et al. Investigation of cellular and molecular responses to pulsed focused ultrasound in a mouse model[J]. PLoS ONE,2011,6(9):e24730.

[47] Lu J, Choi E, Tamanoi F, et al. Light-activated nanoimpeller-controlled drug release in cancer cells[J]. Small,2008,4(4):421-426.

[48] Kuruppuarachchi M, Savoie H, Lowry A, et al. Polyacrylamide nanoparticles as a delivery system in photodynamic therapy[J]. Mol Pharm,2011,8(3):920-931.

[49] Wu G, Mikhailovsky A, Khant HA, et al. Remotely triggered liposome release by near-infrared light absorption via hollow gold nanoshells[J]. J Am Chem Soc,2008,130(26):8175-8177.

[50] Hoare T, Timko BP, Santamaria J, et al. Magnetically triggered nanocomposite membranes: a versatile platform for triggered drug release[J]. Nano Lett,2011,11(3):1395-1400.

[51] Bear AS, Kennedy LC, Young JK, et al. Elimination of metastatic melanoma using gold nanoshell-enabled photothermal therapy and adoptive T cell transfer[J]. PLOS One, 2013, 8(7):e69073.

[52] Yang W, Ahmed M, Elian M, et al. Do liposomal apoptotic enhancers increase tumor coagulation and end-point survival in percutaneous radiofrequency ablation of tumors in a rat tumor model[J]. Radiology,2010,257(3):685-696.

[53] Ivkov R, DeNardo SJ, Daum W, et al. Application of high amplitude alternating magnetic fields for heat induction of nanoparticles localized in cancer[J]. Clin Cancer Res,2005,11(19 Pt 2):7093s-7103s.

[54] Kennedy JE. High-intensity focused ultrasound in the treatment of solid tumours[J]. Nat Rev Cancer,2005,5(4):321-327.

[55] International Commission on Non-Ionizing Radiation Protection. ICNIRP statement on far infrared radiation exposure[J]. Health Phys,2006,91(6):630-645.

[56] Ding H, Inoue S, Ljubimov AV, et al. Inhibition of brain tumor growth by intravenous poly (β-L-malic acid) nanobioconjugate with pH-dependent drug release [corrected][J]. Proc Natl Acad Sci U S A,2010,107(42):18143-18148.

[57] Fujita M, Lee BS, Khazenzon NM, et al. Brain tumor tandem targeting using a combination of monoclonal antibodies attached to biopoly(beta-L-malic acid)[J]. J Control Release,2007,122(3):356-363.

[58] Orringer DA, Koo YE, Chen T, et al. Small solutions for big problems: the application of nanoparticles to brain tumor diagnosis and therapy[J]. Clin Pharmacol Ther,2009,85(5):531-534.

[59] Maeda H. The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting[J]. Adv Enzyme Regul,2001,41:189-207.

[60] Williams JL, Stamp J, Devonshire R, et al. Methylene blue and the photodynamic therapy of superficial bladder cancer[J]. J Photochem Photobiol B,1989,4(2):229-232.

[61] May JM, Qu ZC, Cobb CE. Reduction and uptake of methylene blue by human erythrocytes[J]. Am J Physiol Cell Physiol,2004,286(6):C1390-C1398.

[62] Tang W, Xu H, Kopelman R, et al. Photodynamic characterization and in vitro application of methylene blue-containing nanoparticle platforms[J]. Photochem Photobiol,2005,81(2):242-249.

[63] Kreuter J, Gelperina S. Use of nanoparticles for cerebral cancer[J]. Tumori,2008,94(2):271-277.

[64] Kang C, Yuan X, Zhong Y, et al. Growth inhibition against intracranial C6 glioma cells by stereotactic delivery of BCNU by controlled release from poly(D,L-lactic acid) nanoparticles[J]. Technol Cancer Res Treat,2009,8(1):61-70.

[65] Hekmatara T, Bernreuther C, Khalansky AS, et al. Efficient systemic therapy of rat glioblastoma by nanoparticle-bound doxorubicin is due to antiangiogenic effects[J]. Clin Neuropathol,2009,28(3):153-164.

[66] Varallyay P, Nesbit G, Muldoon LL, et al. Comparison of two superparamagnetic viral-sized iron oxide particles ferumoxides and ferumoxtran-10 with a gadolinium chelate in imaging intracranial tumors[J]. AJNR Am J Neuroradiol,2002,23(4):510-519.

[67] Veiseh O, Sun C, Gunn J, et al. Optical and MRI multifunctional nanoprobe for targeting gliomas[J]. Nano Lett,2005,5(6):1003-1008.

[68] Kircher MF, Mahmood U, King RS, et al. A multimodal nanoparticle for preoperative magnetic resonance imaging and intraoperative optical brain tumor delineation[J]. Cancer Res,2003,63(23):8122-8125.

[69] Jackson H, Muhammad O, Daneshvar H, et al. Quantum dots are phagocytized by macrophages and colocalize with experimental gliomas[J]. Neurosurgery,2007,60(3):524-530.

[70] Wissing SA, Kayser O, Müller RH. Solid lipid nanoparticles for parenteral drug delivery[J]. Adv Drug Deliv Rev,2004,56(9):1257-1272.

[71] Lu W, Sun Q, Wan J, et al. Cationic albumin-conjugated pegylated nanoparticles allow gene delivery into brain tumors via intravenous administration[J]. Cancer Res,2006,66(24):11878-11887.

The current situation and prospect of treating glioma with nanotechnology

TUYan-Yang1,QIJing1,ZHANGYong-Sheng2，YANGHong-Wei3

The Fourth Military Medical University:1Department of Experimental Surgery,2Tangdu Hospital, Xi’an 710038, China;3Neurosurgerons, Brigham and Women’s Hospital, Haward Medical Shool, Boston 02115, America

Neuroglioma is the most common malignancy, accounting for nearly half of all human brain tumors. Operation is still difficult to completely remove because of its invasive growth. Thus, the introduction of new technology to improve current diagnosticis, curative effect forecast and treatment strategies is the major problems to be solved. With the rapid development of nano-biomedicine, nanotechnology has demonstrated its great advantages in the prevention, diagnosis, imaging and treatment of gliomas and other areas. This paper reviews the progress of major nanocarrier, nanoparticle therapy treatment mechanism and nanoparticle diagnostic and therapeutic areas for glioma.

glioma; nanocarrier; chemotherapy drugs

2016-07-18;接受日期:2016-08-04

國家自然科學基金資助項目(No.81572983,No.81272419)

涂艷陽. 博士,副教授,副主任醫師. Tel: 029-84777469 E-mail:tu.fmmu@gmail.com

張永生. 教授,主任醫師,院長. E-mail:zhangys@fmmu.edu.cn

2095-6894(2016)09-01-04

R739.4

A