Aptamer-Functionalized Dendrimer Delivery of Plasmid-Encoding lncRNA MEG3 Enhances Gene Therapy in Castration-Resistant Prostate Cancer

被引：39

作者：

Tai, Zongguang ^{[1
,2
]}

Ma, Jinyuan ^{[1
]}

Ding, Jianing ^{[1
]}

Pan, Huijun ^{[1
]}

Chai, Rongrong ^{[1
]}

Zhu, Congcong ^{[1
]}

Cui, Zhen ^{[1
]}

Chen, Zhongjian ^{[1
]}

Zhu, Quangang ^{[1
]}

机构：

[1] Tongji Univ, Shanghai Skin Dis Hosp, Sch Med, Baode Rd 1278, Shanghai 200443, Peoples R China

[2] Second Mil Med Univ, Changhai Hosp, Dept Pharm, Shanghai 200433, Peoples R China

来源：

INTERNATIONAL JOURNAL OF NANOMEDICINE | 2020年 / 15卷

基金：

中国国家自然科学基金;

关键词：

long non-coding RNA MEG3; castration-resistant prostate cancer; gene therapy; dendrimer; LONG NONCODING RNA; CYCLIN D1; CELL; PROLIFERATION; P53; DISCOVERIES; MUTATIONS; CARCINOMA; APOPTOSIS; MARKER;

D O I：

10.2147/IJN.S282107

中图分类号：

TB3 [工程材料学];

学科分类号：

0805 ; 080502 ;

摘要：

Purpose: The clinical management of patients with castration-resistant prostate cancer (CRPC) is difficult. However, novel treatment methods are gradually being introduced. Considering the adverse effects of traditional treatments, recent studies have investigated gene therapy as a method to combat CRPC; but, the application of long non-coding (lnc) RNA in gene therapy remains scarce, despite their promise. Therefore, it is imperative to develop a system that can efficiently deliver lncRNA for the treatment of CRPC. Here, we investigated the efficacy of a delivery system by introducing the plasmid-encoding tumor suppressor lncRNA MEG3 (pMEG3) in CRPC cells. Materials and Methods: An EpDT3 aptamer-linked poly(amidoamine) (PAMAM) dendrimer targeting EpCAM was used to deliver pMEG3 in CRPC cells. The PAMAM-PEG-EpDT3/pMEG3 nanoparticles (NPs) were tested using in vitro cellular assays including cellular uptake, entry, and CCK-8 measurement, and tumor growth inhibition, histological assessment, and safety evaluations in in vivo animal models. Results: The EpDT3 aptamer promoted endocytosis of PAMAM and PAMAM-PEG-EpDT3 /pMEG3 NPs in CRPC cells. PAMAM-PEG-EpDT3/pMEG3 NPs exhibited a significant anti-CRPC effect, both in vivo and in vitro, when compared to that of unfunctionalized PAMAM-PEG/pMEG3 NPs. Conclusion: PAMAM-PEG-EpDT3/pMEG3 NPs can potentially improve gene therapy in CRPC cells.

引用

页码：10305 / 10320

页数：16

共 49 条

[1] Selective Liposomal Transport through Blood Brain Barrier Disruption in lschemic Stroke Reveals Two Distinct Therapeutic Opportunities [J].

Al-Ahmady, Zahraa S. ;

Jasim, Dhifaf ;

Ahmad, Sabahuddin Syed ;

Wong, Raymond ;

Haley, Michael ;

Coutts, Graham ;

Schiess, Ingo ;

Allan, Stuart M. ;

Kostarelos, Kostas .

ACS NANO, 2019, 13 (11) :12470-12486

[2] LncRNA Meg3 protects endothelial function by regulating the DNA damage response [J].

Ali, Mohamed Sham Shihabudeen Haider ;

Cheng, Xiao ;

Moran, Matthew ;

Haemmig, Stefan ;

Naldrett, Michael J. ;

Alvarez, Sophie ;

Feinberg, Mark W. ;

Sun, Xinghui .

NUCLEIC ACIDS RESEARCH, 2019, 47 (03) :1505-1522

[3] From basic apoptosis discoveries to advanced selective BCL-2 family inhibitors [J].

Ashkenazi, Avi ;

Fairbrother, Wayne J. ;

Leverson, Joel D. ;

Souers, Andrew J. .

NATURE REVIEWS DRUG DISCOVERY, 2017, 16 (04) :273-284

[4] Thirty years of BCL-2: translating cell death discoveries into novel cancer therapies [J].

Delbridge, Alex R. D. ;

Grabow, Stephanie ;

Strasser, Andreas ;

Vaux, David L. .

NATURE REVIEWS CANCER, 2016, 16 (02) :99-109

[5] Lack of Immunomodulatory Interleukin-27 Enhances Oncogenic Properties of Mutant p53 In Vivo [J].

Dibra, Denada ;

Mitra, Abhisek ;

Newman, Melisa ;

Xia, Xueqing ;

Cutrera, Jeffry J. ;

Gagea, Mihai ;

Kleinerman, Eugenie S. ;

Lozano, Guillermina ;

Li, Shulin .

CLINICAL CANCER RESEARCH, 2016, 22 (15) :3876-3883

[6]

Duffy MJ, 2020, SEMIN CANC BIOL, DOI [10.1016/j.semcancer.2020.07.00546, DOI 10.1016/J.SEMCANCER.2020.07.00546]

[7] Cancer and Leukemia Group B 90203 (Alliance): Radical Prostatectomy With or Without Neoadjuvant Chemohormonal Therapy in Localized, High-Risk Prostate Cancer [J].

Eastham, James A. ;

Heller, Glenn ;

Halabi, Susan ;

Monk, J. Paul ;

Beltran, Himisha ;

Gleave, Martin ;

Evans, Christopher P. ;

Clinton, Steven K. ;

Szmulewitz, Russell Z. ;

Coleman, Jonathan ;

Hillman, David W. ;

Watt, Colleen R. ;

George, Saby ;

Sanda, Martin G. ;

Hahn, Olwen M. ;

Taplin, Mary-Ellen ;

Parsons, J. Kellogg ;

Mohler, James L. ;

Small, Eric J. ;

Morris, Michael J. .

JOURNAL OF CLINICAL ONCOLOGY, 2020, 38 (26) :3042-3050

[8] Ki67 Proliferation Index as a Tool for Chemotherapy Decisions During and After Neoadjuvant Aromatase Inhibitor Treatment of Breast Cancer: Results From the American College of Surgeons Oncology Group Z1031 Trial (Alliance) [J].

Ellis, Matthew J. ;

Suman, Vera J. ;

Hoog, Jeremy ;

Goncalves, Rodrigo ;

Sanati, Souzan ;

Creighton, Chad J. ;

DeSchryver, Katherine ;

Crouch, Erika ;

Brink, Amy ;

Watson, Mark ;

Luo, Jingqin ;

Tao, Yu ;

Barnes, Michael ;

Dowsett, Mitchell ;

Budd, G. Thomas ;

Winer, Eric ;

Silverman, Paula ;

Esserman, Laura ;

Carey, Lisa ;

Ma, Cynthia X. ;

Unzeitig, Gary ;

Pluard, Timothy ;

Whitworth, Pat ;

Babiera, Gildy ;

Guenther, J. Michael ;

Dayao, Zoneddy ;

Ota, David ;

Leitch, Marilyn ;

Olson, John A., Jr. ;

Allred, D. Craig ;

Hunt, Kelly .

JOURNAL OF CLINICAL ONCOLOGY, 2017, 35 (10) :1061-+

[9] Intra/Extracellular Lactic Acid Exhaustion for Synergistic Metabolic Therapy and Immunotherapy of Tumors [J].

Gao, Fan ;

Tang, Ying ;

Liu, Wen-Long ;

Zou, Mei-Zhen ;

Huang, Cui ;

Liu, Chuan-Jun ;

Zhang, Xian-Zheng .

ADVANCED MATERIALS, 2019, 31 (51)

[10] THE BCL-2 FAMILY SAGA [J].

Garcia-Saez, Ana J. .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2020, 21 (10) :565-+

← 1 2 3 4 5 →