Contruction of Drug Delivery System of Cancer Cell Membrane Coated Nanoparticles and Application in Breast Cancer
ZHANG Liu-yuan1, GAO Chun-xiao2, XIA Gui-min3, YAN De-yue4, CHEN Lian-zhen5, YUAN Wei1*, MA Jie2
1. National Cancer Center / National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College State Key Laboratory of Molecular Oncology, Beijing 100021, China; 2. Beijing Hospital Biotherapy Center / National Gerontology Center, Beijing 100730, China; 3. Preparation Room, Institute of Medical Biotechnology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100050, China; 4. State Key Laboratory of Metal Matrix Composites, School of Chemistry and Chemical Engineering, Shanghai Jiaotong University, Shanghai 200240, China; 5. National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Pharmacy Department,Beijing 100021, China
Abstract：OBJECTIVE To investigate a biomimetic nano-targeted drug modifide by cancer cell membrane and to discuss its efficiency in breast cancer. METHODS The lac-DOX/DOX was prepared by filming-rehydration method, and the 4T1 cell membrane was extracted at the same time. The lac-DOX /DOX@4T1m was prepared by sonication method.. The morphology of lac-DOX /DOX@4T1m was observed by a transmission electron microscopy. The protein on 4T1 cell membrane was analyzed by gel electrophoresis. The targeting of drugs to homologous cancer cells in vivo and in vitro were evaluated by cell uptake experiments and imaging experiments of small animals. 4T1 tumor-bearing Balb/c mice were built, the anti-tumor efficacy and biosafety of lac-DOX/ DOX@4t1m were evaluated . RESULTS The prepared lac-DOX /DOX@4T1m have a regular spherical shape with an average particle diameter of (204.8±13.0)nm, and the protein entirety remained on the cell membrane. The results of cell uptake experiments and in vivo imaging experiments of mice showed that lac-DOX/DOX@4T1m can target 4T1 cells. Antitumor test results showed that lac-DOX/ DOX@4T1m could inhibit tumor growth more effectively and significantly reduce the damage to liver function. CONCLUSION In this study, a bionic nano-drug is successfully prepared, which improve the tumor targeting and therapeutic effect, reduce the toxic effects of adriamycin, and improve the drug safety.
张刘源, 高春晓, 夏桂民, 颜德岳, 陈莲珍, 袁伟, 马洁. 癌细胞膜修饰纳米载药体系的构建及其在乳腺癌治疗中的应用[J]. 中国药学杂志, 2020, 55(13): 1086-1093.
ZHANG Liu-yuan, GAO Chun-xiao, XIA Gui-min, YAN De-yue, CHEN Lian-zhen, YUAN Wei, MA Jie. Contruction of Drug Delivery System of Cancer Cell Membrane Coated Nanoparticles and Application in Breast Cancer. Chinese Pharmaceutical Journal, 2020, 55(13): 1086-1093.
SHAH S N, COPE L, POH W, et al. HMGA1:a master regulator of tumor progression in triple-negative breast cancer cells[J]. PLoS One, 2013, 8(5):e63419.
[2]
FAN L, STRASSER-WEIPPL K, ST LOUIS J, et al. Breast cancer in China[J]. Lancet Oncol,2014, 5(7):279-289.
[3]
JENNIFER C R. Cancer cancer immunotherapy[J]. Science, 2013, 342(6165):1432-1433.
[4]
XU Y,LUO Y,WANG Z Y, et al. MRTF-A can activate Nrf2 to increase the resistance to doxorubicin[J]. Oncotarget, 2017, 8(5):8436-8446.
[5]
CHU C Y,JIN Y T,ZHANG W, et al. CAIX is upregulated in CoCl 2-induced hypoxia and associated with cell invasive potential and a poor prognosis of breast cancer[J]. Int J Oncol,2016,48 (1):271-280.
[6]
HORN C F, OSHIYO C, MARSH S, et al. Doxorubicin pathways:pharmacodynamics and adverse effects[J]. Pharmacogenet Genomics,2011,21(7):440-446.
[7]
MOHEBBATI R, SHAFEI M N, SOUKHTANLOO M, et al. Adriamycin-induced oxidative stress is prevented by mixed hydro-alcoholic extract of nigella sativa and curcuma longain rat kidney[J]. Avicenna J Phytomed,2016,6(1):86-94.
[8]
CREMERS H F M,VERRIJK R,NOTEBORN H P J M, et al. Adriamycin loading and release characteristics of albumin-heparin conjugate microspheres[J]. J Controlled Release,2017,29(1-2):143-155.
[9]
ZHANG C Y, PAN D Y, LUO K, et al. Peptide dendrimer-doxorubicin conjugate-based nanoparticles as an enzyme-responsive drug delivery systerm for cancer therapy[J]. Adv Healthcare Mater, 2014, 3(8):1299-1308.
[10]
MOU Q B, MA Y, ZHU X Y, et al. A small molecule nanodrug consisting of amphiphilic targeting ligand-chemotherapy drug conjugate for targeted cancer therapy[J]. J Controlled Release, 2016, 230:34-44.
[11]
DENG G, SUN Z, LI S, et al. Cell-membrane immunotherapy based on natural killer cell membrane coated nanoparticles for the effective inhibition of primary and abscopal tumor growth[J]. ACS Nano, 2018, 12:12096-12108.
[12]
YING M, ZHUANG J, WEI X K, et al. Remote-loaded platelet vesicles for disease-targeted delivery of therapeutics[J]. Adv Funct Mater, 2018,28(22):1801032.
[13]
CAO H Q, DAN Z L, HE X Y, et al. Liposomes coated with isolated macrophage membrane can target lung metastasis of breast cancer[J]. ACS Nano, 2016, 10:7738-7748.
[14]
PORAND C D, AMLEIDA PORAND G. Mesenchymal stem cells as therapeutics and vehicles for gene and drug delivery[J]. Adv Drug Deliv Rev, 2010, 62(12):1156-1166.
[15]
DIANA DEHAINI, WEI X L, RONNIE H, et al. Erythrocyte-platelet hybrid membrane coating for enhanced nanoparticle functionalization[J]. Adv Mater, 2017, 29(16):1-18.
[16]
SU J H, SUN H P, MENG Q S, et al. Long circulation red-blood-cell-mimetic nanoparticles with peptide-enhanced tumor penetration for simultaneously inhibiting growth and lung metastasis of breast cancer[J]. Adv Funct Mater, 2016, 26:1243-1252.
[17]
SUN H, SU J, MENG Q, et al. Cancer-cell-biomimetic nanoparticles for targeted therapy of homotypic tumors[J]. Adv Mater, 2016, 28(43):9581-9588.
[18]
ZHU J Y, ZHENG D W, ZHANG M K, et al. Preferential cancer cell self-recognition and tumor self-targeting by coating nanoparticles with homotypic cancer cell membranes[J]. Nano Lett, 2016, 16(9):5895-5901.
[19]
ZHAO X Z. Cancer cell membrane-coated upconversion nanoprobes for highly specific tumor imaging[J]. Adv Mater, 2016, 28:3460-3466.
[20]
HU C M J, ZHANG L, SANTOSH A, et al. Erythrocyte membrane-camouflaged polymeric nanoparticles as a biomimetic delivery platform[J]. PNAS, 2011, 108(27):10980-10985.
[21]
FIDLER I J. The relationship of embolic homogeneity, number, size and viability to the incidence of experimental metastasis[J]. Eur J Cancer, 1975, 9:223-227.
2020, Vol. 55 
