Abstract：OBJECTIVE To synthesize the active-targeted olaparib-loaded polyethyleneimine-polyllactic-co-glycolic acid(PEI-PLGA) nanoparticles(HA-Ola-PPNPs) and investigate the therapy of triple negative breast cancer in vitro.METHODS The olaparib-loaded PEI-PLGA nanoparticles were prepared by the emulsion solvent diffusion evaporation method. And further modified with hyaluronic acid(HA) to prepare HA-Ola-PPNPs. The synthesis of HA-Ola-PPNPs was verified by dynamic light scattering(DLS) and transmission electron microscopy(TEM), the cytotoxicity was measured by CCK-8.Confocal microscopy was used to observe the uptake of NPs. Biological TEM was used to observe the morphological changes of cells and analyze the apoptosis.RESULTS The mean size of HA-Ola-PPNPs was (166.2±0.842)nm and showed negatively charged surface (-12.3±1.63)mV. The encapsulation efficiency of HA-Ola-PPNPs was (80.44±6.218)%. CCK-8 results showed that all the nanoparticles presented time-dependent and dose-dependent cytotoxicity, and HA-Ola-PPNPs exhibited efficient in vitro antitumor activities. The binding of HA to CD44 receptor could significantly improve the uptake of HA-Ola-PPNPs by MDA-MB-231 cells.And HA-Ola-PPNPs could effectively induce apoptosis of MDA-MB-231 cells.CONCLUSION In this study, active-targeted HA-Ola-PPNPs are successfully prepared, which could provide a new strategy for the clinical treatment of triple negative breast cancer(TNBC).
胡慧平, 汪汉香, 付之文, 刘金梅, 李石军, 张玉, 史琛. 主动靶向型载奥拉帕尼PEI-PLGA纳米粒的制备表征及抗三阴乳腺癌研究[J]. 中国药学杂志, 2022, 57(17): 1447-1452.
HU Hui-ping, WANG Han-xiang, FU Zhi-wen, LIU Jin-mei, LI Shi-jun, ZHANG Yu, SHI Chen. Preparation, Characterization and Anticancer Effect of Active-targeted Olaparib-loaded PEI-PLGA Nanoparticles. Chinese Pharmaceutical Journal, 2022, 57(17): 1447-1452.
ABRAMSON V G, LEHMANN B D, BALLINGER T J, et al. Subtyping of triple-negative breast cancer: implications for therapy[J]. Cancer, 2015, 121(1): 8-16.
[2]
JHAN J R, ANDRECHEK E R. Triple-negative breast cancer and the potential for targeted therapy[J]. Pharmacogenomics, 2017, 18(17): 1595-1609.
[3]
CAREY L, WINER E, VIALE G, et al. Triple-negative breast cancer: disease entity or title of convenience[J]. Nat Rev Clin Oncol, 2010, 7(12): 683-692.
[4]
JIN J, KRISHNAMACHARY B, MIRONCHIK Y, et al. Phototheranostics of CD44-positive cell populations in triple negative breast cancer[J]. Sci Rep, 2016, 6: 27871. Doi: 10.1038/srep27871.
[5]
PANESAR S, NEETHIRAJAN S. Microfluidics: rapid diagnosis for breast cancer[J]. Nano Micro Lett, 2016, 8(3): 204-220.
[6]
HENNEMAN L, VAN MILTENBURG M H, MICHALAK E M, et al. Selective resistance to the PARP inhibitor olaparib in a mouse model for BRCA1-deficient metaplastic breast cancer[J]. Proc Natl Acad Sci USA, 2015, 112(27): 8409-8414.
[7]
GELMON K A, TISCHKOWITZ M, MACKAY H, et al. Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study[J]. Lancet Oncol, 2011, 12(9): 852-861.
[8]
BUNDRED N, GARDOVSKIS J, JASKIEWICZ J, et al. Evaluation of the pharmacodynamics and pharmacokinetics of the PARP inhibitor olaparib: a phase I multicentre trial in patients scheduled for elective breast cancer surgery[J]. Invest New Drugs, 2013, 31(4): 949-958.
[9]
MATEO J, MORENO V, GUPTA A, et al. An adaptive study to determine the optimal dose of the tablet formulation of the PARP inhibitor olaparib[J]. Target Oncol, 2016, 11(3): 401-415.
[10]
MAZZUCCHELLI S, TRUFFI M, BACCARINI F, et al. H-Ferritin-nanocagedolaparib: a promising choice for both BRCA-mutated and sporadic triple negative breast cancer[J]. Sci Rep, 2017, 7(1): 7505.
[11]
SHI C, AHMAD K S, WANG K, et al. Improved delivery of the natural anticancer drug tetrandrine[J]. Int J Pharm, 2015, 479(1): 41-51.
[12]
HU F Q, LIU L N, DU Y Z, et al. Synthesis and antitumor activity of doxorubicin conjugated stearic acid-g-chitosan oligosaccharide polymeric micelles[J]. Biomaterials, 2009,30(36), 6955-6963.
[13]
PERACCHIA M T, GREF R, MINAMITAKE Y, et al. PEG-coated nanospheres from amphiphilic diblock and multiblock copolymers: Investigation of their drug encapsulation and release characteristics[J]. J Controlled Release, 1997,46(3): 223-231.
[14]
KELES H, NAYLOR A, CLEGG F, et al. Investigation of factors influencing the hydrolytic degradation of single PLGA microparticles[J]. Polym Degrad Stabil, 2015, 119: 228-241.Doi:10. 1016/j. polymdegradstab. 2015.04.025
[15]
ZHANG Y, CUI Z, MEI H, et al. Angelica sinensis polysaccharide nanoparticles as a targeted drug delivery system for enhanced therapy of liver cancer[J]. Carbohydr Polym, 2019, 219: 143-154. Doi: 10. 1016/j. carbpol. 2019.04.041
[16]
HUANG J, ZHANG H, YU Y, et al. Biodegradable self-assembled nanoparticles of poly(D,L-lactide-co-glycolide)/hyaluronic acid block copolymers for target delivery of docetaxel to breast cancer[J]. Biomaterials, 2014, 35(1): 550-566.
[17]
SHI C, ZENG F, FU D. Surfactant-free poly(lactide-co-glycolide) nanoparticles for improving in vitro anticancer efficacy of tetrandrine[J]. J Microencapsul, 2016, 33(3): 249-256.
[18]
EBRAHIMNEJAD P, DINARVAND R, SAJADI A, et al. Rad-Malekshahi, F. Atyabi, Preparation and in vitro evaluation of actively targetable nanoparticles for SN-38 delivery against HT-29 cell lines[J]. Nanomedicine, 2010, 6(3): 478-485.
2022, Vol. 57 
