Hyaluronic acid-coated and Olaparib-loaded PEI - PLGA nanoparticles for the targeted therapy of triple negative breast cancer.

Huiping Hu, Yu Zhang, Wenting Ji, Hao Mei, Tingting Wu, Zihao He, Kaiping Wang, Chen Shi
Author Information
  1. Huiping Hu: Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China.
  2. Yu Zhang: Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China.
  3. Wenting Ji: Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China.
  4. Hao Mei: Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China.
  5. Tingting Wu: Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China.
  6. Zihao He: Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China.
  7. Kaiping Wang: Hubei Key Laboratory of Nature Medicinal Chemistry and Resource Evaluation, Tongji Medical College of Pharmacy, Huazhong University of Science and Technology, Wuhan, P. R. China.
  8. Chen Shi: Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China.

Abstract

AIM: To prepare the hyaluronic acid-coated Olaparib-loaded PEI - PLGA nanoparticles (HA-Ola-PPNPs) and investigate their tumour-targeted anticancer effect.
METHODS: The synthesis of HA-Ola-PPNPs was verified by DLS, TEM and SEM, followed was measured its cytotoxicity using CCK-8 assay. Confocal microscopy was used to observe the cellular uptake. Cell apoptosis was analysed by flow cytometry, biological SEM, and TEM. The expression of related proteins within the tumour site was investigated by immunostaining.
RESULTS: The prepared HA-Ola-PPNPs showed a diameter of ∼160 nm with a negatively charged surface (-16.9 ± 2.7 mV) and sustained drug release behaviour. And the encapsulation efficiency of HA-Ola-PPNPs was 78.63 ± 5.29%. HA-Ola-PPNPs exhibited efficient and antitumor activities. HA-Ola-PPNPs induced cell apoptosis by upregulating Bax, Cytochrome C, and Caspase 3, downregulating Bcl-2 in breast cancer-bearing mice.
CONCLUSIONS: According to the results, the Ola-loaded and HA-coated PEI - PLGA nanoparticles could be considered as a powerful tumour-targeted drug delivery system for TNBC treatment.

Keywords

MeSH Term

Animals
Cell Line, Tumor
Drug Carriers
Humans
Hyaluronic Acid
Mice
Nanoparticles
Phthalazines
Piperazines
Triple Negative Breast Neoplasms

Chemicals

Drug Carriers
Phthalazines
Piperazines
Hyaluronic Acid
olaparib

Word Cloud

Created with Highcharts 10.0.0HA-Ola-PPNPsnanoparticlesPEI - PLGAhyaluronicacid-coatedOlaparib-loadedtumour-targetedTEMSEMapoptosisdrugbreastdeliverysystemTNBCAIM:prepareinvestigateanticancereffectMETHODS:synthesisverifiedDLSfollowedmeasuredcytotoxicityusingCCK-8assayConfocalmicroscopyusedobservecellularuptakeCellanalysedflowcytometrybiologicalexpressionrelatedproteinswithintumoursiteinvestigatedimmunostainingRESULTS:preparedshoweddiameter∼160 nmnegativelychargedsurface-169 ± 27 mVsustainedreleasebehaviourencapsulationefficiency7863 ± 529%exhibitedefficientantitumoractivitiesinducedcellupregulatingBaxCytochromeCCaspase3downregulatingBcl-2cancer-bearingmiceCONCLUSIONS:AccordingresultsOla-loadedHA-coatedconsideredpowerfultreatmentHyaluronictargetedtherapytriplenegativecancerOlaparibPEI-PLGATargetedacid

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