Abstract
Triple negative breast cancer (TNBC) metastasis is still one of the obstacles in clinical treatment, while highly-effective cancer drugs usually cannot be used for their hydrophobicity and comprehensive system toxicity. This study built a kind of pH-sensitive nanoparticles (PP/H NPs) constructed by poly (lactic-co-glycolic acid) modified with β-cyclodextrin (PLGA-β-CD), polyethyleneimine grafted with benzimidazole (PEI-BM) and low molecular weight heparin (LMWH) to delivery Celastrol (Cela) and ferrocene (Fc) for breast cancer therapy. PLGA-β-CD and PEI-BM were synthesized by amidation reaction, the amphipathic polymer nanoparticles with 108.37 ± 1.02 nm were self-assembled in water. After PP/H NPs treatment, the half maximal inhibitory concentration (IC50) decreased by 91% compared with Cela, and ROS level was also elevated. PP/H NPs led to substantial tumor inhibiting rate (TIR, 65.86%), utilized LMWH to strengthen the anti-metastasis effect of PP/H NPs. PP/H NPs took advantage of exogenous chemotherapeutics and endogenous ROS to inhibit tumor growth, and combined with LMWH to hinder breast cancer metastasis.
Keywords:
Celastrol; LMWH; pH-Responsive nanoparticles.
Copyright © 2021. Published by Elsevier B.V.
MeSH terms
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Animals
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Benzimidazoles / chemistry
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Cell Line, Tumor
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Cell Movement / drug effects
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Cell Survival / drug effects
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Delayed-Action Preparations
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Drug Carriers*
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Drug Compounding
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Female
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Ferrous Compounds / chemistry
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Ferrous Compounds / pharmacology*
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Heparin, Low-Molecular-Weight / chemistry*
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Hydrogen-Ion Concentration
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Metallocenes / chemistry
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Metallocenes / pharmacology*
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Mice
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Mice, Inbred BALB C
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Nanoparticles*
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Neoplasm Invasiveness
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Pentacyclic Triterpenes / chemistry
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Pentacyclic Triterpenes / pharmacology*
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Polyethyleneimine / chemistry
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Polylactic Acid-Polyglycolic Acid Copolymer / chemistry
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Reactive Oxygen Species / metabolism
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Stimuli Responsive Polymers / chemistry*
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Triple Negative Breast Neoplasms / drug therapy*
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Triple Negative Breast Neoplasms / metabolism
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Triple Negative Breast Neoplasms / pathology
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Tumor Burden / drug effects
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beta-Cyclodextrins / chemistry
Substances
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Antineoplastic Agents
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Benzimidazoles
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Delayed-Action Preparations
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Drug Carriers
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Ferrous Compounds
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Heparin, Low-Molecular-Weight
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Metallocenes
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Pentacyclic Triterpenes
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Reactive Oxygen Species
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Stimuli Responsive Polymers
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beta-Cyclodextrins
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Polylactic Acid-Polyglycolic Acid Copolymer
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Polyethyleneimine
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benzimidazole
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celastrol
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ferrocene