Evodiamine
(EVO) and Berberine (BBR), from Euodiae Fructus and Coptidis rhizoma, have been used as an herbal medicine pair
in traditional Chinese medicine to exert synergistic antitumor effects
against various types of tumor cells. However, their clinical use
is limited by their poor solubility and adverse toxic side effects.
Mesoporous silica nanoparticles (MSNs) possess excellent properties
such as a readily functionalized surface, prominent biocompatibility,
and huge specific surface area for loading with hydrophobic and hydrophilic
drug. On this basis, a novel temperature- and pH-responsive dual drug
delivery platform has been developed, in which lipid-coated MSN@p(NIPAM-co-MA) codelivers EVO and BBR. The results indicate that
the nanocarrier improves the efficacy and biocompatibility of the
drug pair and maintain desirable drug profiles at the low pH and higher
temperature of the tumor microenvironment. The dual drug-loaded MSNs
showed excellent synergistic therapy effects in vitro (cytotoxicity, cell migration and invasion, angiogenesis) and in vivo (growth of tumor grafts in mice). Meanwhile, the
dual drug-loaded nanoparticles showed lower systemic toxicity than
either drug alone, the free drug combination, or Taxol. These results
suggest that the temperature- and pH-sensitive lipid-coated MSNs are
a promising novel carrier for both hydrophobic and hydrophilic drugs.
In this research, KLA-modified liposomes co-loaded with 5-fluorouracil and paclitaxel (KLA-5-FU/PTX Lps) were developed, and their antitumor activity against triple-negative breast cancer (TNBC) was evaluated. KLA-5-FU/PTX Lps were prepared using the thin-film dispersion method, and their in vitro anticancer efficacy was assessed in human breast cancer cells (MDA-MB-231). An MDA-MB-231 tumor-bearing mouse model was also established to evaluate their antitumor efficacy in vivo. KLA-5-FU/PTX Lps showed enhanced cytotoxicity against MDA-MB-231 cells, improved drug delivery to mitochondria, and induced mitochondria-mediated apoptosis. The modified liposomes also showed favorable antitumor activity in vivo due to their strong ability to target tumors and mitochondria. The liposomes showed no obvious systemic toxicity. Our results suggest that KLA-5-FU/PTX Lps are a promising system with which to target the delivery of antitumor drugs to mitochondria as a treatment for TNBC.
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