Antioxidant, Enzyme, and H 2 O 2 -Triggered Melanoma Targeted Mesoporous Organo-Silica Nanocomposites for Synergistic Cancer Therapy.
Hyung Woo ChoiJae Hyun LimTaewook KangBong Geun ChungPublished in: Antioxidants (Basel, Switzerland) (2022)
The multi-stimuli responsive drug delivery system has recently attracted attention in cancer treatments, since it can reduce several side effects and enhance cancer therapeutic efficacy. Herein, we present the intracellular antioxidant (glutathione, GSH), enzyme (hyaluronidase, HAase), and hydrogen peroxide (H 2 O 2 ) triggered mesoporous organo-silica (MOS) nanocomposites for multi-modal treatments via chemo-, photothermal, and photodynamic cancer therapies. A MOS nanoparticle was synthesized by two-types of precursors, tetraethyl orthosilicate (TEOS) and bis[3-(triethoxysilyl)propyl] tetrasulfide (BTES), providing large-sized mesopores and disulfide bonds cleavable by GSH. Additionally, we introduced a new β -cyclodextrin-hyaluronic acid (CDHA) gatekeeper system, enabling nanocomposites to form the specific interaction with the ferrocene (Fc) molecule, control the drug release by the HAase and H 2 O 2 environment, as well as provide the targeting ability against the CD44-overexpressing melanoma (B16F10) cells. Indocyanine green (ICG) and doxorubicin (Dox) were loaded in the MOS-Fc-CDHA (ID@MOS-Fc-CDHA) nanocomposites, allowing for hyperthermia and cytotoxic reactive oxygen species (ROS) under an 808 nm NIR laser irradiation. Therefore, we demonstrated that the ID@MOS-Fc-CDHA nanocomposites were internalized to the B16F10 cells via the CD44 receptor-mediated endocytosis, showing the controlled drug release by GSH, HAase, and H 2 O 2 to enhance the cancer therapeutic efficacy via the synergistic chemo-, photothermal, and photodynamic therapy effect.
Keyphrases
- cancer therapy
- drug delivery
- drug release
- photodynamic therapy
- reduced graphene oxide
- papillary thyroid
- hydrogen peroxide
- reactive oxygen species
- visible light
- hyaluronic acid
- quantum dots
- squamous cell
- induced apoptosis
- room temperature
- highly efficient
- carbon nanotubes
- cell cycle arrest
- childhood cancer
- nitric oxide
- gold nanoparticles
- fluorescent probe
- mass spectrometry
- lymph node metastasis
- young adults
- squamous cell carcinoma
- dna damage
- ionic liquid
- cell death
- high resolution
- signaling pathway
- transition metal
- cell proliferation