Treatment of cancer metastasized to bone is still a challenge due to hydrophobicity, instability, and lack of target specificity of anticancer drugs. Poly (ethylene glycol)-poly (ε-caprolactone) polymer (PEG-PCL) is an effective, biodegradable, and biocompatible hydrophobic drug carrier, but lacks bone specificity. Polyaspartic acid with eight peptide sequences, that is, (Asp)
8
, has a strong affinity to bone surface. The aim of this study was to synthesize (Asp)
8
-PEG-PCL nanoparticles as a bone-specific carrier of hydrophobic drugs to treat cancer metastasized to bone.
1
H nuclear magnetic resonance, Fourier transform infrared spectroscopy, and transmission electron microscopy data showed that (Asp)
8
-PEG-PCL nanoparticles (size 100 nm) were synthesized successfully. (Asp)
8
-PEG-PCL nanoparticles did not promote erythrocyte aggregation. Fluorescence microscopy showed clear uptake of Nile red-loaded (Asp)
8
-PEG-PCL nanoparticles by cancer cells. (Asp)
8
-PEG-PCL nanoparticles did not show cytotoxic effect on MG63 and human umbilical vein endothelial cells at the concentration of 10–800 μg/mL. (Asp)
8
-PEG-PCL nanoparticles bound with hydroxyapatite 2-fold more than PEG-PCL. Intravenously injected (Asp)
8
-PEG-PCL nanoparticles accumulated 2.7-fold more on mice tibial bone, in comparison to PEG-PCL. Curcumin is a hydrophobic anticancer drug with bone anabolic properties. Curcumin was loaded in the (Asp)
8
-PEG-PCL. (Asp)
8
-PEG-PCL showed 11.07% loading capacity and 95.91% encapsulation efficiency of curcumin. The curcumin-loaded (Asp)
8
-PEG-PCL nanoparticles gave sustained release of curcumin in high dose for >8 days. The curcumin-loaded (Asp)
8
-PEG-PCL nanoparticles showed strong antitumorigenic effect on MG63, MCF7, and HeLa cancer cells. In conclusion, (Asp)
8
-PEG-PCL nanoparticles were biocompatible, permeable in cells, a potent carrier, and an efficient releaser of hydrophobic anticancer drug and were bone specific. The curcumin-loaded (Asp)
8
-PEG-PCL nanoparticles showed strong antitumorigenic ability in vitro. Therefore, (Asp)
8
-PEG-PCL nanoparticles could be a potent carrier of hydrophobic anticancer drugs to treat the cancer metastasized to bone.
Abnormal activation of the gut mucosal immune system and a highly dysregulated gut microbiota play essential roles in the progression of inflammatory bowel disease (IBD). The clinical treatment of IBD remains highly challenging, with first‐line drugs showing limited efficacy and significant side effects. A reactive oxygen species (ROS)‐activated CO versatile nanomedicine (CMPs) capable of remodeling the gut immune‐microbiota microenvironment via potent anti‐oxidant, anti‐inflammatory, and antimicrobial effects is developed. CORM‐401‐loaded mannose‐modified peptide dendrimer nanogel: CMPs preferentially congregate on the surface of damaged colon mucosa after rectal administration and are subsequently internalized by activated immune cells. CORM‐401 can release numerous CO molecules in response to high ROS levels in cells and at the site of IBD, resulting in multiple therapeutic effects. In vitro and in vivo studies have demonstrated that CMPs scavenge ROS, suppress inflammatory responses, eliminate pathogens, and alleviate colitis in mouse models. RNA sequencing reveals that CMPs successfully remodel gut mucosal immune homeostasis by scavenging ROS, inhibiting NF‐κB/p38MAPK, activating PI3K‐Akt, and inhibiting HIF‐1‐induced glycolysis. 16S ribosomal RNA sequencing shows that CMPs can remodel the gut flora composition by restraining detrimental bacteria and augmenting beneficial bacteria. This study develops a promising and versatile nanomedicine for the management of IBD.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.