26 research outputs found
Vitamin C supramolecular hydrogel for enhanced cancer immunotherapy
Vitamin C (VitC) has shown great promise to promote cancer immunotherapy, however, its high hydrophilicity makes it quickly excreted, leading to limited therapeutic efficiency even with frequent high-dose administration. Herein, we provide a pioneering report about the employment of VitC amphiphile self-assembled nanofiber hydrogels for enhanced cancer immunotherapy. Specifically, driven by hydrogen bonding and hydrophobic interactions, the synthesized VitC amphiphile, consisting of a hydrophilic VitC headgroup and a hydrophobic alkyl chain, could self-assemble into an injectable nanofiber hydrogel with self-healing properties. The formed VitC hydrogel not only serves as a reservoir for VitC but also acts as an effective delivery platform for stimulator of interferon genes (STING) agonist-4 (SA). Interestingly, the VitC hydrogel itself exhibits antitumor effects by upregulating genes related to interferon (IFN) signaling, apoptotic signaling and viral recognition and defense. Moreover, the SA-encapsulated VitC hydrogel (SA@VitC hydrogel) synergistically activated the immune system to inhibit the progression of both local and abscopal tumors
Smart Asymmetric Vesicles with Triggered Availability of Inner Cell-Penetrating Shells for Specific Intracellular Drug Delivery
Smart nanocarriers
attract considerable interest in the filed of precision nanomedicine.
Dynamic control of the interaction between nanocarriers and cells
offers the feasibility that in situ activates cellular internalization
at the targeting sites. Herein, we demonstrate a novel class of enzyme-responsive
asymmetric polymeric vesicles self-assembled from matrix metalloproteinase
(MMP)-cleavable peptide-linked triblock copolymer, polyÂ(ethylene glycol)-<i>GPLGVRG</i>-<i>b</i>-polyÂ(ε-caprolactone)-<i>b</i>-polyÂ(3-guanidinopropyl methacrylamide) (PEG-<i>GPLGVRG</i>-PCL-PGPMA), in which the cell-penetrating PGPMA segments asymmetrically
distribute in the outer and inner shells with fractions of 9% and
91%, respectively. Upon treatment with MMP-2 to cleave the stealthy
PEG shell, the vesicles undergo morphological transformation into
fused multicavity vesicles and small nanoparticles, accompanied by
redistribution of PGPMA segments with 76% exposed to the outside.
The vesicles after dePEGylation show significantly increased cellular
internalization efficiency (∼10 times) as compared to the original
ones due to the triggered availability of cell-penetrating shells.
The vesicles loading hydrophobic anticancer drug paclitaxel (PTX)
in the membrane exhibit significantly enhanced cytotoxicity against
MMP-overexpressing HT1080 cells and multicellular spheroids. The proposed
vesicular system can serve as a smart nanoplatform for in situ activating
intracellular drug delivery in MMP-enriched tumors