4 research outputs found
Enzyme-responsive mannose-grafted magnetic nanoparticles for breast and liver cancer therapy and tumor-associated macrophage immunomodulation
Chemo-immunotherapy modifies the tumor microenvironment to enhance the immune response and improve chemotherapy. This study introduces a dual-armed chemo-immunotherapy strategy combating breast tumor progression while re-polarizing Tumor-Associated Macrophage (TAM) using prodigiosin-loaded mannan-coated magnetic nanoparticles (PG@M-MNPs). The physicochemical properties of one-step synthetized M-MNPs were analyzed, including X-ray diffraction, FTIR, DLS, VSM, TEM, zeta potential analysis, and drug loading content were carried out. Biocompatibility, cancer specificity, cellular uptake, and distribution of PG@M-MNPs were investigated using fluorescence and confocal laser scanning microscopy, and flow cytometry. Furthermore, the expression levels of IL-6 and ARG-1 after treatment with PG and PG@M-MNPs on M1 and M2 macrophage subsets were studied. The M-MNPs were successfully synthesized and characterized, demonstrating a size below 100 nm. The release kinetics of PG from M-MNPs showed sustained and controlled patterns, with enzyme-triggered release. Cytotoxicity assessments revealed an enhanced selectivity of PG@M-MNPs against cancer cells and minimal effects on normal cells. Additionally, immuno-modulatory activity demonstrates the potential of PG@M-MNPs to change the polarization dynamics of macrophages. These findings highlight the potential of a targeted approach to breast cancer treatment, offering new avenues for improved therapeutic outcomes and patient survival.</p
An Injectable Hydrogel Prepared Using a PEG/Vitamin E Copolymer Facilitating Aqueous-Driven Gelation
Hydrogels
have been widely explored for biomedical applications,
with injectable hydrogels being of particular interest for their ability
to precisely deliver drugs and cells to targets. Although these hydrogels
have demonstrated satisfactory properties in many cases, challenges
still remain for commercialization. In this paper, we describe a simple
injectable hydrogel based on poly(ethylene glycol) (PEG) and a vitamin
E (Ve) methacrylate copolymer prepared via simple free radical polymerization
and delivered in a solution of low molecular weight PEG and Ve as
the solvent instead of water. The hydrogel formed immediately in an
aqueous environment with a controllable gelation time. The driving
force for gelation is attributed to the self-assembly of hydrophobic
Ve residues upon exposure to water to form a physically cross-linked
polymer network via polymer chain rearrangement and subsequent phase
separation, a spontaneous process with water uptake. The hydrogels
can be customized to give the desired water content, mechanical strength,
and drug release kinetics simply by formulating the PEGMA-<i>co</i>-Ve polymer with an appropriate solvent mixture or by
varying the molecular weight of the polymer. The hydrogels exhibited
no significant cytotoxicity <i>in vitro</i> using fibroblasts
and good tissue compatibility in the eye and when injected subcutaneously.
These polymers thus have the potential to be used in a variety of
applications where injection of a drug or cell containing depot would
be desirable
Injectable and Degradable Poly(Oligoethylene glycol methacrylate) Hydrogels with Tunable Charge Densities as Adhesive Peptide-Free Cell Scaffolds
Injectable,
dual-responsive, and degradable poly(oligo ethylene
glycol methacrylate) (POEGMA) hydrogels are demonstrated to offer
potential for cell delivery. Charged groups were incorporated into
hydrazide and aldehyde-functionalized thermoresponsive POEGMA gel
precursor polymers via the copolymerization of N,<i>N</i>′-dimethylaminoethyl methacrylate (DMAEMA) or acrylic acid
(AA) to create dual-temperature/pH-responsive in situ gelling hydrogels
that can be injected via narrow gauge needles. The incorporation of
charge significantly broadens the swelling, degradation, and rheological
profiles achievable with injectable POEGMA hydrogels without significantly
increasing nonspecific protein adsorption or chronic inflammatory
responses following in vivo subcutaneous injection. However, significantly
different cell responses are observed upon charge incorporation, with
charged gels significantly improving 3T3 mouse fibroblast cell adhesion
in 2D and successfully delivering viable and proliferating ARPE-19
human retinal epithelial cells via an “all-synthetic”
matrix that does not require the incorporation of cell-adhesive peptides
“Click” Chemistry-Tethered Hyaluronic Acid-Based Contact Lens Coatings Improve Lens Wettability and Lower Protein Adsorption
Improving the wettability
of and reducing the protein adsorption to contact lenses may be beneficial
for improving wearer comfort. Herein, we describe a simple “click”
chemistry approach to surface functionalize poly(2-hydroxyethyl methacrylate)
(pHEMA)-based contact lenses with hyaluronic acid (HA), a carbohydrate
naturally contributing to the wettability of the native tear film.
A two-step preparation technique consisting of laccase/TEMPO-mediated
oxidation followed by covalent grafting of hydrazide-functionalized
HA via simple immersion resulted in a model lens surface that is significantly
more wettable, more water retentive, and less protein binding than
unmodified pHEMA while maintaining the favorable transparency, refractive,
and mechanical properties of a native lens. The dipping/coating method
we developed to covalently tether the HA wetting agent is simple,
readily scalable, and a highly efficient route for contact lens modification