8 research outputs found
Redox-Responsive Heparin-Chlorambucil Conjugate Polymeric Prodrug for Improved Anti-Tumor Activity
Polymeric prodrug-based delivery systems have been extensively studied to find a better solution for the limitations of a single drug and to improve the therapeutic and pharmacodynamics properties of chemotherapeutic agents, which can lead to efficient therapy. In this study, redox-responsive disulfide bond-containing amphiphilic heparin-chlorambucil conjugated polymeric prodrugs were designed and synthesized to enhance anti-tumor activities of chlorambucil. The conjugated prodrug could be self-assembled to form spherical vesicles with 61.33% chlorambucil grafting efficiency. The cell viability test results showed that the prodrug was biocompatible with normal cells (HaCaT) and that it selectively killed tumor cells (HeLa cells). The uptake of prodrugs by HeLa cells increased with time. Therefore, the designed prodrugs can be a better alternative as delivery vehicles for the chlorambucil controlled release in cancer cells
Bioinspired, Manganese-Chelated Alginate–Polydopamine Nanomaterials for Efficient in Vivo <i>T</i><sub>1</sub>‑Weighted Magnetic Resonance Imaging
Manganese-based
nanomaterials are an emerging new class of magnetic
resonance imaging (MRI) contrast agents (CAs) that provide impressive
contrast abilities. MRI CAs that can respond to pathophysiological
parameters such as pH or redox potential are also highly in demand
for MRI-guided tumor diagnosis. Until now, synthesizing nanomaterials
with good biocompatibility, physiochemical stability, and good contrast
effects remains a challenge. This study investigated two new systems
of calcium/manganese cations complexed with either alginate–polydopamine
or alginate–dopamine nanogels [AlgPDA(Ca/Mn) NG or AlgDA(Ca/Mn)
NG]. Under such systems, Ca cations form ionic interactions via carboxylic
acids of the Alg backbone to enhance the stability of the synthetic
nanogels (NGs). Likewise, complexation of Mn cations also increased
the colloidal stability of the synthetic NGs. The magnetic property
of the prepared CAs was confirmed with superconducting quantum interference
device measurements, proving the potential paramagnetic property.
Hence, the <i>T</i><sub>1</sub> relaxivity measurement showed
that PDA-complexed synthetic NGs reveal a strong positive contrast
enhancement with <i>r</i><sub>1</sub> = 12.54 mM<sup>–1</sup>·s<sup>–1</sup> in 7.0 T MRI images, whereas DA-complexed
synthetic NGs showed a relatively lower <i>T</i><sub>1</sub> relaxivity effect with <i>r</i><sub>1</sub> = 10.13 mM<sup>–1</sup>·s<sup>–1</sup>. In addition, both the
synthetic NGs exhibit negligible cytotoxicity with >92% cell viability
up to 0.25 mM concentration, when incubated with the mouse macrophage
(RAW 264.7) and HeLa cells, and high biocompatibility under in vivo
analysis. The in vivo MRI test indicates that the synthetic NG exhibits
a high signal-to-noise ratio for longer hours, which provides a longer
image acquisition time for tumor and anatomical imaging. Furthermore, <i>T</i><sub>1</sub>-weighted MRI results revealed that PEGylated
AlgPDA(Ca/Mn) NGs significantly enhanced the signals from liver and
tumor tissues. Therefore, owing to the enhanced permeability and retention
effect, significantly enhanced in vitro and in vivo imagings, low
cost, and one-pot synthesis method, the Mn-based biomimetic approach
used in this study provides a promising and competitive alternative
for noninvasive tumor detection and comprehensive anatomical diagnosis
Biotin-Decorated PAMAM G4.5 Dendrimer Nanoparticles to Enhance the Delivery, Anti-Proliferative, and Apoptotic Effects of Chemotherapeutic Drug in Cancer Cells
Biotin receptors are overexpressed by various types of solid cancer cells and play a significant role in tumor metabolism, growth, and metastasis. Thus, targeting the biotin receptors on tumor cells may enhance the efficiency and reduce the side-effects of chemotherapy. The aim of this study was to develop a biotin-coupled poly(amido)amine (PAMAM) (PG4.5) dendrimer nanoparticle to enhance the tumor-specific delivery and intracellular uptake of anticancer drugs via receptor-mediated endocytosis. We modified PG4.5 with diethylenetriamine (DETA) followed by biotin via an amide bond and characterized the resulting PG4.5-DETA-biotin nanoparticles by 1H NMR, FTIR, and Raman spectroscopy. Loading and releasing of gemcitabine (GEM) from PG4.5-DETA-biotin were evaluated by UV–Visible spectrophotometry. Cell viability and cellular uptake were examined by MTT assay and flow cytometry to assess the biocompatibility, cellular internalization efficiency and antiproliferative activity of PG4.5-DETA-biotin/GEM. Gemcitabine-loaded PG4.5-DETA-biotin nanoparticles were spherical with a particle size of 81.6 ± 6.08 nm and zeta potential of 0.47 ± 1.25 mV. Maximum drug-loading content and encapsulation efficiency were 10.84 ± 0.16% and 47.01 ± 0.71%, respectively. Nearly 60.54 ± 1.99% and 73.96 ± 1.14% of gemcitabine was released from PG4.5-DETA-biotin/GEM nanoparticles after 48 h at the acidic pH values of 6.5 and 5, respectively. Flow cytometry and fluorescence microscopy of cellular uptake results revealed PG4.5-DETA-biotin/GEM nanoparticles selectively targeted cancer cells in vitro. Cytotoxicity assays demonstrated gemcitabine-loaded PG4.5-DETA-biotin significantly reduced cell viability and induced apoptosis in HeLa cells. Thus, biotin-coupled PG4.5-DETA nanocarrier could provide an effective, targeted drug delivery system and selectively convey gemcitabine into tumor cells
Ibuprofen-Loaded Heparin Modified Thermosensitive Hydrogel for Inhibiting Excessive Inflammation and Promoting Wound Healing
Hydrogels have been investigated as ideal biomaterials for wound treatment owing to their ability to form a highly moist environment which accelerates cell migration and tissue regeneration for prompt wound healing. They can also be used as a drug carrier for local delivery, and are able to activate immune cells to enhance wound healing. Here, we developed heparin-conjugated poly(N-isopropylacrylamide), an injectable, in situ gel-forming polymer, and evaluated its use in wound healing. Ibuprofen was encapsulated into the hydrogel to help reduce pain and excessive inflammation during healing. In addition to in vitro studies, a BALB/c mice model was used to evaluate its effect on would healing and the secretion of inflammatory mediators. The in vitro assay confirmed that the ibuprofen released from the hydrogel dramatically reduced lipopolysaccharide-induced inflammation by suppressing the production of NO, PGE2 and TNF-α in RAW264.7 macrophages. Moreover, an in vivo wound healing assay was conducted by applying hydrogels to wounds on the backs of mice. The results showed that the ibuprofen-loaded hydrogel improved healing relative to the phosphate buffered saline group. This study indicates that ibuprofen loaded in an injectable hydrogel is a promising candidate for wound healing therapy