Background: Targeted cancer therapy has been extensively developed to improve the quality of treatment by reducing the systemic exposure of cytotoxic drug. Polymeric nanoparticles with conjugated targeting agents are widely investigated because they offer tunability in particle size, drug release profile and biocompatibility. Materials & methods: Here, we have prepared targeted multifunctional nanoparticles composed of a poly(lactic-co-glycolic acid) matrix, ZnS:Mn2+ quantum dots and camptothecin, and targeted them to EGF receptor overexpressing cells with a cetuximab antibody. Results: Physicochemical characterization of multifunctional nanoparticles showed stable particles with sizes of <200 nm. In vitro drug release and blood contact studies showed a sustained release profile, with limited hemolysis. In vitro cytotoxicity and cell uptake studies were carried out in A549, KB and MFC-7 cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, FACS, fluorescent microscopic images and spectroflourimetry. Conclusion: Our studies revealed higher camptothecin activity and uptake in cell lines that overexpress the EGF receptor. All these results suggest that anti-EGF receptor cetuximab-conjugated poly(lactic-co-glycolic acid) multifunctional nanoparticles can be used as a potential nanomedicine against cancer.
Epidermal growth factor receptor (EGFR), upregulated in gastric cancer patients, is an oncogene of interest in the development of targeted cancer nanomedicines. This study demonstrates in silico modeling of monoclonal antibody cetuximab (CET MAb)-conjugated docetaxel (DOCT)-loaded poly(γ-glutamic acid) (γ-PGA) nanoparticles (Nps) and evaluates the in vitro/in vivo effects on EGFR-overexpressing gastric cancer cells (MKN-28). Nontargeted DOCT-γ-PGA Nps (NT Nps: 110±40 nm) and targeted CET MAb-DOCT-γ-PGA Nps (T Nps: 200±20 nm) were prepared using ionic gelation followed by 1-Ethyl-3-(3-dimethyl aminopropyl)carbodiimide–N-Hydoxysuccinimide (EDC–NSH) chemistry. Increased uptake correlated with enhanced cytotoxicity induced by targeted Nps to EGFR +ve MKN-28 compared with nontargeted Nps as evident from MTT and flow cytometric assays. Nanoformulated DOCT showed a superior pharmacokinetic profile to that of free DOCT in Swiss albino mice, indicating the possibility of improved therapeutic effect in the disease model. Qualitative in vivo imaging showed early and enhanced tumor targeted accumulation of CET MAb-DOCT-γ-PGA Nps in EGFR +ve MKN-28–based gastric cancer xenograft, which exhibited efficient arrest of tumor growth compared with nontargeted Nps and free DOCT. Thus, actively targeted CET MAb-DOCT-γ-PGA Nps could be developed as a substitute to conventional nonspecific chemotherapy, and hence could become a feasible strategy for cancer therapy for EGFR-overexpressing gastric tumors.
The combination of desirable polymer properties and methods for synthesis, utilizing materials with various architectures, could be adopted for diverse clinical applications such as wound healing as well as stem cell differentiation. Natural polymers, particularly polysaccharides, are biocompatible and are reported to have structural similarities with extracellular matrix components. In this scenario, the present study fabricated a porous scaffold using a polysaccharide, galactoxyloglucan, isolated from Tamarind seed kernel, and studied its applications in stem cell attachment and wound healing. In-growth of human mesenchymal stem cells (hMSCs) presented a rounded morphology with increased proliferation. Scaffolds were surface-functionalized with silver nanoparticles to increase the antibacterial activity and the wound healing potential evaluated in preclinical mouse models. The current study provides an insight into how stem cells attach and grow in a naturally derived low-cost polysaccharide scaffold with antibacterial, biocompatible, and biodegradable properties.
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