Drug/Dye-Loaded, Multifunctional PEG–Chitosan–Iron Oxide Nanocomposites for Methotraxate Synergistically Self-Targeted Cancer Therapy and Dual Model Imaging
Abstract:Multifunctional nanocomposites hold great potential to integrate therapeutic and diagnostic functions into a single nanoscale structure. In this paper, we prepared the MTX-PEG-CS-IONPs-Cy5.5 nanocomposites by functionalizing the surface of chitosan-decorated iron oxide nanoparticles (CS-IONPs) with polyethylene glycolated methotraxate (MTX-PEG) and near-infrared fluorescent cyanin dye (Cy5.5). A clinically useful PEGylated anticancer prodrug, MTX-PEG, was also developed as a tumor cell-specific targeting ligan… Show more
“…4). Consistent with our previous study [25, 26], the result suggested that MTX-functionalized nanomulti-drug could specifically bind to FA receptors overexpressed on the surface of HeLa cells.Fig. 4
a CLSM images and b flow cytometry analysis of HeLa cells incubated with MTX-PEG-CPT NRs in the presence of excess of free FA, MTX-PEG-CPT NRs, and PEG-CPT NRs for 2 h. Cell nuclei are stained with PI.…”
We developed a novel self-targeted multi-drug co-delivery system based on rod-shaped 10-hydroxycamptothecin (CPT) nanoanticancer drug (CPT NRs) followed by a surface functionalization with self-targeting PEGylated lipid-conjugated methotrexate (MTX) pro-anticancer drug. The self-targeting effect and in vitro cell viability of the MTX-PEG-CPT NRs on HeLa cells were demonstrated by comparative cellular uptake and MTT assay of the PEG-CPT NRs. In vitro studies showed the feasibility of using this high drug-loading MTX-PEG-CPT NRs in self-targeted drug delivery, controlled-/sustained-release, and synergistic cancer therapy. More importantly, this work would stimulate interest in the use of PEGylated lipid-conjugated MTX by introducing an early-phase tumor-targeting role and then driving a late-phase anticancer role for the highly convergent design of nanomulti-drug, which may advantageously offer a new and simple strategy for simultaneously targeting and treating FA receptor-overexpressing cancer cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s11671-016-1599-y) contains supplementary material, which is available to authorized users.
“…4). Consistent with our previous study [25, 26], the result suggested that MTX-functionalized nanomulti-drug could specifically bind to FA receptors overexpressed on the surface of HeLa cells.Fig. 4
a CLSM images and b flow cytometry analysis of HeLa cells incubated with MTX-PEG-CPT NRs in the presence of excess of free FA, MTX-PEG-CPT NRs, and PEG-CPT NRs for 2 h. Cell nuclei are stained with PI.…”
We developed a novel self-targeted multi-drug co-delivery system based on rod-shaped 10-hydroxycamptothecin (CPT) nanoanticancer drug (CPT NRs) followed by a surface functionalization with self-targeting PEGylated lipid-conjugated methotrexate (MTX) pro-anticancer drug. The self-targeting effect and in vitro cell viability of the MTX-PEG-CPT NRs on HeLa cells were demonstrated by comparative cellular uptake and MTT assay of the PEG-CPT NRs. In vitro studies showed the feasibility of using this high drug-loading MTX-PEG-CPT NRs in self-targeted drug delivery, controlled-/sustained-release, and synergistic cancer therapy. More importantly, this work would stimulate interest in the use of PEGylated lipid-conjugated MTX by introducing an early-phase tumor-targeting role and then driving a late-phase anticancer role for the highly convergent design of nanomulti-drug, which may advantageously offer a new and simple strategy for simultaneously targeting and treating FA receptor-overexpressing cancer cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s11671-016-1599-y) contains supplementary material, which is available to authorized users.
“…Since lysosomal proteases are abundant in tumor cells but not healthy organs [30], Lin et al designed protease-mediated drug release systems [31]. The cytotoxic drug methotrexate (MTX) was attached to PEG and chitosan-coated SPIO via a protease-cleavable amide linker.…”
Superparamagnetic nanoparticles of iron oxides (SPIO) have been intensively studied for the development of contrast agents in magnetic resonance imaging (MRI). First generation SPIO had diagnostic capabilities only, while a new generation of SPIO have multifunctional characteristics for combined therapeutic and diagnostic applications. These theranostic nanoparticles hold great potential for image-guided cancer therapies. Especially, polymer-coated theranostic SPIO have enjoyed increasing attention due to good biocompatibility, biodegradability and versatile functionality endowed by polymeric matrices. This review provides an overview of recently developed polymer-coated multifunctional SPIO for cancer theranostics and discusses current challenges and future perspectives.
“…Functionalized nanoparticles (NPs) with various linkers and functional groups have been developed as carriers for drugs, 1-3 genes. 4,5 They can be further decorated with targeting agents such as antibodies (Abs) 6-8 and aptamers (Aps) 9,10 used for targeted imaging and therapy – an approach the so-called diapeutics/theranostics.…”
Introduction: Growing advances in nanotechnology have facilitated the applications of newly emerged nanomaterials in the field of biomedical/pharmaceutical sciences. Following this trend, the multifunctional nanoparticles (NPs) play a significant role in development of advanced drug delivery systems (DDSs) such as diapeutics/theranostics used for simultaneous diagnosis and therapy. Multifunctional radiolabeled NPs with capability of detecting, visualizing and destroying diseased cells with least side effects have been considered as an emerging filed in presentation of the best choice in solving the therapeutic problems. Functionalized magnetic and gold NPs (MNPs and GNPs, respectively) have produced the potential of nanoparticles as sensitive multifunctional probes for molecular imaging, photothermal therapy and drug delivery and targeting.
Methods: In this study, we review the most recent works on the improvement of various techniques for development of radiolabeled magnetic and gold nanoprobes, and discuss the methods for targeted imaging and therapies.
Results: The receptor-specific radiopharmaceuticals have been developed to localized radiotherapy in disease sites. Application of advanced multimodal imaging methods and related modality imaging agents labeled with various radioisotopes (e.g., 125I, 111In, 64Cu, 68Ga, 99mTc) and MNPs/GNPs have significant effects on treatment and prognosis of cancer therapy. In addition, the surface modification with biocompatible polymer such as polyethylene glycol (PEG) have resulted in development of stealth NPs that can evade the opsonization and immune clearance. These long-circulating agents can be decorated with homing agents as well as radioisotopes for targeted imaging and therapy purposes.
Conclusion: The modified MNPs or GNPs have wide applications in concurrent diagnosis and therapy of various malignancies. Once armed with radioisotopes, these nanosystems (NSs) can be exploited for combined multimodality imaging with photothermal/photodynamic therapy while delivering the loaded drugs or genes to the targeted cells/tissues. These NSs will be a game changer in combating various cancers.
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