Potential Theranostic Platform Research Articles

Multifunctional PVCL nanogels enable magnetic resonance imaging and immunostimulated radiotherapy of orthotopic glioblastoma

Despite radiotherapy (RT) is considered as an indispensable treatment that improves clinical symptoms and survival rates of glioblastoma multiforme (GBM), the overall survival time of GBM based on multimodal treatment synergic with RT is still unsatisfying. Herein, we designed an immunostimulated nanoplatform consisting of MnO2 and cytosine-phosphorothioate-guanine oligodeoxynucleotides (CpG ODNs) within the poly(N-vinylcaprolactam) nanogels (PVCL-MnO2-CpG NGs) for magnetic resonance imaging (MRI)-guided immuno-activated RT against GBM. In this system, I) CpG ODNs can be protected by PVCL NGs from degradation, which can increase the cellular uptake by immune cells and promote the activation of Toll-like receptor 9 (TLR9) pathway, thus enhance the immune responses to assist the therapeutic efficacy of tumour RT. II) PVCL-MnO2-CpG NGs are able to be dissociated to release Mn2+ in the tumour microenvironment, resulting in excellent T1-weighted tumour MRI along with the activation of cyclic GMP–AMP synthase/stimulator of interferon genes (cGAS/STING) pathway and elevated secretion of type-I interferons (IFN-I) in the downstream. III) MnO2 can also act as nanoenzyme to relieve tumour radioresistance through increasing the reactive oxygen species (ROS) level. Compared with RT alone, combinational immunoradiotherapy remarkably promotes the proportion of cytotoxic T cells (CD3+CD8+) and exhibits systemic therapeutic efficacy. Thus, MnO2 and CpG ODNs-loaded PVCL NGs may serve as a potential theranostic platform for MRI-guided immunostimulated RT of GBM.

Phase-Transitional Bismuth-Based Metals enable Rapid Embolotherapy, Hyperthermia, and Biomedical Imaging.

Embolization has been an important minimally invasive therapy for occlusion of malfunctioned vasculature and tumor treatment via target delivering embolic agents. The limitation of conventional embolic agents, such as fabrication process, precipitation time, invisibility, and lack of integrated functions often leads to insufficient embolization efficacy. To overcome these drawbacks, a multifunctional bismuth (Bi)-based liquid embolic agent for simultaneous realization of embolotherapy, thermotherapy, as well as high-contrast biomedical imaging is proposed. Benefitting from the suitable melting point, flexible nature, metallic merit, and easygoing operation via injection, the versatile embolic agent can achieve rapid liquid-solid phase transition, magnetic hyperthermia, and multimodal imaging capability. The Bi-based materials are demonstrated with excellent arteriovenous embolization efficiency and favorable biocompatibility according to in vivo investigations. Introduction of the liquid embolic agent to tumor arteries achieves evident tumor regression and rather clear imaging under computed tomography (CT), magnetic resonance imaging(MRI), and thermographs for consistently tracking the implants over the biological body. Further, the combined therapy coupled with thermotherapy exhibits improved therapeutic efficiency with formation of necrosis and total tumor eradiation at day 15after the treatment. The present innovative embolic agent and the surgical principle provide a promising modality for embolization and potential theranostic platform of tumors.

Theranostic Platforms Based on Silica and Magnetic Nanoparticles Containing Quinacrine, Chitosan, Fluorophores, and Quantum Dots.

In this paper, we describe the synthesis of multilayer nanoparticles as a platform for the diagnosis and treatment of ischemic injuries. The platform is based on magnetite (MNP) and silica (SNP) nanoparticles, while quinacrine is used as an anti-ischemic agent. The synthesis includes the surface modification of nanoparticles with (3-glycidyloxypropyl)trimethoxysilane (GPMS), the immobilization of quinacrine, and the formation of a chitosan coating, which is used to fix the fluorophore indocyanine green (ICG) and colloidal quantum dots AgInS2/ZnS (CQDs), which serve as secondary radiation sources. The potential theranostic platform was studied in laboratory animals.

A Second Near-Infrared Ru(II) Polypyridyl Complex for Synergistic Chemo-Photothermal Therapy.

The clinical success of cisplatin ushered in a new era of the application of metallodrugs. When it comes to practice, however, drug resistance, tumor recurrence, and drug systemic toxicity make it implausible to completely heal the patients. Herein, we successfully transform an electron acceptor [1, 2, 5]thiadiazolo[3,4-g]quinoxaline into a novel second near-infrared (NIR-II) fluorophore H7. After PEGylation and chelation, HL-PEG2k exhibits a wavelength bathochromic shift, enhanced photothermal conversion efficiency (41.77%), and an antineoplastic effect against glioma. Its potential for in vivo tumor tracking and image-guided chemo-photothermal therapy is explored. High levels of uptake and high-resolution NIR-II imaging results are thereafter obtained. The hyperthermia effect could disrupt the lysosomal membranes, which in turn aggravate the mitochondria dysfunction, arrest the cell cycle in the G2 phase, and finally lead to cancer cell apoptosis. HL-PEG2k displays a superior biocompatibility and thus can be a potential theranostic platform to combat the growth and recurrence of tumors.

Assembling Defined DNA Nanostructure with Nitrogen-Enriched Carbon Dots for Theranostic Cancer Applications.

DNA nanostructures as scaffolds for drug delivery, biosensing, and bioimaging are hindered by its vulnerability in physiological settings, less favorable of incorporating arbitrary guest molecules and other desirable functionalities. Noncanonical self-assembly of DNA nanostructures with small molecules in an alternative system is an attractive strategy to expand their applications in multidisciplinary fields and is rarely explored. This work reports a nitrogen-enriched carbon dots (NCDs)-mediated DNA nanostructure self-assembly strategy. Given the excellent photoluminescence and photodynamic properties of NCDs, the obtained DNA/NCDs nanocomplex holds great potential for bioimaging and anticancer therapy. NCDs can mediate DNA nanoprism (NPNCD ) self-assembly isothermally at a large temperature and pH range in a magnesium-free manner. To explore the suitability of NPNCD in potential biomedical applications, the cytotoxicity and cellular uptake efficiency of NPNCD are evaluated. NPNCD with KRAS siRNA (NPNCD K) is further conjugated for KRAS-mutated nonsmall cell lung cancer therapy. The NPNCD K shows excellent gene knockdown efficiency and anticancer effect in vitro. The current study suggests that conjugating NCDs with programmable DNA nanostructures is a powerful strategy to endow DNA nanostructures with new functionalities, and NPNCD may be a potential theranostic platform with further fine-tuned properties of CDs such as near-red fluorescence or photothermal activities.

Fluorescent tumor-targeted polymer-bioconjugate: A potent theranostic platform for cancer therapy

Polymer bioconjugate theranostics with inherent fluorescence and tumor targeting properties offers the advantage of diagnosis via fluorescence imaging and tumor targeted cancer therapy in a single platform without any requirement of external probes. Herein, fluorescent tumor targeted polymer biomolecule conjugate (comprising of cancer cell specific biotin moieties) was synthesized as potential theranostic platform for cancer therapy. The polymer biomolecule conjugate (PFBT-B) was used as a non-toxic, tumor-targeted, and fluorescent (greenish-yellow fluorescence) coating on magnetite nanoparticles (MNPs, a probable hyperthermia agent) and subsequently loaded with chemotherapeutic drug 5-Fluorouracil (5FU). The MNPs showed a saturation magnetization of 56.28 emu/g and coercivity of 75.5 Oe. The coating of MNPs with PFBT-B was confirmed from TEM studies which showed an average shell thickness of 1.88 nm. Drug (5FU) loading studies revealed a loading capacity of ~6.64 μg/μg of PFBT-B, while release studies showed pH-sensitive release profiles with accelerated release of drug in acidic milieu. MTT assay showed enhanced cytotoxicity of 5FU in the nanoformulated form as compared to pure 5FU. Additionally, PFBT-B coated MNPs showed preferential localization into the HeLa cancer cells as compared to HEK 293T normal cells. The inherent fluorescence and tumor targeting properties, thus, indicate that PFBT-B could serve as potential theranostic platform for cancer therapy.

Rhomboidal Pt(II) metallacycle-based NIR-II theranostic nanoprobe for tumor diagnosis and image-guided therapy.

Fluorescent theranostics probes at the second near-IR region (NIR-II; 1.0-1.7 µm) are in high demand for precise theranostics that minimize autofluorescence, reduce photon scattering, and improve the penetration depth. Herein, we designed and synthesized an NIR-II theranostic nanoprobe 1 that incorporates a Pt(II) metallacycle 2 and an organic molecular dye 3 into DSPE-mPEG5000 (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000]). This design endows 1 with good photostability and passive targeting ability. Our studies show that 1 accurately diagnoses cancer with high resolution and selectively delivers the Pt(II) metallacycle to tumor regions via an enhanced permeability and retention effect. In vivo studies reveal that 1 efficiently inhibits the growth of tumor with minimal side effects. At the same time, improved fluorescent imaging quality and signal-to-noise ratios are shown due to the long emission wavelengths. These studies demonstrate that 1 is a potential theranostic platform for tumor diagnosis and treatment in the NIR-II region.

Multifunctional Nanohybrid Based on Porous Silicon Nanoparticles, Gold Nanoparticles, and Acetalated Dextran for Liver Regeneration and Acute Liver Failure Theranostics

Herein, a novel nanohybridbased on porous silicon, gold nanoparticles (Au NPs), and acetalated dextran (DPSi/DAu@AcDEX) is reported to encapsulate and deliver one drug and increase the computer tomography (CT) signal for acute-liver-failure (ALF) theranostics. A microfluidic-assisted method is used to co-encapsulate different NPs in a single step. By alternating the surface properties of different NPs and by modulating the composition of the organic phase, both PSi and Au NPs are effectively encapsulated into the polymer matrix simultaneously, thus further achieving a multifunctional application. This system can be used to identify pathologically changes in the tissues and selectively deliver drugs to these sites. The loading of a therapeutic compound (XMU-MP-1) improves the drug solubility, precise, in situ drug delivery, and the drug-functioning time. In vivo results confirm a superior treatment effect and better compliance of this newly developed nanoformulation than free compound. This nanosystem plays a crucial role in targeting the lesion area, thus increasing the local drug concentration important for ALF reverse-effect. Moreover, the residence of Au NPs within the matrix further endows our system for CT-imaging. Altogether, these results support that this nanohybrid is a potential theranostic platform for ALF.

Multifunctional near-infrared dye-magnetic nanoparticles for bioimaging and cancer therapy

Theranostics based on nanoparticles have developed rapidly in the past decade and have been widely used in the diagnosis and treatment of liver cancer, breast cancer, and other tumors. However, for skin cancers, there are limited studies. In the present study, we successfully synthesized a theranostic nanoparticle by grating IR820 onto the surface of chitosan-coated magnetic iron oxide, IR820-CS-Fe3O4, showing an excellent magnetic resonance imaging (MRI) capability and cytotoxic effects against melanoma under irradiation with a near-infrared (NIR) laser (808 nm) in vitro. Furthermore, good stability for up to 8 days and negligible cytotoxicity were observed. These characteristics are important for biomedical applications of nanoparticles. In conclusion, we provide a novel and potential theranostic platform for melanoma treatment and detection.

One-pot synthesis of FePt/CNTs nanocomposites for efficient cellular imaging and cancer therapy

Here, we developed a facile route to synthesize carbon nanotube-based FePt nanocomposites (FePt/CNTs) as a potential theranostic platform in the cancer treatment. FePt/CNTs were firstly synthesized via one-pot polyol route, and then functionalized with 6-arm-polyethylene glycol-amine polymer. The average size of FePt nanoparticles (NPs) is 3–4 nm, which is dispersed on the CNT surface (ca.50–150 nm). The as-prepared FePt NPs display high cytotoxicity by highly reactive oxygen species in cancer cells. Folic acid and fluorescein isothiocyanate are assembled onto the surface of FePt/CNTs for effective targeting of folate receptor-positive cancer cells and simultaneously for the visualization of cellular uptake. Therefore, the FePt/CNTs NPs capability of simultaneously performing diagnosis, therapy, and targeting is, therefore, promising for future potential widespread application in biomedicine.

Design of multifunctional FePt/GO nanocomposites for targeting, dual-modal imaging diagnostic and in situ therapeutic potential theranostic platform

In this work, highly monodispersed chemically disordered face centered cubic (fcc) FePt nanoparticles (NPs) were assembled on graphene oxide (GO) surface to form FePt/GO nanocomposites via a simple polyol protocol.

Mesoporous Europo‐Gadolinosilicate Nanoparticles as Bimodal Medical Imaging Agents and a Potential Theranostic Platform

The mesoporous structure of sol-gel prepared gadolinium and europium doped silicate nanoparticles has been found to be highly dependent on the formulated composition, with synthesised samples displaying both disordered and hexagonally ordered mesoporous packing symmetry. The degree of pore ordering within the nanoparticles has a strong correlation with the total lanthanide (Gd(3+) and Eu(3+) ) concentration. The gadolinosilicates are excellent magnetic resonance imaging (MRI) longitudinal (T1 ) agents. The longitudinal relaxivity (r1 ) and transverse (r2 ) relaxivity, a measure of MRI contrast agent efficiency, were up to four times higher than the clinically employed Omniscan (gadodiamide); with r1 up to 20.6 s(-1) mM(-1) and r2 of 66.2 s(-1) mM(-1) compared to 5.53 and 4.64 s(-1) mM(-1) , respectively, for Omniscan. In addition, the europium content of all the samples studied is below the self-quenching limit, which results in a strong luminescence response from the nanoparticles on excitation at 250 nm. The Eu-Gd silicate nanoparticles act as bimodal imaging agents for MRI and luminescence. These mesoporous nanoparticles also have the potential to serve as encapsulation and controlled release matrices for pharmaceuticals. They are therefore a promising multimodal theranostic platform.

Controlled Molecular Targeting of Inducible Heat Shock Proteins

In an effort to devise schemes to site-specifically deliver drugs “on demand” we have leveraged the inducible expression properties of the well-characterized class of stress-response factors, the heat shock proteins. We asked whether a small molecule ligand selective for such proteins could be used as a potential theranostic platform. By conjugating a fluorescent dye to a recently identified nucleoside analog with modest affinity for heat shock protein 70 (HSP70), we have found that cellular uptake can be enhanced following transient heat shock in vitro. The in vivo performance of this compound was further evaluated in nude mice subjected to locoregional hyperthermia which showed a modest level of accumulation in the treated muscle. This effect correlates with relative levels of HSP70 over expression in the treated tissue, supporting the hypothesis that molecular targeting can be enhanced by inducing endogenous proteins through external means.