Naphthalimide-based Functional Glycopolymeric Nanoparticles as Fluorescent Probes for Selective Imaging of Tumor Cells.

A series of functional glycopolymer nanoparticles with 1,8-naphthalimide motif was designed, synthesized and applied for tumor cell imaging. With the pH-sensitive and aggregation-induced emission (AIE) effect of the 1,8-naphthalimide fluorescent probe, the presence of glucose-based glycopolymers enhanced its water-solubility and biocompatibility. Owing to the dual tumor-targeting effects of the dense glucose part and the boronic ester modification, the obtained glycopolymers showed high affinity to tumor cells, with a much faster staining rate than normal cells, indicating a great potential for diagnosis and treatments of cancers.

Theranostic GO-based nanohybrid for tumor induced imaging and potential combinational tumor therapy.

Graphene oxide (GO)-based theranostic nanohybrid is designed for tumor induced imaging and potential combinational tumor therapy. The anti-tumor drug, Doxorubicin (DOX) is chemically conjugated to the poly(ethylenimine)-co-poly(ethylene glycol) (PEI-PEG) grafted GO via a MMP2-cleavable PLGLAG peptide linkage. The therapeutic efficacy of DOX is chemically locked and its intrinsic fluorescence is quenched by GO under normal physiological condition. Once stimulated by the MMP2 enzyme over-expressed in tumor tissues, the resulting peptide cleavage permits the unloading of DOX for tumor therapy and concurrent fluorescence recovery of DOX for in situ tumor cell imaging. Attractively, this PEI-bearing nanohybrid can mediate efficient DNA transfection and shows great potential for combinational drug/gene therapy. This tumor induced imaging and potential combinational therapy will open a window for tumor treatment by offering a unique theranostic approach through merging the diagnostic capability and pathology-responsive therapeutic function.

Supramolecular self-assembled peptide-engineered nanofibers: A propitious proposition for cancer therapy.

Cancer is a devastating disease that causes a substantial number of deaths worldwide. Current therapeutic interventions for cancer include chemotherapy, radiation therapy, or surgery. These conventional therapeutic approaches are associated with disadvantages such as multidrug resistance, destruction of healthy tissues, and tissue toxicity. Therefore, there is a paradigm shift in cancer management wherein nanomedicine-based novel therapeutic interventions are being explored to overcome the aforementioned disadvantages. Supramolecular self-assembled peptide nanofibers are emerging drug delivery vehicles that have gained much attention in cancer management owing to their biocompatibility, biodegradability, biomimetic property, stimuli-responsiveness, transformability, and inherent therapeutic property. Supramolecules form well-organized structures via non-covalent linkages, the intricate molecular arrangement helps to improve tissue permeation, pharmacokinetic profile and chemical stability of therapeutic agents while enabling targeted delivery and allowing efficient tumor imaging. In this review, we present fundamental aspects of peptide-based self-assembled nanofiber fabrication their applications in monotherapy/combinatorial chemo- and/or immuno-therapy to overcome multi-drug resistance. The role of self-assembled structures in targeted/stimuli-responsive (pH, enzyme and photo-responsive) drug delivery has been discussed along with the case studies. Further, recent advancements in peptide nanofibers in cancer diagnosis, imaging, gene therapy, and immune therapy along with regulatory obstacles towards clinical translation have been deliberated.

Fluorescent and theranostic probes for imaging nicotinamide phosphoribosyl transferase (NAMPT).

Nicotinamide phosphoribosyl transferase (NAMPT) has been regarded as an attractive target for cancer therapy. However, there is a lack of chemical tools for real-time visualization and detection of NAMPT. Herein, the first fluorescent and theranostic probes were designed for imaging NAMPT, which had dual functions of diagnosis and treatment. The designed probes possessed good affinity and environmental sensitivity to NAMPT with a turn-on mechanism and were successfully applied in fluorescence detecting and imaging of NAMPT at the level of living cells and tissue sections. They also effectively inhibited tumor cell proliferation and arrested cell cycle at the G2 phase. These fluorescent probes enabled detection and visualization of NAMPT, representing effective chemical tools for the pathological diagnosis and treatment of cancer.

A porous form Coomassie brilliant blue G250-isorhamnetin fluorescent composite coated with acrylic resin for tumor cell imaging.

Four distinct fluorescence complexes, the fluorescent complex-1 (FC-1), fluorescent complex-2 (FC-2), fluorescent complex third (FC-3) and fluorescent complex fourth (FC-4), were created using isorhamnetin and Coomassie brilliant blue G250 as raw materials. The issue of isorhamnetin's low solubility has been resolved, and isorhamnetin-coomassie brilliant blue G250 now has better biocompatibility. Four different forms of fluorescence compounds' ultraviolet absorption spectra were identified. It was discovered that FC-2, FC-3, and FC-4, respectively, had double peaks at 483-620 nm. FC-4 had the highest ultraviolet absorption intensity, whereas FC-1 exhibited the most consistent and longest wavelength of ultraviolet absorption. Transmission electron microscopy revealed that the acrylic resin evenly disseminated the Coomassie brilliant blue G250-isorhamnetin complex in an amorphous flocculent form. Human prostate cancer cells (PC3) and human cervical cancer cells (HeLa) were investigated in the (Cell Counting Kit-8) CCK8 experiment under 10 different concentration circumstances, and the proliferation impact was 64.30% and 68.06%, respectively. Shown the complex's strong anti-tumor properties and minimal cytotoxicity. Through in vitro imaging of tumor cells, it was found that FC-1's fluorescent complex has high selectivity and can accurately infiltrate tumor cells, proving that it is biocompatible. The design not only addresses the issue of isorhamnein-Coomassie Bright Blue G250's bioavailability, but it also has an effective visual fluorescence targeting effect.

Glyconanoparticles with Activatable Near-Infrared Probes for Tumor-Cell Imaging and Targeted Drug Delivery.

Background: Multifunctional nanocarriers based on tumor targeting and intracellular monitoring have received much attention and been a subject of intensive study by researchers in recent years. In this study, we report multifunctional glyconanoparticles with activatable near-infrared probes for tumor imaging and targeted drug delivery. Methods: Disulfide-functionalized dicyanomethylene-4H-pyran (DCM-SS-NH2) and amino-functionalized lactose were modified and loaded onto the surfaces of polydopamine nanoparticles (NPs) by Michael addition or Schiff-base reaction as GSH stimulation-responsive fluorescent probes and tumor-targeting moieties, respectively. Doxorubicin (DOX), a model anticancer drug, was loaded onto polydopamine through π-π interactions directly to prepare multifunctional PLDD (PDA@Lac/DCM/DOX) NPs. Results: Experimental results showed that PLDD NPs had been successfully prepared. DCM, the fluorescence of which was quenched in PLDD NPs, was able to restore red fluorescence in a solution with a GSH concentration of 5 mM. The amount of DOX released from PLDD NPs was 44% over 72 hours in a weak-acid environment (pH 5). The results of CLSM and flow cytometry indicated that the PLDD NPs had good HepG2-targeting ability due to the special recognition between lactose derivative of NPs and overexpressed asialoglycoprotein receptors on HepG2 cell membrane. More importantly, the disulfide bond of DCM-SS-NH2 was broken by the high concentration of GSH inside cancer cells, activating the near-infrared fluorescence probe DCM for cancer-cell imaging. MTT assays indicated that PLDD NPs exhibited higher anticancer efficiency for HepG2 cells and had reduced side effects on normal cells compared with free DOX. Conclusion: The fluorescence of modified DCM loaded onto PLDD NPs is able to be restored in the high-concentration GSH environment within cancer cells, while improving the effectiveness of chemotherapy with reduced side effects. It provides a good example of integration of tumor imaging and targeted drug delivery.

Tumor cell-on fluorescence imaging agent using hyaluronate dots.

We report here the use of near-infrared fluorescent dye-labelled hyaluronate (HA) dot named HDFc for tumor imaging. We took advantage of the unique auto-quenching characteristic that occurs when the fluorescent dye molecules are in close proximity to one another under ordinary conditions. However, when the HDFc is located in tumor cells, the tumor cell-specific enzyme (e.g., hyaluronidase: HAase) affects the structure of the HDFc, followed by the transition from auto-quenched dye molecules to dequenched dye molecules, resulting in the identification of the tumor cells. For this purpose, HDFcs were synthesized, characterized, and exogenously treated with HAase to demonstrate the enzyme-dependent HDFc photoactivity. Specifically, confocal microscopy and flow cytometry confirmed the efficient cellular internalization and fluorescence production of HDFc in CD44+ and HAase-abundant tumor cells. Collectively, this study opens the door for utilizing polymeric dots to visualize tumor cells by introducing biocompatible HA and tumor cell-on photoluminescent dye.

Folic acid-modified fluorescent dye-protein nanoparticles for the targeted tumor cell imaging.

Serum albumin has a wide range of applications in biochemical experiments and pharmaceutical field. We found that a cyanine dye, dimethylindole red (Dir), could selectively interact with bovine serum albumin (BSA). Dir exhibited very weak red fluorescence, while the fluorescence intensity at 630 nm was enhanced up to 130-fold upon noncovalently interacting with 30 µM BSA. Besides, Dir showed a highly selective response to BSA over human serum albumin (HSA). For the detection of BSA, a limit of detection as low as 23 nM was obtained. Then biocompatible Dir-BSA nanoparticles were prepared by the desolvation technique. The Dir-BSA nanoparticles possess excellent fluorescence properties with a quantum yield of 32%. Furthermore, folic acid as a targeting group was conjugated to Dir-BSA nanoparticles and these nanoparticles were characterized by TEM and laser particle analyzer, etc. Folic acid-modified Dir-BSA nanoparticles were successfully used for tumor cell-targeted imaging.

Chitosan-Stabilized Self-Assembled Fluorescent Gold Nanoclusters for Cell Imaging and Biodistribution in Vivo.

Biocompatible, near-infrared luminescent gold nanoclusters were synthesized in situ using as-prepared chitosan grafted with N-acetyl-l-cysteine (NAC-CS). The fluorescent gold nanoclusters coated with chitosan-N-acetyl-l-cysteine (AuNCs@NAC-CS) were aggregated by multiple ultrasmall gold nanoclusters closing with each other, with strong fluorescence emission at 680 nm upon excitation at 360 nm. AuNCs@NAC-CS did not display any appreciable cytotoxicity on cells even at a concentration of 1.0 mg mL-1. AuNCs@NAC-CS were more insensitive to H2O2 and trypsin compared with fluorescent gold nanoclusters coated with Albumin Bovine V (AuNCs@BSA), which make them have long time imaging in HeLa cells. Furthermore, the obvious fluorescence signal of AuNCs@NAC-CS appeared in the liver and kidney of the normal mice after 6 h injection. And the fluorescence intensity decreased after that because of the highly efficient clearance characteristics of ultrasmall nanoparticles. These findings demonstrated that AuNCs@NAC-CS possessed good fluorescence, low cytotoxicity, and low sensitivity to some content of cells, allowing imaging of the living cells.

Self-production of oxygen system CaO2 /MnO2 @PDA-MB for the photodynamic therapy research and switch-control tumor cell imaging.

Photodynamic therapy (PDT) holds promise in biochemical study and tumor treatment. A novel multifunctional nanosystem CaO2 /MnO2 @polydopamine (PDA)-methylene blue (MB) nanosheet (CMP-MB) was designed. CaO2 nanoparticles were encapsulated by MnO2 nanosheet, and then PDA was coated on the surface of CaO2 /MnO2 nanosheets, which could adsorb photosensitizer MB through hydrophobic interaction or π-π stacking. In this nanosystem, CaO2 /MnO2 had the ability of self-production of oxygen, which solved the problem of tumor hypoxia largely. Moreover, it is worth mentioning that the fluorescence of MB was suppressed by MnO2 , while its emission was triggered in the simulated tumor microenvironment. Therefore, CMP-MB nanosheet could be used to switch-control cell imaging potentially. 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide testing and Live/Dead assay confirmed CMP-MB nanosheet had fewer side effects without illumination while it destroyed Hela cell with the illumination of light. Vitro cell experiment demonstrated CMP-MB nanosheet could achieve tumor microenvironment responsive imaging and inhibit tumor cell growth under illumination effectively. Therefore, the system has great potential for PDT application and switch-control tumor cell imaging. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2544-2552, 2018.

Extremely High Two-Photon Absorbing Graphene Oxide for Imaging of Tumor Cells in the Second Biological Window.

Cancer, a life-threatening disease, has become a global pandemic. Targeted tumor imaging using near-infrared (NIR) light is the key to improve the penetration depth and it is highly promising for clinical tumor diagnostics. Driven by this need, in this Letter we have reported aptamer conjugated graphene oxide-based two-photon imaging of breast tumor cells selectively. Reported data indicate that there is an extremely high two-photon absorption from aptamer conjugated graphene oxide (σ2PA = 46890 GM). Experimental data show that two-photon luminescence signal remains almost unchanged even after 2 h of illuminations. Reported results show that S6 RNA aptamers conjugated graphene oxide-based two-photon fluorescence can be used for selective two-photon imaging of SK-BR-3 breast tumor cell in second biological transparency windows using 1100 nm wavelength. Experimental data demonstrate that it is highly capable of distinguishing targeted breast cancer SK-BR-3 cells from other nontargeted MDA-MB-231 breast cancer cells.