In vivo Imaging-Guided Nanoplatform for Tumor Targeting Delivery and Combined Chemo-, Gene- and Photothermal Therapy.

Currently, a large number of anti-tumor drug delivery systems have been widely used in cancer therapy. However, due to the molecular complexity and multidrug resistance of tumors, monotherapies remain suboptimal. Thus, this study aimed to develop a multifunctional theranostic nanoplatform for effective cancer therapy. Methods: Folic acid-modified silver sulfide@mesoporous silica core-shell nanoparticle was first modified with desthiobiotin (db) on the surface, then doxorubicin (DOX) was loaded into pore. Avidin was employed as "gatekeeper" to prevent leakage of DOX via desthiobiotin-avidin interaction. Db-modified survivin antisense oligonucleotide (db-DNA) which could inhibit survivin expression was then grafted on avidin at the outer layer of nanoparticle. DOX release and db-DNA dissociation were simultaneously triggered by overexpressing biotin in cancer cells, then combining PTT from Ag2S QD to inhibit tumor growth. Results: This nanoprobe had satisfactory stability and photothermal conversion efficiency up to 33.86% which was suitable for PTT. Due to the good targeting ability and fluorescent anti-bleaching, its signal still existed at the tumor site after tail vein injection of probe into HeLa tumor-bearing nude mice for 48 h. In vitro and in vivo antitumor experiments both demonstrated that drug, gene and photothermal synergistic therapy significantly enhanced antitumor efficacy with minimal systemic toxicity. Conclusion: Our findings demonstrate that this novel nanoplatform for targeted image-guided treatment of tumor and tactfully integrated chemotherapy, photothermal therapy (PTT) and gene therapy might provide an insight for cancer theranostics.

Graphene oxide coating core-shell silver sulfide@mesoporous silica for active targeted dual-mode imaging and chemo-photothermal synergistic therapy against tumors.

The accurate treatment of tumors with the help of multimodality imaging is of great significance. Herein, a novel multifunctional probe combining active targeted fluorescent imaging (FL)/photoacoustic imaging (PA) and chemo-photothermal therapy for tumors has been designed. Targeting molecule folate (FA) modified graphene oxide (GO) was used to coat core-shell silver sulfide@mesoporous silica (QD@Si) while antitumoral doxorubicin (DOX) was loaded in mesoporous channels by electrostatic adhesion, and a delivery system (QD@Si-D/GO-FA) for active targeted dual-mode imaging and synergistic chemo-photothermal for tumors was successfully obtained. Experiments showed the cell survival rate was 76.3 ± 4.6% when the probe concentration reached 0.5 mg mL-1, and demonstrated that the probe had good biocompatibility. In vivo and in vitro results indicated that this probe could be used for active targeted FL/PA for tumors with overexpressed FA receptors. The temperature of the tumor rose to 63.5 °C under laser irradiation, and the tumor could be killed more effectively after combination with chemotherapy, which was caused by exfoliation of GO from QD@Si-D/GO-FA after irradiation. These results showed that the probe had great potential for application in oncology and is expected to provide evidence for early diagnosis and treatment of tumors.

Nitrogen-doped graphene quantum dot for direct fluorescence detection of Al3+ in aqueous media and living cells.

Graphene quantum dot (GQD) has been attractive in analytical science field due to its low toxicity, stable photoluminescence. Herein, nitrogen-doped GQD (N-GQD) was prepared by a facile solvothermal treatment of GO using dimethylformamide, and exhibited a green emission with 23.1% quantum yield. The N-GQD probe showed a selective and sensitive fluorescence enhancement response to Al3+, the mechanism might be the formation of a complex between Al3+ and N-GQD constrained the photo-induced electron transfer (PET) process of N-GQD itself. With Benesi-Hildebrand equation, the binding constant and molar ratio between N-GQD and Al3+ was calculated to be 4.6 × 104Lmol-1 and 1:1 respectively. The pKa value of N-GQD was also determined to be 4.4 by capillary electrophoresis. In pH 4.0 PBS solution, there was a good linear relation between the fluorescence intensity and the logarithm of concentration of Al3+ in the range of 2.5-75µmolL-1, the limit of detection (3σ) was 1.3µmolL-1. This "Off - On" fluorescence method had been applied to accurate quantification of aluminum in hydrotalcite tablets. What's more, the fluorescence switch property of N-GQD was explored by alternate addition of Al3+ and EDTA. The probe was also utilized for detection Al3+ in living cells due to its excellent biocompatibility.

In Vivo Computed Tomography/Photoacoustic Imaging and NIR-Triggered Chemo-Photothermal Combined Therapy Based on a Gold Nanostar-, Mesoporous Silica-, and Thermosensitive Liposome-Composited Nanoprobe.

Safe multifunctional nanoplatforms that have multiple therapeutic functions integrated with imaging capabilities are highly desired for biomedical applications. In this paper, targeted chemo-photothermal synergistic therapy and photoacoustic/computed tomography imaging of tumors were achieved by one novel multifunctional nanoprobe (GMS/DOX@SLB-FA); it was composed of a gold nanostar core and a doxorubicin (DOX)-loaded mesoporous silica shell (GMS), which was coated with a folic acid (FA)-modified thermosensitively supported lipid bilayer (SLB-FA) as a gatekeeper. The multifunctional probe had perfect dispersion and stability; 2.1 nm mesoporous pores and 208 nm hydration particle sizes were obtained. In vitro studies indicated that the drug-loaded probe had excellent ability to control the release of DOX, with 71.98 ± 2.52% cumulative release after laser irradiation, which was significantly higher than that of unirradiated control group. A survival rate of 72.75 ± 4.37% of HeLa cells at 57.75 µg/mL probe also demonstrated the low cytotoxicity of the targeted probe. Both in vitro and in vivo results showed that the probe could achieve targeted photoacoustic imaging of tumors because of the fact that the FA-modified probe could specifically recognize the overexpressed FA receptors on tumor cells; meanwhile, the probe could also achieve the chemo-photothermal synergistic therapy of tumors through controlling the drug release from mesoporous channels by a near-infrared laser. Therefore, the probe had great potential in the early diagnosis and treatment of cancer.