Doxorubicin-Loaded Carbon Dots Lipid-Coated Calcium Phosphate Nanoparticles for Visual Targeted Delivery and Therapy of Tumor.

BACKGROUND: Carbon dots (CDs) have attracted extensive attention in recent years because of their high biocompatibility and unique optical property. But they could not be well applied in the drug delivery system to enable distribution in tumor sites with their low pH sensitivity. They are barriers for drug delivery. CDs as an imaging proper were conjugated with doxorubicin (DOX) lipid-coated calcium phosphate (LCP) nanoparticle, for a pH-sensitive nanocarrier and delivery of the antitumor drugs. MATERIALS AND METHODS: CDs were prepared by one-step hydrothermal treatment of citric acid and ethylenediamine. The nanoparticles were simply prepared by using microemulsion technology to form calcium phosphate (CaP) core and further coated with cationic lipids. RESULTS: The structure was characterized by FTIR, XRD and TEM. In vitro release study revealed that DOX-CDs@LCP was pH dependent. The cytotoxicity assay demonstrated that it exhibited enhanced efficiency compared to the control group (DOX-CDs), but weaker than free DOX. The cellular uptake revealed that these pH-sensitive nanoparticles could be taken up effectively and deliver DOX into the cytoplasm to reach antitumor effect. The fluorescence imaging indicated that DOX-CDs@LCP mostly distributed in the tumor region due to the enhanced permeability and retention effect (EPR) to reduce its systematical toxicity. Importantly, an antitumor activity study demonstrated that the DOX-CDs@LCP nanoparticles had higher antitumor activity than any other groups and lower toxicity. The results showed that LCP could significantly promote the release in tumor microenvironment due to pH-response. The DOX-CDs could enhance load capacity and reduce drug premature releasing; real-time tracking of efficacy as confocal imaging contrast agent. Thus, DOX-CDs@LCP had antitumor capacity and lower systematic toxicity in tumor therapy. CONCLUSION: DOX-CDs@LCP were proven as a promising tumor pH-sensitive and imaging-guided drug delivery system for liver cancer chemotherapy.

Multistage delivery of CDs-DOX/ICG-loaded liposome for highly penetration and effective chemo-photothermal combination therapy.

Nanoparticles (NPs) have proven to be effective drug carriers in diagnosis and therapy of cancer. But, they faced a contradictory issue that NPs with large size appear weak tumor penetration, meanwhile small size resulted in poor tumor retention. Herein, we fabricated doxorubicin conjugated carbon dots (CDs-DOX) and indocyanine green (ICG)-loaded liposomes (ICG-LPs) named CDs-ICG-LPs using a modified reverse phase evaporation process, and with high incorporation in the aqueous core. The CDs-ICG-LPs exhibited good monodispersity, excellent fluorescence/size stability, and consistent spectra characteristics compared with free ICG or DOX. Moreover, the CDs-ICG-LPs showed higher temperature response, faster DOX release under laser irradiation. In the meantime, the fluorescence of DOX and ICG in CDs-ICG-LPs was also visualized for the process of subcellular location in vitro. In comparison with chemo or photothermal treatment alone, the combined treatment of CDs-ICG-LPs with laser irradiation synergistically induced the apoptosis and death of DOX-sensitive HepG2 cells. In vivo antitumor activities demonstrated CDs-ICG-LPs could reach higher antitumor activity compared with CDs-DOX and ICG-LPs for H22 tumor cells, and suppressed H22 tumor growth in vivo. Notably, no systemic toxicity occurrence was observed after repeated dose of CDs-ICG-LPs with laser irradiation. Hence, the well-defined CDs-ICG-LPs exhibited great potential in targeting cancer imaging and chemo-photothermal therapy.

In vitro and in vivo evaluation of folate-mediated PEGylated nanostructured lipid carriers for the efficient delivery of furanodiene.

Furanodiene (FN) loaded FA-PEG2000-DSPE modified nanostructured lipid carriers (FA-FN-NLCs) were developed to increase the solubility and bioavailability of FN, prolong the circulation time in blood and improve the targeting ability. FA-FN-NLCs were prepared using emulsification-ultrasonic and low temperature-solidification method and optimized by central composition design (CCD). In vitro and in vivo characteristics of FA-FN-NLCs were investigated in detail. The optimized formulations exhibited a spherical shape with particle size of 127.4 ± 2.62 nm, PDI of 0.268 ± 0.04, zeta potential of -14.7 ± 1.08 mV, high encapsulation efficiency of 89.04 ± 2.26% and loading capacity of 8.46 ± 0.20%. Differential scanning calorimetry (DSC) indicated that FN was not in crystalline state in FA-FN-NLCs. In vitro drug release exhibited a biphasic release pattern which showed a relative burst drug release at the initial time and followed by a prolonged drug release. In vivo, compared with FN solution (FN-SOL) and FN loaded traditional NLCs (FN-NLCs), FA-FN-NLCs had a longer blood circulating time (t1/2) and higher area under the curve (AUC). NiR fluorescence imaging study demonstrated that FA-FN-NLCs specially accumulated in tumor site by the receptor-mediated endocytosis. This study showed that FA-FN-NLCs was a promising drug delivery system for FN in the treatment of cancer.

Doxorubicin conjugated functionalizable carbon dots for nucleus targeted delivery and enhanced therapeutic efficacy.

Carbon dots (CDs) have shown great potential in imaging and drug/gene delivery applications. In this work, CDs functionalized with a nuclear localization signal peptide (NLS-CDs) were employed to transport doxorubicin (DOX) into cancer cells for enhanced antitumor activity. DOX was coupled to NLS-CDs (DOX-CDs) through an acid-labile hydrazone bond, which was cleavable in the weakly acidic intracellular compartments. The cytotoxicity of DOX-CD complexes was evaluated by the MTT assay and the cellular uptake was monitored using flow cytometry and confocal laser scanning microscopy. Cell imaging confirmed that DOX-CDs were mainly located in the nucleus. Furthermore, the complexes could efficiently induce apoptosis in human lung adenocarcinoma A549 cells. The in vivo therapeutic efficacy of DOX-CDs was investigated in an A549 xenograft nude mice model and the complexes exhibited an enhanced ability to inhibit tumor growth compared with free DOX. Thus, the DOX-CD conjugates may be exploited as promising drug delivery vehicles in cancer therapy.