In this work, we developed a new pH- and temperature-responsive nanochemotherapeutic system based on Doxorubicin (DOX) noncovalently bound to biosynthesized gelatin-coated gold nanoparticles (DOX-AuNPs@gelatin). The real-time release profile of DOX was evaluated at different pH values (7.4, 5.3, and 4.6) and temperatures (22-45 °C) in aqueous solutions, and its therapeutic performance was examined in vitro against MCF-7 breast cancer cells. TEM, dark-field scattering, and wide-field fluorescence microscopy indicated the effective uptake of nanochemotherapeutics with the subsequent release and progressive accumulation of DOX in cell nuclei. MTT assays clearly showed the effectiveness of the treatment by inhibiting the growth of MCF-7 breast cancer cells for a loaded drug concentration of 5 μg/mL. The most informative data about the dynamic release and localization were provided by scanning confocal microscopy using time-resolved fluorescence and surface-enhanced Raman scattering (SERS) techniques. In particular, fluorescence-lifetime imaging (FLIM) recorded under 485 nm pulsed diode laser excitation revealed the bimodal distribution of DOX in cells. The shorter fluorescence lifetime of DOX localized in nuclei (1.52 ns) than in the cytoplasm (2.4 ns) is consistent with the cytotoxic mechanism induced by DOX-DNA intercalation. Remarkably, the few DOX molecules captured between nanoparticles ("electromagnetic hotspots") after most drug is released act as SERS reporters for the localization of plasmonic nanocarriers in MCF-7 cells. The high drug loading capacity and effective drug release under pH control combined with the advantage of multimodal visualization inside cells clearly indicate the high potential of our DOX-AuNPs@gelatin delivery system for implementation in nanomedicine.

The bioactive glasses can lead to the promotion of growth of granulation tissue, while the gold nanoparticles (AuNPs) can induce the acceleration of wound healing including tissue regeneration, connective tissue formation, and angiogenesis. The aim of this study was to evaluate the impact of using the bioactive glass (BG) and BG-AuNPs composites on skin wound healing in experimental rat models for 14 days. Sol–gel derived BGs and BG-AuNPs composites mixed with Vaseline at 6, 12 and 18 wt% were used to evaluate the repair response of the skin. During the process of healing, granulomatous reaction was observed in the wound treated with 12 and 18 wt% BG-Vaseline ointments. Furthermore, a strong vascular proliferation and complete wound regeneration were found in 18%BG-AuNPs-Vaseline treated groups. The results derived from the performed investigations revealed that the 18% BG-AuNPs-Vaseline ointment is a promising candidate for wound healing applications.

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There is still a lack of available techniques to follow noninvasively the intracellular processes as well to track or disentangle various signals from the therapeutic agents at the site of action in the target cells. We present here the assessment of the intracellular kinetics of doxorubicin (DOX) and gold nanoparticle (AuNP) carriers by mapping simultaneously fluorescence and photoluminescence signals by fluorescence lifetime imaging microscopy under two-photon excitation (TPE-FLIM). The new nano–chemotherapeutic system AuNPs@gelatin–hyd–DOX has been fabricated by DOX loading onto the surface of gelatin-biosynthesized AuNPs (AuNPs@gelatin) through a pH-sensitive hydrazone bond. The successful loading of DOX onto the AuNPs was studied by spectroscopic methods and steady-state fluorescence, and the nanosystem pH-responsive character was validated under simulated biological conditions at different pH values (i.e., pH 4.6, 5.3, and 7.4). Considering that the fluorescence lifetime of DOX molecules at a specific point in the cell is a reliable indicator of the discrimination of the different states of the drug in the internalization path, i.e., released versus loaded, the kinetics of AuNPs@gelatin–hyd–DOX cellular uptake and DOX release was compared to that of free DOX, resulting in two different drug internalization pathways. Finally, cell viability tests were conducted against NIH:OVCAR-3 cell line to prove the efficiency of our chemotherapeutic nanosystem. TPE-FLIM technique could be considered promising for noninvasive, high-resolution imaging of cells with improved capabilities over current one-photon-excited FLIM.

Ovarian cancer is a common cause of cancer death in women and is associated with the highest mortality rates of all gynecological malignancies. Carboplatin (CBP) is the most used cytotoxic agent in the treatment of ovarian cancer. Herein, we design and assess a CBP nanotherapeutic delivery system which allows combinatorial functionalities of chemotherapy, pH sensing, and multimodal traceable properties inside live NIH:OVCAR-3 ovarian cancer cells. In our design, a pH-sensitive Raman reporter, 4-mercaptobenzoic acid (4MBA) is anchored onto the surface of chitosan-coated silver nanotriangles (chit-AgNTs) to generate a robust surface-enhanced Raman scattering (SERS) traceable system. To endow this nanoplatform with chemotherapeutic abilities, CBP is then loaded to 4MBA-labeled chit-AgNTs (4MBA-chit-AgNTs) core under alkaline conditions. The uptake and tracking potential of CBP-4MBA-chit-AgNTs at different Z-depths inside live ovarian cancer cells is evaluated by dark-field and differential interference contrast (DIC) microscopy. The ability of CBP-4MBA-chit-AgNTs to operate as near-infrared (NIR)-responsive contrast agents is validated using two noninvasive techniques: two-photon (TP)-excited fluorescence lifetime imaging microscopy (FLIM) and confocal Raman microscopy (CRM). The most informative data about the precise localization of nanocarriers inside cells correlated with intracellular pH sensing is provided by multivariate analysis of Raman spectra collected by scanning CRM. The in vitro cell proliferation assay clearly shows the effectiveness of the prepared nanocarriers in inhibiting the growth of NIH:OVCAR-3 cancer cells. We anticipate that this class of nanocarriers holds great promise for application in image-guided ovarian cancer chemotherapy.

The hallmark of Alzheimer’s disease (AD) pathogenesis is believed to be the production and deposition of amyloid-beta (Aβ) peptide into extracellular plaques. Existing research indicates that extracellular vesicles (EVs) can...