Theranostic nanoparticles with multifunctional ability have been emerging as a new platform for biomedical applications such as imaging, sensing and drug delivery. Despite gold nanorods (Au NRs) being an excellent nanosource with multifunctional versatility, they have certain limitations in biomedical applications, which include surfactant toxicity, biological stability and controlled drug release kinetics. Herein, we have developed Au NR-doxorubicin conjugates (DOX@PSS-Au NR) with improved drug loading efficiency (55 AE 6%) and minimum CTAB toxicity, by employing Au NRs (4.4 AE 0.5 aspect ratio) coated with poly(sodium 4-styrenesulfonate) (PSS). DOX@PSS-Au NR conjugates exhibited higher biological stability with sustained drug release kinetics at pH 5. The binding events of DOX molecules onto the PSS coated gold nanorods (PSS-Au NRs) were monitored through fluorescence quenching and the longitudinal surface plasmon resonance signals. Furthermore the anti-cancer potential and apoptosis inducing efficiency of DOX@PSS-Au NR conjugates in MCF-7 cells revealed higher therapeutic efficiency than free DOX, as corroborated through morphological assessment and in vitro cytotoxicity assay. In addition, DOX@PSS-Au NR conjugates showed efficient cellular entry and uniform intracellular distribution, suggesting the augmenting effect of chemotherapeutic drugs by Au NRs. Thus DOX@PSS-Au NR conjugates demonstrate significant therapeutic potential, suggesting their potential in anticancer therapy.
Plasmonic nanoparticles have been widely used in photomedicine owing to their unique photophysical properties including surface plasmon resonance, high optical extinction and extensive thermal stability, which makes metal nanoparticles more suitable for application in cancer phototherapy. Here, we exploit the appropriateness of chitosan reduced gold nanoparticles (AuNPs) as a photothermal converter, photodynamic carrier and contrast agent in the applications of bioimaging, photothermal (PTT) and photodynamic therapy (PDT), concurrently to destroy the human breast cancer cells (MCF-7). AuNPs were successfully conjugated by non-covalent interaction with hydrophilic photosensitizer, acridine orange (AO) through glutathione (GSH) to achieve improved PDT and PTT therapy. This could be attributed to the high loading efficiency with enhanced cellular uptake and excellent photothermal stability of the nanoconjugate (AO@GSH-AuNPs). In addition, the anticancer activity of the nanoconjugate in combination with blue light irradiation (l ¼ 492 nm) demonstrated a pronounced effect compared to the free AO or light irradiation. Thus results of our studies represent the dual mode action of both AO and AuNPs showing photodynamic and photothermal ablation, respectively. Our findings suggest that the AO@GSH-AuNPs nanoconjugate could be used as a multifunctional probe for anticancer therapy.
Gold Nanospheres (AuNS) have been widely explored as an emerging system for various biomedical applications including drug delivery, bioimaging and photomedicine. However, method of synthesizing nanoparticles and its toxicity including bioaccumulation has been a problem of concern. In the present study, we explored the appropriateness of 12.0 ±1.99 nm chitosan reduced AuNS in vivo models with respect to its bioavailability and toxicity against various concentrations (2.5-7.5 mg/kg). Administration of AuNS did not show any signs of morbidity. Inductively coupled plasma optical emission spectrometry (ICP-OES) analysis of blood (0.156 ± 0.154), urine (0.084 ± 0.08) and tissues indicates gradual dissipation and obligatory clearance within 24 h time interval. Nevertheless, pres- ence of AuNS in blood after 24 h confirms the bioavailability of AuNS demonstrating the evidence for no immune clearance and efficient tissue uptake. Further, brain shows the lowest quantity of injected AuNS. From this result, we determine this chitosan monolayer protected AuNS could cross the blood brain barrier and enter to the neural tissues. Interestingly there was no evidence of toxicity in any of the organs. In conclusion, our data suggest that AuNS injected though tail vain were easily taken up by tissues and does not produce sub-acute physiological damage even at high concentrations tested, supporting chitosan reduced AuNS as biocompatible, nontoxic nanoconjugates for targeted drug delivery and other biomedical applications.
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