Delivery of vincristine sulfate-conjugated gold nanoparticles using liposomes: a light-responsive nanocarrier with enhanced antitumor efficiency

Abstract

Rapid drug release at the specific site of action is still a challenge for antitumor therapy. Development of stimuli-responsive hybrid nanocarriers provides a promising strategy to enhance therapeutic effects by combining the unique features of each component. The present study explored the use of drug–gold nanoparticle conjugates incorporated into liposomes to enhance antitumor efficiency. A model drug, vincristine sulfate, was physically conjugated with gold nanoparticles and verified by UV-visible and fourier transform infrared spectroscopy, and differential scanning calorimetry. The conjugates were incorporated into liposomes by film dispersion to yield nanoparticles (113.4 nm) with light-responsive release properties, as shown by in vitro release studies. Intracellular uptake and distribution was studied in HeLa cells using transmission electron microscopy and confocal laser scanning microscopy. This demonstrated liposome internalization and localization in endosomal–lysosomal vesicles. Fluorescence intensity increased in cells exposed to UV light, indicating that this stimulated intracellular drug release; this finding was confirmed by quantitative analyses using flow cytometry. Antitumor efficacy was evaluated in HeLa cells, both in culture and in implants in vivo in nude mice. HeLa cell viability assays showed that light exposure enhanced liposome cytotoxicity and induction of apoptosis. Furthermore, treatment with the prepared liposomes coupled with UV light exposure produced greater antitumor effects in nude mice and reduced side effects, as compared with free vincristine sulfate.

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“…1d, the absorption peak for GNPs (530 nm), intercross-linked GNPs (560 nm) and luminol-antibody bearing cross-linked GNPs (570 nm) have been compared. As seen after cross linking of GNPs the absorption peak was flattened and shifted to right owing to increase in particle size 18 . By immobilization of antibody and luminol on GNPs, the UV-Vis absorption peak was even shifted in some extend.…”

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“…Furthermore, NPs can transport hydrophilic or lipophilic molecular cargos [22]. The most attractive characteristics of NPs include their high surface-to-volume ratio that enables the loading of large amounts of drug into tumor tissues [149], their ability to increase the longevity of the treatment in circulation, controlled release upon physiological changes such as pH [150], and their ability to accumulate in solid tumor tissue by the enhanced permeability retention (EPR) effect [151]. In GBMs, EPR occurs by virtue of the highly angiogenic nature of GBMs which leads to the imperfect formation of new vascular vessels, and partial BBB disruption [152].…”

“…PEG and PEI are also functionalized through amine, carboxylic acids or maleimide groups to peptides, antibodies or any other ligands for active targeting [71,157,158]. Several liposomal formulations for cancer therapy have been approved by the Food and Drug Administration (FDA) [159,160], and have shown promising results in preclinical and clinical studies for drug delivery [150,161,162]. One example is a clinical trial phase I study for the delivery of a siRNA-containing liposomal formulation against EphA2 (Ephrin type-A receptor 2) to solid tumors (NCT01591356) [163].…”

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“…14,27,28 Due to successful results in preclinical and clinical studies, liposomes are currently the only nanoparticles approved by the FDA as drug delivery carriers. 16,17,[29][30][31] More recently, gold nanoparticles (AuNPs) have also gained acceptance as suitable drug delivery vehicles. 29,[32][33][34] AuNPs are biologically inert, easily synthesized, commercially available, and highly stable composites.…”

“…16,17,[29][30][31] More recently, gold nanoparticles (AuNPs) have also gained acceptance as suitable drug delivery vehicles. 29,[32][33][34] AuNPs are biologically inert, easily synthesized, commercially available, and highly stable composites. 35,36 They possess feasible characteristics that enable their application in diagnostics, imaging, and therapy.…”