Construction and application of a liver cancer-targeting drug delivery system based on core–shell gold nanocages

Abstract

BackgroundIn order to achieve drug targeting and controlled release, we have successfully developed a novel drug release system DOX/AuNCs-PM-HA with gold nanocages (AuNCs) as photothermal cores, thermally responsive copolymer P(NIPAM-co-Am) (PM) as the near-infrared (NIR) stimuli gatekeeper and hyaluronic acid as a targeting ligand as well as a capping agent.MethodsCell uptake and cell viability were investigated. In vivo photoacoustic tomography imaging in H22 tumor bearing mice was analyzed for the tumor targeting effect of the nanocomplexes. Antitumor efficacy and the tissue distribution in vivo were investigated.ResultsIn vitro results demonstrated that the DOX/AuNCs-PM-HA had significant anticancer activity against SMMC-7721 cells under NIR irradiation. Furthermore, in vivo photoacoustic tomography imaging of the nanocomplexes in H22 tumor bearing mice could indicate effective tumor targeting. Our studies on antitumor efficacy and the tissue distribution in vivo showed that many DOX/AuNCs-PM-HA nanocomplexes could efficiently accumulate at the tumor site so that they could inhibit the tumor growth effectively with limited side effects. The in vitro and in vivo results confirmed that the tumor-targeting and controlled-release drug system DOX/AuNCs-PM-HA with the combination of chemotherapy and photothermal therapy showed strong anti-tumor effect and would have great potential for future cancer therapy.ConclusionThis tumor targeting DOX/AuNCs-PM-HA nanocomplex responded not only to the external stimuli of NIR, but also the internal stimuli of hyaluronidase, providing the potential for pinpointed and multi-stimuli responsive intracellular drug release.

Molecularly Imprinting Polymers (MIP) Based on Nitrogen Doped Carbon Dots and MIL-101(Fe) for Doxorubicin Hydrochloride Delivery

“…To evaluate the potential application of the constructed MIP nanoparticles in DDS, the cytotoxicity tests of MIP and N-MIL on HepG2 cells and HL-7702 cells [ 41 , 42 , 43 , 44 , 45 , 46 ] were detected by MTT method ( Figure 8 ). The cell viability showed that the inhibition rate increased with time increasing.…”

Inorganic nanomaterials for chemo/photothermal therapy: a promising horizon on effective cancer treatment

“…Using high-molecular weight HA alongside with PEG can improve the biocompatibility and limit the release of encapsulated drugs in undesired sites (Wang et al 2014b;Sun et al 2017). In order to stimulate the drug release in the target tissue during the photothermal treatment, thermosensitive polymers are excellent coating materials (Deng et al 2016;Ji et al 2018). As Ji et al reported, almost complete controlled drug release was achieved by coating the GNCs with thermally responsive P (NIPAMco-Am) copolymer as a NIR stimuli gatekeeper (Ji et al 2018).…”

“…In order to stimulate the drug release in the target tissue during the photothermal treatment, thermosensitive polymers are excellent coating materials (Deng et al 2016;Ji et al 2018). As Ji et al reported, almost complete controlled drug release was achieved by coating the GNCs with thermally responsive P (NIPAMco-Am) copolymer as a NIR stimuli gatekeeper (Ji et al 2018). Although coating the nanoparticle with a variety of polymers provides controlled drug delivery, the early removal of nanoparticles by the immune system needs to be addressed.…”

“…Gold-based nanoparticles are among the first generations of nanomaterials introduced for combination therapy due to their deep-seated application as PTT agent (Huang et al 2006). By altering the size or shape of nanoparticles, their surface plasmon resonance can be adjusted to the wavelength in the NIR region to achieve the maximum thermal conversion for PTT application (Kim et al 2017;Li Volsi et al 2017;Ji et al 2018). In an optimized condition, a temperature of above 42 is achievable in a short time with a low laser power density.…”

Modelling the human heart: human stem cell-based models lead the way in physiological, pathological, and toxicological research

“…(60) As a consequence of this metabolic switch, mitochondrial respiration in the neonatal heart accounts for ~90% of the total ATP production, with a 10-fold increase in fatty acid oxidation, making it the dominant resource for oxidative phosphorylation. (60)(61)(62)(63) To accommodate this increased rate of β-oxidation, the mitochondria in neonatal CMs rapidly proliferate, relocate from perinuclear to peri-myofibrillar locations in the cell, and become more mature, leading to increased inner membrane surface area (the lamellar phenotype) and a 2-4 fold increase in expression of proteins involved in respiratory activity. The metabolic switch from a fetal to an adult phenotype coincides with a higher concentration of gene expression of key regulators in fatty acid transport and oxidation (60), such as peroxisome proliferator-activated receptor (PPAR)-α and γ. PPARs can exhibit their function only after establishing a transcriptional complex with their co-activators, such as PPARγ coactivator-1α (PGC-1α).…”