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The objective of this study is to utilize the pH sensitivity of modified mesoporous silica nanoparticles (MSN) for oral drug delivery. In the first time, a pH-sensitive ionic liquid was synthesized through the quaternization of 3-aminopropyltrimethoxysilane (3-ATMS) with sodium monochloroacetate (SMCA). Then, silica nanoparticle was modified by this pH-sensitive ionic liquid and converted to a pH-sensitive positive-charge silica nanoparticle (PCSN). The nanoparticle was characterized by FTIR and SEM. Naproxen as anionic drug molecules was entrapped in this pH-sensitive positive-charge silica nanoparticles (PCSN) and the in vitro release profiles were established separately in both (SGF, pH 1) and (SIF, pH 7.4).

Background Combination chemo-photothermal therapy appears to be one of the next generations of cancer treatment. In this study hollow gold nanostars (HGNSs) and gold nanocages (GNCs) were synthesized and stabilized with thermo-pH-sensitive thiol-end capped ABC triblock copolymer poly(acrylic acid)-b-poly(N isopropylacrylamide)-b-poly (e-caprolactone)-SH; PAA-b-PNIPAAm-b-PCL-SH (GNSs@Pol). Doxorubicin (Dox) was conjugated to the GNSs@Pol nanostructures via ionic interaction, covalent attachment and hydrogen bonding (GNSs@Dox-Pol). The physicochemical characteristics of prepared GNSs@Pol and GNSs were assessed using dynamic light scattering (DLS), transmission electron microscopy (TEM) and zeta potential techniques. Cytocompatibility of the GNSs@Pol was studied by hemolysis assay and MTT assay. The chemo-photothermal therapy (PTT) potential of GNSs@Dox-Pol was compared on MCF7 cells using MTT assay, cell cycle, DAPI staining and Annexin-V apoptosis assay techniques. Results Cell internalization results showed an almost complete uptake of GNSs@Pol by MCF-7 cells in the first 3 h of treatment. The heat generation measurement results showed that both of GNSs have a potential for light to heat conversion (∆T = 23–27 ºC) and HGNSs demonstrated better efficiency than GNCs after 10-min exposure to NIR irradiation. Following chemo-photothermal treatment, the highest cell mortality (90%) and apoptotic effects (97% apoptosis) were observed in HGNSs@Dox-Pol received laser irradiation treatment group. Conclusions This work highlights the potential application of designed GNSs@Dox-Pol in a combinational chemo-PTT to treat breast cancer cells. Graphic abstract

To improve the efficacy of cancer therapeutics, highly sensitive imaging with precise accuracy is mandatory for timely diagnosis and selection of strategic approaches. Despite recent advances in technologies associated with tumor imaging, the application of conventional single-mode imaging is the subject of debate. Herein, two types of pH-responsive gold-polymer nanostructures, GNSts and GNRs, containing CD and MTX, GNSts-MTX@CD-Pol and GNRs-MTX@CD-Pol were designed. Dual-imaging modalities (fluorescence and CT imaging) and synergistic chemo-photothermal therapy were examined in human breast cancer MDA-MB 231 cells. MTT assay showed NIR irradiation of cells pre-treated with synthesized nanoparticles promoted tumoricidal synergy via the reduction of survival rate after 48 hours in comparison with the control group (p<0.05), indicating a high absorption coefficient in the NIR area and efficient heat production rate. Flow cytometry, real-time PCR and western blot, analyses indicated an apoptotic cell death induced by the up-regulation of Caspases 3, 6, 7, 8, and 9, Bax, and Annexin-V, confirming the activation of intrinsic and extrinsic apoptosis pathways inside the host cells. The elevation of p27 and p53 in line with the increase of cell percent at the subG1 phase showed apoptotic changes and inhibition of dynamic cell growth compared to the non-treated cells (p<0.05). Evident fluorescence intensity at lower pH values (6.3) showed pH-dependent activity of nanoparticles internalized by surface folate receptor. Of note, we showed strong capability for CT imaging in cells incubated with GNSts-MTX@CD-Pol and GNRs-MTX@CD-Pol. Taken together, all data show that gold-polymer nanostructures have considerable capability in theranostic applications like simultaneous diagnostic imaging and therapy.