Hybridized quantum dot, silica, and gold nanoparticles for targeted chemo-radiotherapy in colorectal cancer theranostics.

Multimodal nanoparticles, utilizing quantum dots (QDs), mesoporous silica nanoparticles (MSNs), and gold nanoparticles (Au NPs), offer substantial potential as a smart and targeted drug delivery system for simultaneous cancer therapy and imaging. This method entails coating magnetic GZCIS/ZnS QDs with mesoporous silica, loading epirubicin into the pores, capping with Au NPs, PEGylation, and conjugating with epithelial cell adhesion molecule (EpCAM) aptamers to actively target colorectal cancer (CRC) cells. This study showcases the hybrid QD@MSN-EPI-Au-PEG-Apt nanocarriers (size ~65 nm) with comprehensive characterizations post-synthesis. In vitro studies demonstrate the selective cytotoxicity of these targeted nanocarriers towards HT-29 cells compared to CHO cells, leading to a significant reduction in HT-29 cell survival when combined with irradiation. Targeted delivery of nanocarriers in vivo is validated by enhanced anti-tumor effects with reduced side effects following chemo-radiotherapy, along with imaging in a CRC mouse model. This approach holds promise for improved CRC theranostics.

Synthesis of a targeted, dual pH and redox-responsive nanoscale coordination polymer theranostic against metastatic breast cancer in vitro and in vivo.

BACKGROUND: Nanoscale coordination polymers (nCP) have exhibited a great potential in designing of the theranostic platforms in the latest years. However, they have low selectivity for cancerous tissues and require to be modified for becoming effective cancer therapeutics. In this study, a novel nanoscale pH and redox-responsive coordination polymer with high selectivity was synthesized. METHODS: The nCP was synthesized by iron(III) chloride and dithiodiglycolic acid. After loading the prepared nCP with doxorubicin (DOX), nCP was coated with an amphiphilic copolymer composed of α-tocopheryl succinate-polyethylene glycol (VEP). Next, AS1411 aptamer was decorated on the VEP shell of the DOX-loaded nCP (Apt-VEP-nCP@DOX) to provide a guided drug delivery platform. RESULTS: The prepared platform demonstrated high DOX loading capacity and pH and redox-responsive DOX release. Apt-VEP-nCP@DOX displayed greater DOX internalization and toxicity toward breast cancer cells of 4T1 and MCF7 compared with that of non-targeted VEP-nCP@DOX. Also, the intravenous injection of Apt-VEP-nCP@DOX (a single dose) considerably suppressed the 4T1 tumor growth in vivo. Moreover, Apt-VEP-nCP@DOX showed outstanding magnetic resonance (MR) imaging capability for 4T1 adenocarcinoma diagnosis in ectopic 4T1 tumor model in mice. CONCLUSIONS: The developed innovative intelligent Apt-VEP-nCP@DOX could serve as a safe and biocompatible theranostic platform appropriate for further translational purposes against breast cancer.

Improving anti-cancer drug delivery performance of magnetic mesoporous silica nanocarriers for more efficient colorectal cancer therapy.

BACKGROUND: Improving anti-cancer drug delivery performance can be achieved through designing smart and targeted drug delivery systems (DDSs). For this aim, it is important to evaluate overexpressed biomarkers in the tumor microenvironment (TME) for optimizing DDSs. MATERIALS AND METHODS: Herein, we designed a novel DDS based on magnetic mesoporous silica core-shell nanoparticles (SPION@MSNs) in which release of doxorubicin (DOX) at the physiologic pH was blocked with gold gatekeepers. In this platform, we conjugated heterofunctional polyethylene glycol (PEG) onto the outer surface of nanocarriers to increase their biocompatibility. At the final stage, an epithelial cell adhesion molecule (EpCAM) aptamer as an active targeting moiety was covalently attached (Apt-PEG-Au@NPs-DOX) for selective drug delivery to colorectal cancer (CRC) cells. The physicochemical properties of non-targeted and targeted nanocarriers were fully characterized. The anti-cancer activity, cellular internalization, and then the cell death mechanism of prepared nanocarriers were determined and compared in vitro. Finally, tumor inhibitory effects, biodistribution and possible side effects of the nanocarriers were evaluated in immunocompromised C57BL/6 mice bearing human HT-29 tumors. RESULTS: Nanocarriers were successfully synthesized with a mean final size diameter of 58.22 ± 8.54 nm. Higher cytotoxicity and cellular uptake of targeted nanocarriers were shown in the EpCAM-positive HT-29 cells as compared to the EpCAM-negative CHO cells, indicating the efficacy of aptamer as a targeting agent. In vivo results in a humanized mouse model showed that targeted nanocarriers could effectively increase DOX accumulation in the tumor site, inhibit tumor growth, and reduce the adverse side effects. CONCLUSION: These results suggest that corporation of a magnetic core, gold gatekeeper, PEG and aptamer can strongly improve drug delivery performance and provide a theranostic DDS for efficient CRC therapy.

Five new complexes with deferiprone and N,N-donor ligands: evaluation of cytotoxicity against breast cancer MCF-7 cell line and HSA-binding determination.

In this study, five new complexes containing deferiprone (dfp) and N,N-donor ligands [bipyridine (bpy), 1,10-phenanthroline (phen) and ethylenediamine (en)] were synthesized: [Fe(dfp)2(bpy)](PF6) (1), [Fe(dfp)2(phen)](PF6) (2), [Cu2(dfp)2(bpy)2](PF6)2 (3), [Ga(dfp)2(bpy)](PF6) (4), and [Fe(dfp)2(en)](PF6) (5). Characterization of these complexes was carried out through elemental analysis and FT-IR, and single-crystal X-ray crystallography was used to determine their structures. Whilst the polyhedron has a distorted octahedral geometry in 1, 2, 4, and 5, it adopts a distorted square-pyramidal geometry in 3. Interaction of these compounds with human serum albumin (HSA) has been investigated through electronic absorption and fluorescence titration techniques. Emission quenching was performed separately for each complex at three different temperatures and thermodynamic parameters were calculated using binding constants to better understand the power of different binding forces with the HSA. Results demonstrated that compounds interact strongly with the HSA with a static quenching mechanism. Our evaluation of the cytotoxicity of complexes against the breast cancer MCF-7 cell line showed that complex 2 presents a better cytotoxicity than the standard cis-Pt. Finally, using the AutoDock 4.2 program, simulations to analyze the mechanism of complex-HSA interactions and their binding mode were carried out. Results showed that the best binding mode is located in subdomain IB for 1, 2, and 4, in I/II for 3, and in IA/IIA for 5. Communicated by Ramaswamy H. Sarma.

Targeted rod-shaped mesoporous silica nanoparticles for the co-delivery of camptothecin and survivin shRNA in to colon adenocarcinoma in vitro and in vivo.

Simultaneous drug and gene delivery to cancer cells has been introduced to provide advantages of the synergistic effects of gene to sensitize the cancer cells to chemotherapeutic agent. In the current study, nucleolin-targeted co-delivery system, based on PEGylated rod-shaped mesoporous silica NPs was developed as a biocompatible nanocarrier for simultaneous delivery of camptothecin and survivin shRNA-expressing plasmid (iSur-DNA) to colon adenocarcinoma. The structural characterization including hydrodynamic radius and morphological characteristics of the prepared system demonstrated the mesoporous rod-shaped structure of the prepared system with 100-150 nm diameter. Camptothecin was loaded into the rod-shaped MSN NPs with encapsulation efficiency of 32%. At the next stage, the prepared camptothecin-loaded system was PEGylated and then iSur-DNA was condensed with C/P ratio of 6 to form PEG@MSNR-CPT/Sur. Then, the prepared camptothecin-iSur-DNA loaded PEGylated rod-shaped mesoporous silica NPs were tagged with AS1411 DNA aptamer (Apt-PEG@MSNR-CPT/Sur) in order to provide selective therapy against colorectal adenocarcinoma. The obtained results showed that the prepared platform controlled the release of anticancer drug, camptothecin. The experimental results indicated potent synergistic effect of iSur-pDNA and CPT in in vitro cytotoxicity, apoptosis induction and in vivo antitumor effect. In addition, tagging the system with AS1411 DNA aptamer facilitated drug uptake into nucleolin positive colorectal cancer cells leading to higher cellular toxicity and apoptosis induction in C26 cells compared to nucleolin-negative CHO cell line. Apt-PEG@MSNR-CPT/Sur system significantly supressed tumor growth rate in C26 tumor bearing mice while improving survival rate and pharmacokinetics of the platform in comparison with PEG@MSNR-CPT and PEG@MSNR-CPT/Sur. It could be concluded that the developed nucelolin targeted nanomedicine for co-delivery of camptothecin and iSur-DNA could serve as a versatile nanotherapeutic system against colorectal cancer.