Spindle‐Like Polypyrrole Hollow Nanocapsules as Multifunctional Platforms for Highly Effective Chemo–Photothermal Combination Therapy of Cancer Cells in Vivo

The monodispersed spindle‐like polypyrrole hollow nanocapsules (PPy HNCs) as the multifunctional platforms for combining chemotherapy with photothermal therapy for cancer cells are reported. Whereas the hollow cavity of nanocapsules can be used to load the anticancer drug (i.e., doxorubicin) for chemotherapy, the PPy shells can convert NIR light into heat for photothermal therapy. The release of the drug from the spindle‐like PPy HNCs is pH‐sensitive and near‐infrared (NIR) light‐enhanced. More importantly, the spindle‐like PPy HNCs can penetrate cells more rapidly and efficiently in comparison with the spherical PPy HNCs. Both in vitro and in vivo experiments demonstrated that the combination of DOX‐loaded spindle‐like PPy HNCs and NIR light provide a highly effective and feasible chemo‐photothermal therapy cancer method with a synergistic effect. Owing to their high photothermal conversion efficiency, large hollow cavity, and good biocompatibility, the spindle‐like PPy HNCs could be used as a promising new cancer drug‐nanocarrier and photothermal agent for localized tumorous chemo‐photothermal therapy.     

Platinum(II)–Gadolinium(III) Complexes as Potential Single‐Molecular Theranostic Agents for Cancer Treatment

Theranostic agents are emerging multifunctional molecules capable of simultaneous therapy and diagnosis of diseases. We found that platinum(II)–gadolinium(III) complexes with the formula [{Pt(NH₃)₂Cl}₂GdL](NO₃)₂ possess such properties. The Gd center is stable in solution and the cytoplasm, whereas the Pt centers undergo ligand substitution in cancer cells. The Pt units interact with DNA and significantly promote the cellular uptake of Gd complexes. The cytotoxicity of the Pt–Gd complexes is comparable to that of cisplatin at high concentrations (≥0.1 mM ), and their proton relaxivity is higher than that of the commercial magnetic resonance imaging (MRI) contrast agent Gd–DTPA. T₁‐weighted MRI on B6 mice demonstrated that these complexes can reveal the accumulation of platinum drugs in vivo. Their cytotoxicity and imaging capabilities make the Pt–Gd complexes promising theranostic agents for cancer treatment.     

Hybrid Coordination Networks Constructed from ɛ‐Keggin‐Type Polyoxometalates and Rigid Imidazole‐Based Bridging Ligands as New Carriers for Noble‐Metal Catalysts

Three hybrid coordination networks that were constructed from ?‐Keggin polyoxometalate building units and imidazole‐based bridging ligands were prepared under hydrothermal conditions, that is, H[(Hbimb)₂(bimb){Zn₄PMo^V8Mo^VI₄O₄₀}] ? 6 H₂O ( 1 ), [Zn(Hbimbp)(bimbp)₃{Zn₄PMo^V8Mo^VI₄O₄₀}] ? DMF ? 3.5 H₂O ( 2 ), and H[Zn₂(timb)₂(bimba)₂Cl₂{Zn₄PMo^V8Mo^VI₄O₄₀}] ? 7 H₂O ( 3 ) (bimb=1,4‐bis(1‐imidazolyl)benzene, bimbp=4,4′‐bis(imidazolyl)biphenyl, timb=1,3,5‐tris(1‐imidazolyl)benzene, bimba=3,5‐bis(1‐imidazolyl)benzenamine). All three compounds were characterized by elemental analysis, IR spectroscopy, thermogravimetric analysis, and single‐crystal X‐ray diffraction. The mixed valence of the Mo centers was analyzed by XPS spectroscopy and bond‐valence sum calculations. In all three compounds, the ?‐Keggin polyoxometalate (POM) units acted as nodes that were connected by rigid imidazole‐based bridging ligands to form hybrid coordination networks. In compound 1 , 1D zigzag chains extended to form a 3D supramolecular architecture through intermolecular hydrogen‐bonding interactions. Compound 2 consisted of 2D curved sheets, whilst compound 3 contained chiral 2D networks. Because of the intrinsic reducing properties of ?‐Keggin POM species, noble‐metal nanoparticles were loaded onto these POM‐based coordination networks. Thus, compounds 1 – 3 were successfully loaded with Ag nanoparticles, and the corresponding composite materials exhibited high catalytic activities for the reduction of 4‐nitrophenol.     

Exploring the Potential of Metallodrugs as Chemotherapeutics for Triple Negative Breast Cancer

This review focuses on studies of coordination and organometallic compounds as potential chemotherapeutics against triple negative breast cancer (TNBC) which has one of the poorest prognoses and worst survival rates from all breast cancer types. At present, chemotherapy is still the standard of care for TNBC since only one type of targeted therapy has been recently developed. References for metal-based compounds studied in TNBC cell lines will be listed, and those of metal-specific reviews, but a detailed overview will also be provided on compounds studied in vivo (mostly in mice models) and those compounds for which some preliminary mechanistic data was obtained (in TNBC cell lines and tumors) and/or for which bioactive ligands have been used. The main goal of this review is to highlight the most promising metal-based compounds with potential as chemotherapeutic agents in TNBC.     

Direct Cytosolic Delivery of siRNA Using Nanoparticle‐Stabilized Nanocapsules

The use of nanoparticle‐stabilized nanocapsules (NPSCs) for the direct cytosolic delivery of siRNA is reported. In this approach, siRNA is complexed with cationic arginine‐functionalized gold nanoparticles by electrostatic interactions, with the resulting ensemble self‐assembled onto the surface of fatty acid nanodroplets to form a NPSC/siRNA nanocomplex. The complex rapidly delivers siRNA into the cytosol through membrane fusion, a mechanism supported by cellular uptake studies. Using destabilized green fluorescent protein (deGFP) as a target, 90 % knockdown was observed in HEK293 cells. Moreover, the delivery of siRNA targeting polo‐like kinase 1 (siPLK1) efficiently silenced PLK1 expression in cancer cells with concomitant cytotoxicity.     

Half‐Sandwich Ruthenium(II) Biotin Conjugates as Biological Vectors to Cancer Cells

Ruthenium(II)–arene complexes with biotin‐containing ligands were prepared so that a novel drug delivery system based on tumor‐specific vitamin‐receptor mediated endocytosis could be developed. The complexes were characterized by spectroscopic methods and their in vitro anticancer activity in cancer cell lines with various levels of major biotin receptor (COLO205, HCT116 and SW620 cells) was tested in comparison with the ligands. In all cases, coordination of ruthenium resulted in significantly enhanced cytotoxicity. The affinity of Ru^II–biotin complexes to avidin was investigated and was lower than that of unmodified biotin. Hill coefficients in the range 2.012–2.851 suggest strong positive cooperation between the complexes and avidin. To estimate the likelihood of binding to the biotin receptor/transporter, docking studies with avidin and streptavidin were conducted. These explain, to some extent, the in vitro anticancer activity results and support the conclusion that these novel half‐sandwich ruthenium(II)–biotin conjugates may act as biological vectors to cancer cells, although no clear relationship between the cellular Ru content, the cytotoxicity, and the presence of the biotin moiety was observed.     

Design and Synthesis of 2‐(5‐Phenylindol‐3‐yl)benzimidazole Derivatives with Antiproliferative Effects towards Triple‐Negative Breast Cancer Cells by Activation of ROS‐Mediated Mitochondria Dysfunction

Benzimidazole derivatives are widely studied because of their broad‐spectrum biological activity, such as antitumor properties and excellent fluorescence performance. Herein, two types of 2‐(5‐phenylindol‐3‐yl)benzimidazole derivatives ( 1 a – 1 h and 2 a – 2 e ) were rationally designed and synthesized. When these compounds were investigated in vitro anti‐screening assays, we found that all of them possessed antitumor effect, in particular compound 1 b , which showed an outstanding antiproliferative effect on MDA‐MB‐231 cells (IC₅₀≈2.6 μm ). A study of the drug action mechanisms in cells showed that the antitumor activity of the compounds is proportional to their lipophilicity and cellular uptake; the tested compounds all entered the lysosome of MDA‐MB‐231 cells and caused changes in the levels of reactive oxygen species (ROS), and then caused mitochondrial damage. Apparent differences in the ROS levels for each compound suggest that the lethality of these compounds towards MDA‐MB‐231 cells is closely related to the ROS levels. Taken together, this study not only provides a theoretical basis for 2‐(5‐phenylindol‐3‐yl)benzimidazole anticarcinogens but also offers new thinking on the rational design of next‐generation antitumor benzimidazole derivatives.     

Platinum (IV) Derivatives with Cinnamate Axial Ligands as Potent Agents Against Both Differentiated and Tumorigenic Cancer Stem Rhabdomyosarcoma Cells

To design an anticancer drug capable of inhibiting not only the proliferation of the differentiated tumor cells but also reducing the tumorigenic capability of cancer stem cells (CSCs), the new Pt^IV prodrugs with axial cinnamate ligands were synthesized. We demonstrate their superior antiproliferative activity in monolayer and 3D spheroid antiproliferative activity tests using panel of cancer cell lines. An outstanding activity was found against rhabdomyosarcoma cells, one of the most problematic and poorly treatable pediatric tumors. The results also suggest that the released Pt^II compound inhibits antiproliferative activity of cancer cells by DNA‐damage mediated mechanism; the released cinnamic acid can trigger processes leading to differentiation, making the CSCs more sensitive to killing by the platinum part of the complex. Pt^IV complex with axial cinnamate ligands is the first Pt^IV prodrug capable of overcoming CSCs resistance and induce death in both CSCs and bulk cancer.     

Targeted Tumor Computed Tomography Imaging Using Low‐Generation Dendrimer‐Stabilized Gold Nanoparticles

We report a facile approach to fabricating low‐generation poly(amidoamine) (PAMAM) dendrimer‐stabilized gold nanoparticles (Au DSNPs) functionalized with folic acid (FA) for in vitro and in vivo targeted computed tomography (CT) imaging of cancer cells. In this study, amine‐terminated generation 2 PAMAM dendrimers were employed as stabilizers to form Au DSNPs without additional reducing agents. The formed Au DSNPs with an Au core size of 5.5 nm were covalently modified with the targeting ligand FA, followed by acetylation of the remaining dendrimer terminal amines to endow the particles with targeting specificity and improved biocompatibility. Our characterization data show that the formed FA‐modified Au DSNPs are stable at different pH values (5—8) and temperatures (4–50 °C), as well as in different aqueous media. MTT assay data along with cell morphology observations reveal that the FA‐modified Au DSNPs are noncytotoxic in the particle concentration range of 0–3000 nM . X‐ray attenuation coefficient measurements show that the CT value of FA‐modified Au DSNPs is much higher than that of Omnipaque (a clinically used CT contrast agent) at the same concentration of the radiodense elements (Au or iodine). Importantly, the FA‐modified Au DSNPs are able to specifically target a model cancer cell line (KB cells, a human epithelial carcinoma cell line) over‐expressing FA receptors and they enable targeted CT imaging of the cancer cells in vitro and the xenografted tumor model in vivo after intravenous administration of the particles. With the simple synthesis approach, easy modification, good cytocompatibility, and high X‐ray attenuation coefficient, the FA‐modified low‐generation Au DSNPs could be used as promising contrast agents for targeted CT imaging of different tumors over‐expressing FA receptors.     

New Polyoxometalates Containing Hybrid Polymers and Their Potential for Nano‐Patterning

Two new polyoxometalate (POM)‐based hybrid monomers (Bu₄N)₅(H)[P₂V₃W₁₅O₅₉{(OCH₂)₃CNHCO(CH₃)C?CH₂}] ( 2 ) and (S(CH₃)₂C₆H₄OCOC(CH₃)=CH₂)₆[PVMo₁₀O₄₀] ( 5 ) were developed by grafting polymerizable organic units covalently or electrostatically onto Wells–Dawson and Keggin‐type clusters and were characterized by analytical and spectroscopic techniques including ESI‐MS and/or single‐crystal X‐ray diffraction analyses. Radical initiated polymerization of 2 and 5 with organic monomers (methacryloyloxy)phenyldimethylsulfonium triflate (MAPDST) and/or methylmethacrylate (MMA) yielded a new series of POM/polymer hybrids that were characterized by ¹H, ³¹P NMR and IR spectroscopic techniques, gel‐permeation chromatography as well as thermal analyses. Preliminary tests were conducted on these POM/polymer hybrids to evaluate their properties as photoresists using electron beam (E‐beam)/extreme ultraviolet (EUV) lithographic techniques. It was observed that the POM/polymer hybrid of 2 with MAPDST exhibited improved sensitivity under EUV lithographic conditions in comparison to the MAPDST homopolymer resist possibly due to the efficient photon harvesting by the POM clusters from the EUV source.     

Optically Active Liquid Crystalline Polyoxometalates via Electrostatic Encapsulation with Cholesterol‐Containing Amphiphile

A novel cholesterol‐containing amphiphile was designed and prepared in the study, which is a room‐temperature ionic liquid crystal over a broad temperature range with pronounced chiroptical properties. Four types of inorganic polyoxometalates (PMs) with different numbers of charges were encapsulated by the chiral amphiphile. The incorporation of chiral organic cations triggers achiral PMs in the complexes to show induced chirality through intermolecular interactions, as demonstrated by circular dichroism spectroscopy. The electrostatic encapsulation with mesomorphic promoters provides the inorganic PMs with liquid crystalline behavior, characterized by differential scanning calorimetry, polarized optical microscopy, and X‐ray diffraction. The strategy applied herein represents a unique example of liquid crystalline PM complexes with optical activity.     

Self-Assembly and Antitumor Activity of a Polyoxovanadate-Based Coordination Nanocage

A new supramolecular nanocage, VMOP- 31 , based on polyoxovanadate as the molecular building block, has been designed and synthesized under solvothermal conditions. The structure of VMOP- 31 was determined by single-crystal and powder X-ray diffraction, FTIR spectroscopy, UV/Vis spectrophotometry, and thermogravimetric analysis. The nanocage exhibits octahedral geometry and is constructed of six {V₅O₉Cl(COO)₄} at the vertices and eight TATB (H₃TATB=4,4′,4′′-(s-triazine-2,4,6-triyl)tribenzoic acid) ligands on the faces. Impressively, VMOP- 31 exhibited high efficiency in the inhibition of cell growth of solid tumors, such as human liver cancer cells SMMC-7721, and superior results in the treatment of liver tumors in mice compared with classic cisplatin. Detailed studies revealed that the potential mechanism of cell death induced by VMOP- 31 involves cell cycle arrests, DNA damage, and subsequent apoptosis. Moreover, VMOP- 31 exhibited negligible side effects in the mice compared with cisplatin. To the best of our knowledge, VMOP- 31 is the first supramolecular nanocage applied to hepatic tumors both in vitro and in vivo.     

A Cancer Therapeutic Vaccine based on Clustered Tn‐Antigen Mimetics Induces Strong Antibody‐Mediated Protective Immunity

Tumor‐associated carbohydrate antigens (TACAs) are key components of cancer vaccines. A variety of vaccines based on native TACAs such as α‐Tn have shown immunogenicity and protection in preclinical animal studies, however, their weak immunogenicity, low in vivo instability, and poor bioavailability, have discouraged their further evaluations in clinical studies. A new improved vaccine prototype is reported. It is composed of four clustered Tn‐antigen mimetics and a immunogenic peptide epitope that are conjugated to a cyclopeptide carrier. The immunization of mice with this vaccine 1) was safe, 2) induced a strong and long‐lasting Tn‐specific response with IgM/IgG antibodies able to recognize native carbohydrate antigens; 3) produced high titers of IgG1, IgG2a, and IgG3 antibodies; and 4) produced a significant antibody‐dependent regression of tumors and conferred protection. Altogether, these findings pave the way for the clinical development of safe and effective therapeutic vaccines against Tn‐expressing cancers.     

Engineering the Ionic Self‐Assembly of Polyoxometalates and Facial‐Like Peptides

The self‐assembly behavior of polyoxometalates (PMs) and facial‐like cationic peptides carrying lysine residues were systematically investigated. Circular dichroism and UV/Vis spectra demonstrated that the multivalent electrostatic attractions between polyanionic PMs and short peptides with protonated lysine residues initiated the conformational transition of peptide molecules from random‐coil to β‐sheet state, and subsequently the co‐assembly. TEM and atomic force microscopy (AFM) measurements showed that uniform nanofibers formed with decreasing size of the PMs or increasing the intermolecular forces of the peptides, such as through hydrogen‐bonding, hydrophobic, and/or π–π interactions. Additionally, the stability of the nanostructures can be improved by rational suppression of the electrostatic repulsion of the shell peptides covering the surface of the nanostructures. These results provide new insight into understanding the ionic self‐assembly of peptides and PMs and controlling their final morphology.     

Three Keggin‐Type Transition Metal‐Substituted Polyoxometalates as Pure Inorganic Photosensitizers for p‐Type Dye‐Sensitized Solar Cells

In light of the serious challenge of severe global energy shortages, p‐type dye‐sensitized solar cells (p‐DSSCs) have attracted increasing levels of interest. The potential of three Keggin‐type transition metal‐substituted polyoxometalates, TBA₈Na₂[SiW₉O₃₇{Co(H₂O)₃}]? 11 H₂O (SiW₉Co₃), TBA₄[(SiO₄)W₁₀Mn^III₂O₃₆H₆]?1.5 CH₃CN? 2 H₂O (SiW₁₀Mn^III₂), and TBA_3.5H_5.5[(SiO₄)W₁₀Mn^III/IV₂O₃₆]? 10 H₂O?0.5 CH₃CN (SiW₁₀Mn^III/IV₂) has been explored as pure inorganic dye photosensitizers for p‐DSSCs (TBA=(n‐C₄H₉)₄N⁺). The three dyes show overall conversion efficiencies of 0.038, 0.029, and 0.027 %, respectively, all of which are higher than that of coumarin 343 (0.017 %). These polyoxometalates are the first three pure inorganic dyes reported for use with p‐DSSCs and therefore demonstrate a new strategy for designing efficient dyes, especially pure inorganic dyes. Moreover, they broaden the range of applications for polyoxometalates.     

Near‐Infrared Light and pH‐Responsive Polypyrrole@Polyacrylic acid/Fluorescent Mesoporous Silica Nanoparticles for Imaging and Chemo‐Photothermal Cancer Therapy

We have rationally designed a new theranostic agent by coating near‐infrared (NIR) light‐absorbing polypyrrole (PPY) with poly(acrylic acid) (PAA), in which PAA acts as a nanoreactor and template, followed by growing small fluorescent silica nanoparticles (fSiO₂ NPs) inside the PAA networks, resulting in the formation of polypyrrole@polyacrylic acid/fluorescent mesoporous silica (PPY@PAA/fmSiO₂) core–shell NPs. Meanwhile, DOX‐loaded PPY@PAA/fmSiO₂ NPs as pH and NIR dual‐sensitive drug delivery vehicles were employed for fluorescence imaging and chemo‐photothermal synergetic therapy in vitro and in vivo. The results demonstrate that the PPY@PAA/fmSiO₂ NPs show high in vivo tumor uptake by the enhanced permeability and retention (EPR) effect after intravenous injection as revealed by in vivo fluorescence imaging, which is very helpful for visualizing the location of the tumor. Moreover, the obtained NPs inhibit tumor growth (95.6 % of tumors were eliminated) because of the combination of chemo‐photothermal therapy, which offers a synergistically improved therapeutic outcome compared with the use of either therapy alone. Therefore, the present study provides new insights into developing NIR and pH‐stimuli responsive PPY‐based multifunctional platform for cancer theranostics.