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In recent years, the material preparation technology has ushered into a stage of rapid development, increasingly more carbon materials are found to display superior properties, making them suitable for designing nano-scale devices. Within the applications of electronic devices, a considerable amount of consumed energy has to be converted into heat; thus the efficiency of heat transport inside these devices can largely determine their overall performance. Decent elucidations of the heat transport mechanisms within low-dimensional materials will be helpful to achieve thermal management control of the related devices and furthermore, to improve their conversion efficiency. It is well understood that the heat transport within these kinds of materials is largely associated with their structural features. In this study, we focused on a novel material, body centered cubic carbon (C14), which is composed of sp3 hybridized carbon atoms. Such a novel material displays superior electronic properties; however, its thermal properties remain to be investigated. In order to systematically evaluate the practical applicability of this novel material, first-principles calculations were employed to systematically solve its structure; furthermore, its thermal conductivity, phonon dispersion spectrum, phonon properties, Grüneisen parameters, scattering phase space and mechanical properties were all described in detail. We found that C14 performs well in heat transport; and via systematical comparison with another allotrope, diamond, its transport mechanism was further summarized. We hope the physical insights provided by this study could serve as theoretical support for nano-scale device design. [ABSTRACT FROM AUTHOR]

We report a strategy to use a fluorescence "turn on" sensor to quantify the reduction of platinum(IV) prodrugs in a real-time mode by simply and conveniently monitoring the fluorescence intensity. Proteins with high molecular weights, especially those between 10 and 100 kDa, contribute more to the reduction of the platinum(IV) complex in cell extracts. [ABSTRACT FROM AUTHOR]

Carboplatin-based platinum(IV) prodrugs containing axial carboxylates are relatively resistant to reduction to release active platinum(II) species and kill cancer cells. To facilitate the activation process, a boron dipyrromethene (BODIPY) ligand has been utilized as a photoabsorber at the axial position to photoactivate carboplatin-based platinum(IV) complexes. However, the influence of the axial ligands on the photoactivation rate of the platinum center and the subsequent biological activity are still unknown. In this study, we report the design and synthesis of a series of carboplatin-based photoactivable platinum(IV) prodrugs containing BODIPY axial ligands with different lengths. The resulting BODIPY-conjugated platinum(IV) prodrugs OH2C–OH8C bearing hydroxido ligands at the opposite axial position are slightly less stable in the dark than the corresponding prodrugs AC2C–AC8C containing acetato ligands. The prodrugs OH3C–OH8C can be photoactivated under irradiation in eight minutes, and the photoactivation rate is further improved in prodrugs AC3C–AC8C where only twenty seconds are needed. Moreover, the prodrug AC3C, in which the linker between the BODIPY photoabsorber and the platinum center has an appropriate length, is photoactivated the quickest among the acetylated prodrugs AC2C–AC8C. The high cellular accumulation may contribute more to the moderate photocytotoxicity of these prodrugs. Our research highlights the way to promote the photoactivation of BODIPY-conjugated platinum(IV) anticancer prodrugs by optimization of axial ligands and may contribute to the future rational design of photoactivable platinum-based complexes. [ABSTRACT FROM AUTHOR]

Layered double hydroxide (LDH) nanostructures and related nanocomposites have attracted significant interest in biomedical applications including cancer therapy, bioimaging and antibacterial treatment. These materials hold great advantages including low cost and facile preparation, convenient drug loading, high drug incorporation capacity, good biocompatibility, efficient intracellular uptake and endosome/lysosome escape, and natural biodegradability in an acidic environment. In this review, we summarize the development of three types of LDH nanostructures including pristine LDH, surface modified LDH, and LDH nanocomposites for a range of biomedical applications. The advantages and disadvantages of LDH nanostructures and insights into the future development are also discussed. [ABSTRACT FROM AUTHOR]

Cisplatin plays a pivotal role in the treatment of various malignant tumors, but its therapeutic effects are hampered by drug resistance. Pt(iv) prodrugs represent a promising class of “non-conventional” platinum-based anticancer agents to circumvent drug resistance, which can be easily functionalized with other bioactive ligands. One strategy is to build “dual-action” and “multi-action” Pt(iv) prodrugs that not only damage DNA but also perturb other pathways related to cisplatin resistance to achieve combinatorial therapeutic effects. Another way to overcome the shortcomings of cisplatin is to deliver Pt(iv) prodrugs via nanocarriers. Most studies in this area have focused on designing prodrugs based on the mechanism of cisplatin resistance within isolated cancer cells. Recent findings, however, reveal that the tumor microenvironment also plays important roles in the development of cisplatin resistance. This perspective focuses on various types of novel cisplatin-based Pt(iv) complexes, including Pt-loaded nanostructures, to overcome cisplatin resistance. Special attention will be devoted to complexes that target the tumor microenvironment, which is a new area for the development of effective Pt(iv) prodrugs. Our summary and outlook may have a hope to help researchers in the field generate new ideas and strategies to develop more potent Pt(iv) prodrugs to combat cisplatin resistance. [ABSTRACT FROM AUTHOR]

A copper(i)-mediated carboamination cascade reaction between vinyl azides and aryldiazonium salts is described. Functionally diverse N2-substituted 1,2,3-triazoles were obtained in moderate to good yields through novel difunctionalization of vinyl azides by aryldiazonium salt sources. This method has a wide scope, good functional-group tolerance and insensitivity to an ambient atmosphere. [ABSTRACT FROM AUTHOR]

In using nanomaterials for advanced photodynamic therapy, it is important to improve surface modification to increase stability, minimize non-specific loss of drugs in blood circulation, enhance the photostability of photosensitizers, and achieve highly efficient intracellular uptake. In this report, we for the first time covalently conjugate photosensitizer Chlorin e6 (Ce6) to polyethylene glycol modified layered double hydroxides and produce hybrid nanoflakes. These nanoflakes display many superior characteristics and lead to excellent in vivo photodynamic therapeutic efficiency and safety profiles. [ABSTRACT FROM AUTHOR]

A novel approach to design bimetallic anticancer drug candidates with the capability to combat both drug resistance and tumor metastasis is reported. These water-soluble bifunctional Pt(iv)–Ru(ii) heterodinuclear complexes with a unique mode of action display up to 2-orders of magnitude enhanced cytotoxicity in cisplatin-resistant cells and significantly impede cancer cell migration. [ABSTRACT FROM AUTHOR]

Platinum-based antineoplastic drugs are among the first-line chemotherapeutic agents against a variety of solid tumors, but toxic side-effects and drug resistance issues limit their clinical optimization. Novel strategies and platforms to conquer cisplatin resistance are highly desired. Herein, we assembled a multimodal nanoplatform utilizing 808 nm-excited and biocompatible core–shell–shell upconversion nanoparticles (UCNPs) [NaGdF4:Yb/Nd@NaGdF4:Yb/Er@NaGdF4] that were covalently loaded with not only photosensitizers (PSs), but also Pt(iv) prodrugs, which were rose bengal (RB) and c,c,t-[Pt(NH3)2Cl2(OCOCH2CH2NH2)2], respectively. The UCNPs had the capability to convert near infrared (NIR) light to visible light, which was further utilized by RB to generate singlet oxygen. At the same time, the nanoplatform delivered the Pt(iv) prodrug into cancer cells. Thus, this upconversion nanoplatform was able to carry out combined and simultaneous photodynamic therapy (PDT) and Pt chemotherapy. The nanoplatform was well characterized and the energy transfer efficiency was confirmed. Compared with free cisplatin or UCNPs loaded with RB only, our nanoplatform showed significantly improved cytotoxicity upon 808 nm irradiation in both cisplatin-sensitive and -resistant human ovarian cancer cells. A mechanistic study showed that the nanoparticles efficiently delivered the Pt(iv) prodrug into cancer cells, resulting in Pt-DNA damage, and that the nanoplatform generated cellular singlet oxygen to kill cancer cells. We, therefore, provide a comprehensive strategy to use UCNPs for combined Pt chemotherapy and PDT against cisplatin resistance, and our nanoplatform can also be used as a theranostic tool due to its NIR bioimaging capacity. [ABSTRACT FROM AUTHOR]

Platinum(iv)-based anticancer prodrugs have attracted much attention due to their relative inertness under physiological conditions, being activated inside cells, and their capacity for functionalization with a variety of small-molecule or macromolecule moieties. Novel asymmetric platinum(iv) compounds synthesized through expedient and unique methods are desired. Here we utilize N-bromosuccinimide (NBS) and carry out oxidative bromination on platinum(ii) drugs, namely cisplatin, carboplatin, and oxaliplatin, to obtain asymmetric and mono-bromo platinum(iv) prodrugs. Different solvents are used to obtain various compounds, and the compounds are further functionalized. Di-bromo compounds are also obtained through NBS-directed oxidative bromination in ethanol. The crystal structures of representative compounds are discussed, and the reduction potentials of some compounds are examined. A cytotoxicity test shows that the mono- and di-bromo platinum(iv) compounds are active against human ovarian cancer cells. Our study enriches the family of asymmetric platinum(iv) prodrugs and provides with a convenient strategy to obtain brominated platinum(iv) complexes. [ABSTRACT FROM AUTHOR]

A nanohybrid is assembled by ratiometrically co-loading Pt(iv) prodrugs and photosensitizers into layered double hydroxide nanoparticles. The nanohybrid shows synergistic cell-killing effects and is significantly active against the proliferation of cisplatin-resistant human cancer cells with nanomolar IC50 values. Profound mechanistic investigations confirm its action mode of combined chemo- and photodynamic therapy. [ABSTRACT FROM AUTHOR]

Upconversion nanoparticles capable of converting low-energy excitation into higher-energy emission have been proved to be useful for sensitive biodetection due to the largely eliminated background autofluorescence and light scattering effects. However, the existing techniques have been constrained due to the absorption of excitation and emission light by water and hemoglobin in biological settings that typically result in low light penetration depth and potential thermal damage to biological samples. In this work, a core–shell–shell nanostructure is described to realize photon upconversion in the first biological spectral window (650–900 nm) where the absorption of water and the biological specimen is minimal. We synthesized core–shell–shell nanoparticles with small feature size (∼30 nm) that display dominant emission in the far red (660 nm) spectral region upon excitation at 808 nm. The as-synthesized core–shell–shell nanoparticles were further developed as optical bioprobes that offer sensitive biodetection in the presence of tissue wrapping. [ABSTRACT FROM AUTHOR]

A nanoplatform targeting DNA and p53 simultaneously is assembled. Layered double hydroxide nanoparticles are co-loaded with a Pt(iv) prodrug and a p53 activator. Once inside cells, cisplatin is released to attack genomic DNA and kill cancer cells; simultaneously, the p53 activator results in active p53, a key protein involved in the apoptotic pathways initiated by platinum drugs. The anticancer efficacy of cisplatin is significantly improved through this synergistic application. [ABSTRACT FROM AUTHOR]

Complexation of cisplatin with a p53 activator as a single anticancer agent resulted in synergistically improved cytotoxicity in p53 wild-type but not p53 null human cancer cells. Mechanistic investigation was carried out on this dual-targeting Pt(iv) prodrug, chalcoplatin. The prodrug effectively entered cancer cells and arrested the cell cycle at the S and G2/M phases, distinctive of that from cisplatin. Chalcoplatin significantly induced p53 activation as well as the subsequent apoptosis pathways. This unique mode of action renders chalcoplatin remarkably cytotoxic and makes this compound among the first examples of a Pt(iv) prodrug that directly interacts with the downstream pathway after the formation of Pt–DNA lesions. [ABSTRACT FROM AUTHOR]

Enhanced selectivity and efficacy is important for advanced drug delivery. Herein, a novel type of folic acid conjugated self-assembled layered double hydroxide nanoparticles is reported. These nanoparticles have a drug loading capacity of 27 wt% and are able to enter cell nuclei and dramatically improve the efficacy of MTX. [ABSTRACT FROM AUTHOR]

Platinum-based drugs have revolutionized cancer chemotherapy; however, their therapeutic efficacy has been limited by severe side effects and drug resistance. Recently, approaches that target specific organelles in cancer cells have emerged as attractive alternatives to overcome these challenges. Many studies have validated these strategies and highlighted that organelle-targeted platinum complexes demonstrate increased anticancer activity, the ability to overcome drug resistance, novel molecular mechanisms, or even lower toxicity. This review provides a brief summary of various organelle-targeting strategies that promote the accumulation of platinum complexes in certain intracellular areas, such as the nucleus, mitochondria, endoplasmic reticulum (ER), and lysosomes. Moreover, the mechanisms through which these strategies improve anticancer performance, overcome drug resistance, and alter the action mode of conventional platinum drugs are discussed. By providing an extensive account of platinum complexes targeting different organelles, this review aims to assist researchers in understanding the design principles, identifying potential targets, and fostering innovative ideas for the development of platinum complexes., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Pt(IV) complexes bearing axial carbonate linkages have drawn much attention recently. A synthetic method behind this allows the hydroxyl group of bioactive ligands to be attached to the available hydroxyl group of Pt(IV) complexes, and the rapid release of free drugs is achieved after the reduction of carbonate-linked Pt(IV) complexes. Further understanding on the properties of Pt(IV) carbonates such as hydrolytic stability and reduction profiles, however, is hindered by limited research. Herein, six mono-carbonated Pt(IV) complexes in which the carbonate axial ligands possess various electron-withdrawing powers were synthesized, and the corresponding mono-carboxylated analogues were also prepared as references to highlight the different properties. The influence of the coordination environment towards the hydrolysis and reduction rate of Pt(IV) carbonates and carboxylates was explored. The mono-carbonated Pt(IV) complexes are both less stable and reduced faster than the corresponding mono-carboxylated ones. Moreover, the hydrolysis and reduction profiles are dependent not only on the electron-withdrawing ability of the carbonates but also on the nature of the opposite axial ligands. Besides, the exploration of the hydrolytic pathway for Pt(IV) carbonates suggests that the process proceeds by an attack of OH - on the carbonyl carbon, followed by elimination, which is different from that of Pt(IV) carboxylates. This study provides some information on the influence of axial carbonate ligands with different electron-withdrawing abilities on the properties of the Pt(IV) center, which may inspire new thoughts on the design of "multi-action" Pt(IV) prodrugs.

Carboplatin-based platinum(IV) prodrugs containing axial carboxylates are relatively resistant to reduction to release active platinum(II) species and kill cancer cells. To facilitate the activation process, a boron dipyrromethene (BODIPY) ligand has been utilized as a photoabsorber at the axial position to photoactivate carboplatin-based platinum(IV) complexes. However, the influence of the axial ligands on the photoactivation rate of the platinum center and the subsequent biological activity are still unknown. In this study, we report the design and synthesis of a series of carboplatin-based photoactivable platinum(IV) prodrugs containing BODIPY axial ligands with different lengths. The resulting BODIPY-conjugated platinum(IV) prodrugs OH2C-OH8C bearing hydroxido ligands at the opposite axial position are slightly less stable in the dark than the corresponding prodrugs AC2C-AC8C containing acetato ligands. The prodrugs OH3C-OH8C can be photoactivated under irradiation in eight minutes, and the photoactivation rate is further improved in prodrugs AC3C-AC8C where only twenty seconds are needed. Moreover, the prodrug AC3C, in which the linker between the BODIPY photoabsorber and the platinum center has an appropriate length, is photoactivated the quickest among the acetylated prodrugs AC2C-AC8C. The high cellular accumulation may contribute more to the moderate photocytotoxicity of these prodrugs. Our research highlights the way to promote the photoactivation of BODIPY-conjugated platinum(IV) anticancer prodrugs by optimization of axial ligands and may contribute to the future rational design of photoactivable platinum-based complexes.

Stable fluorescent silver nanoclusters (AgNCs) were synthesized through one-step UV photoreduction using the multiple carboxyl copolymer poly(methacrylic acid- co -itaconic acid) P(MAA- co -IA) as a novel template. The fluorescence lifetime and the quantum yield of the obtained AgNCs were 1.84 ns and 8.9% in an aqueous solution, respectively. Owing to the multiple carboxyls of the protective P(MAA- co -IA) template, the obtained AgNCs have excellent advantages such as good dispersity, and high stability, which make them suitable for highly sensitive and selective detection of Cu 2+ by fluorescence quenching. A good linear relationship exists between the degree of fluorescence quenching for silver nanoclusters and Cu 2+ concentration ranging from 0 to 10 μM. The limit of detection (LOD) is 6.36 nM. The result implies that the as-synthesized AgNCs show great potential in the analysis field., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Cisplatin plays a pivotal role in the treatment of various malignant tumors, but its therapeutic effects are hampered by drug resistance. Pt(iv) prodrugs represent a promising class of "non-conventional" platinum-based anticancer agents to circumvent drug resistance, which can be easily functionalized with other bioactive ligands. One strategy is to build "dual-action" and "multi-action" Pt(iv) prodrugs that not only damage DNA but also perturb other pathways related to cisplatin resistance to achieve combinatorial therapeutic effects. Another way to overcome the shortcomings of cisplatin is to deliver Pt(iv) prodrugs via nanocarriers. Most studies in this area have focused on designing prodrugs based on the mechanism of cisplatin resistance within isolated cancer cells. Recent findings, however, reveal that the tumor microenvironment also plays important roles in the development of cisplatin resistance. This perspective focuses on various types of novel cisplatin-based Pt(iv) complexes, including Pt-loaded nanostructures, to overcome cisplatin resistance. Special attention will be devoted to complexes that target the tumor microenvironment, which is a new area for the development of effective Pt(iv) prodrugs. Our summary and outlook may have a hope to help researchers in the field generate new ideas and strategies to develop more potent Pt(iv) prodrugs to combat cisplatin resistance.

A copper(i)-mediated carboamination cascade reaction between vinyl azides and aryldiazonium salts is described. Functionally diverse N 2 -substituted 1,2,3-triazoles were obtained in moderate to good yields through novel difunctionalization of vinyl azides by aryldiazonium salt sources. This method has a wide scope, good functional-group tolerance and insensitivity to an ambient atmosphere.

Platinum-based antineoplastic drugs are among the first-line chemotherapeutic agents against a variety of solid tumors, but toxic side-effects and drug resistance issues limit their clinical optimization. Novel strategies and platforms to conquer cisplatin resistance are highly desired. Herein, we assembled a multimodal nanoplatform utilizing 808 nm-excited and biocompatible core-shell-shell upconversion nanoparticles (UCNPs) [NaGdF4:Yb/Nd@NaGdF4:Yb/Er@NaGdF4] that were covalently loaded with not only photosensitizers (PSs), but also Pt(iv) prodrugs, which were rose bengal (RB) and c,c,t-[Pt(NH3)2Cl2(OCOCH2CH2NH2)2], respectively. The UCNPs had the capability to convert near infrared (NIR) light to visible light, which was further utilized by RB to generate singlet oxygen. At the same time, the nanoplatform delivered the Pt(iv) prodrug into cancer cells. Thus, this upconversion nanoplatform was able to carry out combined and simultaneous photodynamic therapy (PDT) and Pt chemotherapy. The nanoplatform was well characterized and the energy transfer efficiency was confirmed. Compared with free cisplatin or UCNPs loaded with RB only, our nanoplatform showed significantly improved cytotoxicity upon 808 nm irradiation in both cisplatin-sensitive and -resistant human ovarian cancer cells. A mechanistic study showed that the nanoparticles efficiently delivered the Pt(iv) prodrug into cancer cells, resulting in Pt-DNA damage, and that the nanoplatform generated cellular singlet oxygen to kill cancer cells. We, therefore, provide a comprehensive strategy to use UCNPs for combined Pt chemotherapy and PDT against cisplatin resistance, and our nanoplatform can also be used as a theranostic tool due to its NIR bioimaging capacity.

Platinum(IV)-based anticancer prodrugs have attracted much attention due to their relative inertness under physiological conditions, being activated inside cells, and their capacity for functionalization with a variety of small-molecule or macromolecule moieties. Novel asymmetric platinum(IV) compounds synthesized through expedient and unique methods are desired. Here we utilize N-bromosuccinimide (NBS) and carry out oxidative bromination on platinum(II) drugs, namely cisplatin, carboplatin, and oxaliplatin, to obtain asymmetric and mono-bromo platinum(IV) prodrugs. Different solvents are used to obtain various compounds, and the compounds are further functionalized. Di-bromo compounds are also obtained through NBS-directed oxidative bromination in ethanol. The crystal structures of representative compounds are discussed, and the reduction potentials of some compounds are examined. A cytotoxicity test shows that the mono- and di-bromo platinum(IV) compounds are active against human ovarian cancer cells. Our study enriches the family of asymmetric platinum(IV) prodrugs and provides with a convenient strategy to obtain brominated platinum(IV) complexes.

Complexation of cisplatin with a p53 activator as a single anticancer agent resulted in synergistically improved cytotoxicity in p53 wild-type but not p53 null human cancer cells. Mechanistic investigation was carried out on this dual-targeting Pt(IV) prodrug, chalcoplatin. The prodrug effectively entered cancer cells and arrested the cell cycle at the S and G2/M phases, distinctive of that from cisplatin. Chalcoplatin significantly induced p53 activation as well as the subsequent apoptosis pathways. This unique mode of action renders chalcoplatin remarkably cytotoxic and makes this compound among the first examples of a Pt(IV) prodrug that directly interacts with the downstream pathway after the formation of Pt-DNA lesions.

Providing strategies to overcome the toxicity and side effects of platinum-based antineoplastic drugs is crucial for their future development. Here we describe a strategy of using low-cytotoxic and non-functionalized layered double hydroxide (LDH) nanoparticles (NPs) to increase the cancer-cell specificity as well as anticancer efficacy of a cisplatin prodrug. In our study, the prodrug is efficiently loaded into and protected by LDH. The Pt-loaded NPs exhibit much higher cytotoxicity than the prodrug against cancer cells. Moreover, the Pt-loaded NPs are much less active against certain types of normal cells. We further investigate the mechanisms behind these phenomena including cellular uptake, cell cycle arrest, and apoptosis induction. We find that LDH is able to significantly improve both the cellular uptake of Pt and genomic DNA platination in cancer cells, and the Pt-loaded NPs induce severe apoptosis in cancer but not normal cells. All of these findings imply that Pt-loaded LDH NPs have great potential to be further developed as anticancer nanomedicine.

Dissolving polymer microneedles have attracted much attention for their biocompatibility, fast dissolution, and high drug loading. Among them, polyvinylpyrrolidone (PVP) is widely used, but its high water absorption and poor mechanical properties constrain its broad applications. Herein we show that adding cyclodextrin (CD) to form PVP-CD inclusion complexes can alleviate these problems. The water absorption of PVP was reduced by 36-40% at different RHs as the PVP-CD inclusion complexes formed. Attractively, the water absorption at 10 and 20 days remained almost the same for the complexes while it could dramatically increase for the pure PVP samples, particularly in high humidity environments, indicating a possibly longer storage time for the complexes. It was also found that the Young's modulus and hardness of the PVP-CD could be greatly improved, especially for low molecular weight PVP. Furthermore, the glass transition temperature (T g ) of the PVP-CD increased by up to 39 °C. With the improved properties, the fabricated PVP-CD microneedles possessed much sharper needle tips and the patch had less cracks than those made from pure PVP. Pig skin application results suggested that the PVP-CD microneedle arrays were able to reliably pierce the stratum corneum of the skin while it was not achievable for the PVP microneedles with the same geometry. We anticipate that these PVP-CD complex microneedles are more suitable for vaccine and drug delivery because of their superior properties.