A Polymeric Nanoparticle to Co-Deliver Mitochondria-Targeting Peptides and Pt(IV) Prodrug: Toward High Loading Efficiency and Combination Efficacy.

Developing combination chemotherapy systems with high drug loading efficiency at predetermined drug ratios to achieve a synergistic effect is important for cancer therapy. Herein, a polymeric dual-drug nanoparticle composed of a Pt(IV) prodrug derived from oxaliplatin and a mitochondria-targeting cytotoxic peptide is constructed through emulsion interfacial polymerization, which processes high drug loading efficiency and high biocompatibility. The depolymerization of polymeric dual-drug nanoparticle and the activation of Pt prodrug can be effectively triggered by the acidic tumor environment extracellularly and the high levels of glutathione intracellularly in cancer cells, respectively. The utilization of mitochondria-targeting peptide can inhibit ATP-dependent processes including drug efflux and DNA damage repair. This leads to increased accumulation of Pt-drugs within cancer cells. Eventually, the polymeric dual-drug nanoparticle demonstrates appreciable antitumor effects on both cell line derived and patient derived xenograft lung cancer model. It is highly anticipated that the polymeric dual-or multi-drug systems can be applied for combination chemotherapy to achieve enhanced anticancer activity and reduced side effects.

Near-Infrared-I to III Absorption and Emission via Core Engineering of Open-Shelled Organic Mixed-Valence Systems.

A novel class of agents is developed based on the core engineering of open-shelled organic mixed-valence (MV) systems, which enable tunable absorption and emission across the near infrared (NIR)-I to III biowindow (700-1850 nm) by adjusting the number of central nitrogen oxidation sites and the length of the conjugated bridge. Organic mixed-valence (MV) systems are synthesized through a one-step partial chemical oxidation of starburst oligoarylamines, with varying nitrogen oxidation sites and conjugated bridge lengths, including tris(4-[diethylamino]phenyl)aminen+ (T4EPAn + ), N,N,N',N'-tetrakis(4-[diisobutylamino]phenyl)-1,4-phenylenediaminen+ (TPDAn + ), and N,N,N',N'-tetrakis(4-methoxyphenyl)benzidinen+ (TMPBn + ). The absorption wavelength of the MV systems redshifted clearly as the number of central nitrogen oxidation sites increased or the conjugated bridge length is prolonged. T4EPAn + with one central nitrogen oxidation site exhibits fluorescence emission in the range of 900-1400 nm, while TPDAn + with two central nitrogen oxidation sites demonstrate strong heat generation capabilities. Additionally, the absorption peak of TMPBn + with a biphenyl conjugated bridge reaches up to 1610 nm. Especially, these MV systems are highly stable for biological applications due to their high steric hindrance and hyperconjugation effect. These characteristics make MV systems promising candidates for constructing NIR-I/II/III emitters and photothermal agents, representing a significant advance toward developing the next generation of NIR-I to III agents.

Transforming Cold Tumors into Hot Ones with a Metal-Organic Framework-Based Biomimetic Nanosystem for Enhanced Immunotherapy.

Immunotherapy has revolutionized the landscape in clinical tumor therapy, although the response rates in "cold" tumors are relatively low owing to the complex tumor microenvironment (TME). Cyclic guanosine monophosphate-adenosine monophosphate synthase/stimulator of interferon genes (cGAS/STING) pathway-inducing agents can reprogram the TME; however, their applications remain underutilized. Herein, we engineered a facile manganese-based metal-organic framework (Mn-MOF) encapsulating polyphyllin I (PPI) and coated it with red blood cell (RBC) membranes (RBC@Mn-MOF/PPI) that enhanced the cGAS/STING-mediated antitumor immunity. RBC@Mn-MOF/PPI was engineered by camouflaging it with a biomimetic RBC membrane for prolonged blood circulation and immune escape, which was also extended with TME-sensitive properties for triggering the release of PPI and Mn2+ to remodel the suppressive TME and augment antitumor immune responses. Furthermore, RBC@Mn-MOF/PPI helped transform cold tumors into "hot" ones by activating immune cells, as evidenced via dendritic cell maturation, cytotoxic T lymphocyte infiltration, and natural killer cell recruitment, thereby targeting primary and abscopal tumors and lung metastatic nodules. Therefore, our engineered nanosystem represents a novel strategy to transform immunologically "cold" tumors into "hot" ones by activating the cGAS/STING pathway, thereby addressing the major challenges associated with immunotherapy.

NIR-II Fluorescent Probe for Detecting Trimethylamine Based on Intermolecular Charge Transfer.

A new kind of small organic NIR-II fluorophore molecule (ZS-1010) based on intermolecular charge transfer was developed as a NIR-II fluorescent probe for trimethylamine (TMA) detection, which is important for the diagnosis of cardiovascular disease, chronic kidney disease and diabetes. ZS-1010 has a strong push-pull electron system composed of electron donor unit and electron acceptor unit, exhibiting strong absorption and emission in the NIR-II region. When mixed with TMA which possesses strong electron-donating characteristics, the push-pull system of ZS-1010 will be affected along with the dipole moment change, leading to the quenching of fluorescence. This is the first example of TMA fluorescent probe in the NIR-II window showing deep penetration, fast response speed, high selectivity and pH stability.

Macrocyclic Photoinitiator Based on Prism[5]arene Matching LEDs Light with Low Migration.

In this work, a naphthalene-based macrocycle prism[5]arene (NP5 OCH3 ) is developed as a novel kind of photoinitiator. When NP5 OCH3 is irradiated under light, the bond between methylene and naphthalene can be quickly broken owning to the existence of ring tension. The macrocycle is cleaved to linear oligomer biradicals, which can effectively initiate the free radical photopolymerization of acrylate monomers. Compared with conventional photoinitiators, NP5 OCH3 has strong light absorption in the wavelength range of 365-405 nm, so it can well match the environment-friendly light-emitting diodes (LEDs) light source to realize highly efficient initiation. In addition, there is no small molecule fragment generated during NP5 OCH3 fracture, and the resulted linear oligomer biradicals can be immobilized in the polymer after initiating polymerization, so NP5 OCH3 photoinitiators show much lower migration rate and cytotoxicity. Cleavable macrocycle prismarene may provide a new idea for the design of safe and efficient photoinitiators matching long wavelength light.

Pillar[6]arene: Light Cleaves Macrocycle to Linear Oligomer Biradical to Initiate Photopolymerization.

A novel kind of photoinitiator based on the macrocyclic molecule pillar[6]arene (P6OC2H5) is reported. Under light irradiation, P6OC2H5 was cleaved to a linear oligomer biradical, which could efficiently initiate free-radical photopolymerization. Owing to the absence of small molecular fragment generation, the macrocyclic photoinitiator exhibited a much lower migration rate and cytotoxicity than commercial photoinitiators. This is the first time that a macrocyclic molecule has been developed as a photoinitiator based on the macrocycle fracture mechanism.

Controllable Release Mode Based on ATP Hydrolysis-Fueled Supra-Amphiphile Assembly.

The controllable intermittent and stepwise release modes were achieved in a dissipative system of supra-amphiphile. The supra-amphiphile was constructed based on complexation of cationic amphiphile (Zn@DPA-14) and biological energy currency, adenosine triphosphate (ATP). The formation of supra-amphiphile and the competing hydrolysis of ATP by enzyme drove the micelles assembled by Zn@DPA-14 away from the thermodynamic equilibrium state, leading to the cargo release from micelles during the process of micelles transformed to vesicles. Following the time-dependent evolution, the intermittent release or stepwise release modes of the loaded cargo realized through adjusting the polarity of the cargo molecules. The strategy advancing from "traditional" release modes under thermodynamic control toward the life-like controllable modes in the far-from-equilibrium state shows unique potential applications on transport vehicles and biomedical field.

Charge-reversal surfactant antibiotic material for reducing microbial corrosion in petroleum exploitation and transportation.

The corrosions caused by sulfate-reducing bacteria (SRB) are serious problems in petroleum exploitation and transportation, which can lead to safety problems, environmental pollutions, and economic losses. Here, a charge-reversal surfactant antibiotic material N-dodecyl-1-carboxylic acid-1-cyclohexenyl-2-carboxamide (C12N-DCA) is designed and synthesized. C12N-DCA is a negatively charged surfactant, which cannot be adsorbed by soil and rock in a large amount. Therefore, it can reach the "lesion location", with enough concentration. After being hydrolyzed and charge reversed under the acceleration of H2S produced by SRB, C12N-DCA becomes a positively charged surfactant dodecane ammonium salt to kill SRB. Through a simulating experiment, it is found that C12N-DCA can reach the SRB inhibition ratio of almost 100%, and it can reduce iron corrosion by 88%. Such an antibiotic material or its homologs may be added to the chemical flooding fluids, killing SRB during petroleum exploitation and reducing the SRB-induced corrosion in the petroleum exploitation and transportation.

A Supramolecular Radical Dimer: High-Efficiency NIR-II Photothermal Conversion and Therapy.

Photothermal therapy at the NIR-II biowindow (1000-1350 nm) is drawing increasing interest because of its large penetration depth and maximum permissible exposure. Now, the supramolecular radical dimer, fabricated by N,N'-dimethylated dipyridinium thiazolo[5,4-d]thiazole radical cation (MPT.+ ) and cucurbit[8]uril (CB[8]), achieves strong absorption at NIR-II biowindow. The supramolecular radical dimer (2MPT.+ -CB[8]) showed highly efficient photothermal conversion and improved stability, thus contributing to the strong inhibition on HegG2 cancer cell under 1064 nm irradiation even penetrating through chicken breast tissue. This work provides a novel approach to construct NIR-II chromophore by tailor-made assembly of organic radicals. It is anticipated that this study provides a new strategy to achieve NIR-II photothermal therapy and holds promises in luminescence materials, optoelectronic materials, and also biosensing.

Targeting the Cell Membrane by Charge-Reversal Amphiphilic Pillar[5]arene for the Selective Killing of Cancer Cells.

A charge-reversal amphiphilic pillar[5]arene, P5NH-DCA, bearing 10 charge-reversal headgroups is reported. It targets the cell membrane of cancer cells and selectively destroys the cancer cells by disrupting the membrane. In the acidic tumor microenvironment, the headgroup charge of P5NH-DCA reversed from negative to positive owing to hydrolysis of the acid-labile amide group. The hydrolyzed product bearing multiple positive charges can bind to the cell membrane and then disrupt the membrane of cancer cells with high efficiency. However, under the neutral microenvironment of healthy cells, the negatively charged P5NH-DCA remains stable and the cytotoxicity is considerably reduced. The strategy killing the cancer cells by membrane disruption may represent a new route of cancer chemotherapy.

A multifunctional supramolecular vesicle based on complex of cystamine dihydrochloride capped pillar[5]arene and galactose derivative for targeted drug delivery.

Background: Supramolecular vesicles are a novel class of nanocarriers that have great potential in biomedicine.Methods: A multifunctional supramolecular vesicle (CAAP5G) based on the complex of CAAP5 and galactose derivative (G) assembled via host-guest interaction was constructed. Results: Using Human embryonic kidney T (293T) cells as experimental models, the cytotoxic effects of CAAP5G was investigated to 0-50 µmol/L for 24 h. Notably, the CAAP5G vesicles revealed low-toxicity to 293T cells, it was critical to designing drug nano-carriers. Simultaneously, we have evaluated doxorubicin hydrochloride (DOX)-loaded CAAP5G vesicles anticancer efficiency, where DOX-loaded CAAP5G vesicles and free DOX incubated with Human hepatocellular carcinoma cancer cell (HpeG2 cells) and 293T cells for 24 h, 48 h, 72 h. It turned out that CAAP5G vesicles encapsulated anticancer drug (DOX) could decrease DOX side-effect on 293T cells and increase DOX anticancer efficiency. More importantly, the cysteamine as an adjuvant chemotherapy drug was released from CAAP5G vesicles in HepG2 cells where a higher GSH concentration exists. The adjuvant chemotherapy efficiency was evaluated, where free DOX and DOX-loaded CAAP5G vesicles incubated with DOX-resistance HepG2 cells (HepG2-ADR cells) for 24, 48, 72 h, respectively. Conclusion: The results revealed that the DOX encapsulated by CAAP5G vesicles could enhance the cytotoxicity of DOX and provide insights for designing advanced nano-carriers toward adjuvant chemotherapies.

Molecular engineering of polymeric supra-amphiphiles.

Polymeric supra-amphiphiles are amphiphiles that are fabricated by linking polymeric segments, or small molecules and polymeric segments, by noncovalent interactions or dynamic covalent bonds. Compared with conventional amphiphilic polymers, polymeric supra-amphiphiles are advantageous in that they possess dynamic features and their preparation may be to some extent more facile. Moreover, polymeric supra-amphiphiles are endowed with richer structure and higher stability compared with small-molecule supra-amphiphiles. Owing to these properties, polymeric supra-amphiphiles have so far shown great promise as surfactants, nanocarriers and in therapies. In this tutorial review, recent work on polymeric supra-amphiphiles, from molecular architectures to functional assemblies, is presented and summarized. Different polymeric supra-amphiphile topologies and related applications are highlighted. By combining polymer chemistry with supramolecular chemistry and colloid science, we anticipate that the study of polymeric supra-amphiphiles will promote the continued development of the molecular engineering of functional supramolecular systems, and lead to practical applications, especially in drug delivery.

pH-Induced Charge-Reversal Amphiphile with Cancer Cell-Selective Membrane-Disrupting Activity.

A charge-reversal amphiphile exhibiting charge conversion from negative to positive induced by pH is reported. It selectively kills cancer cells through cell membrane disruption. This amphiphile comprising an alkyl chain and anionic headgroup of acid-labile ß-carboxylic amide (C16N-DCA) was prepared. In the microenvironment of normal cells with pH 7.4, the negatively charged C16N-DCA exhibited considerably reduced cytotoxicity. However, in the acidic microenvironment of cancer cells with pH 6.5-6.8, the headgroup charge of C16N-DCA changed from negative to positive under hydrolysis of the acid-labile amide group. As a result, the generated cationic amphiphile displayed significant killing of cancer cells by disrupting their cell membranes. Such pH-selective cell killing bioactivity represents a new route of chemotherapy for anticancer strategies.

Multifunctional supramolecular vesicles based on the complex of ferrocenecarboxylic acid capped pillar[5]arene and a galactose derivative for targeted drug delivery.

Supramolecular vesicles based on the host-guest complexation of ferrocenecarboxylic acid capped pillar[5]arene and a galactose derivative have been constructed, which showed dual-responsiveness and cancer cells targetability resulting from its ferrocenecarboxylic acid units and galactose units, respectively. This work provides a good example for the construction of multifunctional nanocarriers for targeted drug delivery.

Cationic vesicles based on amphiphilic pillar[5]arene capped with ferrocenium: a redox-responsive system for drug/siRNA co-delivery.

A novel ferrocenium capped amphiphilic pillar[5]arene (FCAP) was synthesized and self-assembled to cationic vesicles in aqueous solution. The cationic vesicles, displaying low cytotoxicity and significant redox-responsive behavior due to the redox equilibrium between ferrocenium cations and ferrocenyl groups, allow building an ideal glutathione (GSH)-responsive drug/siRNA co-delivery system for rapid drug release and gene transfection in cancer cells in which higher GSH concentration exists. This is the first report of redox-responsive vesicles assembled from pillararenes for drug/siRNA co-delivery; besides enhancing the bioavailability of drugs for cancer cells and reducing the adverse side effects for normal cells, these systems can also overcome the drug resistance of cancer cells. This work presents a good example of rational design for an effective stimuli-responsive drug/siRNA co-delivery system.

Bis(µ-3-nitro-benzene-1,2-dicarboxyl-ato)-κ(4)O(1),O(2):O(1),O(1');κ(4)O(1),O(1'):O(1),O(2)-bis-[triaqua-(6-carb-oxy-2-nitro-benzoato-κ(2)O(1),O(6))neodymium(III)] dihydrate.

The title complex, [Nd(2)(C(8)H(3)NO(6))(2)(C(8)H(4)NO(6))(2)(H(2)O)(6)]·2H(2)O, consists of dimeric units related by an inversion center. The Nd(III) atom is nine-coordinated by three O atoms from water mol-ecules and six from carboxyl-ate atoms. The 1,2-dicarboxylate acid molecules are in a single and double deprotonation stage and exhibit two coord-in-ation modes, viz. µ(2)-(κ(4), O(1): O(2): O(2): O(3)) and µ(1)-(κ(2), O(2): O(3)), which are responsible for the dimeric structure framework. The dimeric structure is then assembled into a three-dimensional supramolecular framework via O-H⋯O hydrogen bonds.