Platelet‐Inspired Nanocells for Targeted Heart Repair After Ischemia/Reperfusion Injury

Cardiovascular disease is the leading cause of mortality worldwide. While reperfusion therapy is vital for patient survival post‐heart attack, it also causes further tissue injury, known as myocardial ischemia/reperfusion (I/R) injury in clinical practice. Exploring ways to attenuate I/R injury is of clinical interest for improving post‐ischemic recovery. A platelet‐inspired nanocell (PINC) that incorporates both prostaglandin E2 (PGE₂)‐modified platelet membrane and cardiac stromal cell‐secreted factors to target the heart after I/R injury is introduced. By taking advantage of the natural infarct‐homing ability of platelet membrane and the overexpression of PGE₂ receptors (EPs) in the pathological cardiac microenvironment after I/R injury, the PINCs can achieve targeted delivery of therapeutic payload to the injured heart. Furthermore, a synergistic treatment efficacy can be achieved by PINC, which combines the paracrine mechanism of cell therapy with the PGE₂/EP receptor signaling that is involved in the repair and regeneration of multiple tissues. In a mouse model of myocardial I/R injury, intravenous injection of PINCs results in augmented cardiac function and mitigated heart remodeling, which is accompanied by the increase in cycling cardiomyocytes, activation of endogenous stem/progenitor cells, and promotion of angiogenesis. This approach represents a promising therapeutic delivery platform for treating I/R injury.     

Cancer Cell Membrane‐Coated Nanoparticles for Personalized Therapy in Patient‐Derived Xenograft Models

Cell membrane coating nanotechnology, which endows nanoparticles with unique properties, displays excellent translational potential in cancer diagnosis and therapy. However, the preparation and evaluation of these cell membrane‐coated nanoparticles are based on cell lines and cell‐line‐based xenograft mouse models. The feasibility of cell membrane‐camouflaged nanomaterials is tested in a preclinical setting. Head and neck squamous cell carcinoma (HNSCC) patient‐derived tumor cell (PDTC) membranes are coated onto gelatin nanoparticles (GNPs) and the resulting PDTC@GNPs show efficient targeting to homotypic tumor cells and tissues in patient‐derived xenograft (PDX) models. When the donor‐derived cell membrane of PDTC@GNPs matched those of the host cells, significant targeting capability is observed. In contrast, mismatch between the donor and host results in weak targeting. Furthermore, it is demonstrated that autologous separation and administration of cellular membranes and anticancer cisplatin (Pt)‐loaded PDTC@GNPs, respectively, lead to almost complete tumor ablation in a subcutaneous model and effectively inhibit tumor recurrence in a postsurgery model. The work presented here reinforces the translation of these biomimetic nanoparticles for clinical applications and offers a simple, safe, and effective strategy for personalized cancer treatment.     

Myeloid‐Derived Suppressor Cell Membrane‐Coated Magnetic Nanoparticles for Cancer Theranostics by Inducing Macrophage Polarization and Synergizing Immunogenic Cell Death

A major challenge for traditional cancer therapy, including surgical resection, chemoradiotherapy, and immunotherapy, is how to induce tumor cell death and leverage the host immune system at the same time. Here, a myeloid‐derived suppressor cell (MDSC) membrane‐coated iron oxide magnetic nanoparticle (MNP@MDSC) to overcome this conundrum for cancer therapy is developed. In this study, MNP@MDSC demonstrates its superior performance in immune evasion, active tumor‐targeting, magnetic resonance imaging, and photothermal therapy (PTT)‐induced tumor killing. Compared with red blood cell membrane‐coated nanoparticles (MNPs@RBC) or naked MNPs, MNP@MDSCs are much more effective in active tumor‐targeting, a beneficial property afforded by coating MNP with membranes from naturally occurring MDSC, thus converting the MNP into “smart” agents that like to accumulate in tumors as the source MDSCs. Once targeted to the tumor microenvironment, MNPs@MDSC can act as a PTT agents for enhanced antitumor response by inducing immunogenic cell death, reprogramming the tumor infiltrating macrophages, and reducing the tumor's metabolic activity. These benefits, in combination with the excellent biocompatibility and pharmacological kinetics characteristics, make MNP@MDSC a promising, multimodal agent for cancer theranostics.     

A Charge Reversible Self‐Delivery Chimeric Peptide with Cell Membrane‐Targeting Properties for Enhanced Photodynamic Therapy

The cell membrane is the most important protective barrier in living cells and cell membrane targeted therapy may be a high‐performance therapeutic modality for tumor treatment. Here, a novel charge reversible self‐delivery chimeric peptide C₁₆–PRP–DMA is developed for long‐term cell membrane targeted photodynamic therapy (PDT). The self‐assembled C₁₆–PRP–DMA nanoparticles can effectively target to tumor by enhanced permeability and retention effect without additional carriers. After undergoing charge reverse in acidic tumor microenvironment, C₁₆–PRP–DMA inserts into the tumor cell membrane with a long retention time of more than 14 h, which is very helpful for in vivo applications. It is found that under light irradiation, the reactive oxygen species generated by the inserted C₁₆–PRP–DMA would directly disrupt cell membrane and rapidly induce cell necrosis, which remarkably increases the PDT effect in vitro and in vivo. This novel self‐delivery chimeric peptide with a long‐term cell membrane targeting property provides a new prospect for effective PDT of cancer.     

Development of a Dual‐Modally Traceable Nanoplatform for Cancer Theranostics Using Natural Circulating Cell‐Derived Microparticles in Oral Cancer Patients

Cell‐derived microparticles (MPs), which are biogenic nanosized membrane vesicles that convey bioactive molecules between cells, have exhibited great potential to serve as therapeutic platforms. However, so far, all the MPs used as theranostic vectors in previous studies have been produced in vitro from cell culture supernatants, which is still associated with several concerns regarding practical applications. In this study, circulating MPs (CMPs), which are freshly purified from the peripheral blood of oral squamous cell carcinoma (OSCC) patients, are directly and efficiently embedded with ultrasmall near‐infrared‐fluorescent magnetic quantum dots (Ag₂Se@Mn QDs) via electroporation. By virtue of the superior photostability, favorable biocompatibility, and dual‐mode traceability of Ag₂Se@Mn QD‐labeled CMPs in vivo, the tissue distribution and natural tumor‐targeting behavior of CMPs from OSCC patients are directly visualized in living mice for the first time. Moreover, by simultaneously embedding antitumor siRNA and Ag₂Se@Mn QDs into CMPs derived from OSCC patients, a dual‐modally traceable and actively tumor‐targeted nanoplatform for cancer theranostics is developed. This study reports the first reliable conjugation‐free labeling strategy for in vivo dual‐mode tracking of CMPs harvested from the human body, and, more importantly, reports the development of traceable tumor‐targeted theranostic vectors based on naturally occurring CMPs from cancer patients.     

Real‐Time Imaging Tracking of Engineered Macrophages as Ultrasound‐Triggered Cell Bombs for Cancer Treatment

Cell‐based drug delivery systems are a promising platform for tumor‐targeted therapy due to their high drug‐loading capacities and inherent tumor‐homing abilities. However, the real‐time tracking of these carrier cells and controlled release of the encapsulated drugs are still challenging. Here, ultrasound‐activatable cell bombs are developed by encapsulating doxorubicin (DOX) and phase transformable perfluoropentane (PFP) into hollow mesoporous organosilica nanoparticles (HMONs) to prepare DOX/PFP‐loaded HMONs (DPH), followed by internalization into macrophages (RAW 264.7 cells). The resulting cell bombs (DPH‐RAWs) can maintain viability and actively home to the tumor. Especially, their migration can be tracked in real time using ultrasound due to the vaporization of a small portion of PFP during cell incubation at 37 °C. After accumulation at the tumor site, the further vaporization of remaining PFP can be triggered by a short‐pulsed high intensity focused ultrasound (HIFU) sonication, resulting in the generation of several large microbubbles, which destroys DPH‐RAWs and allows drug release out of these cells. The DPH‐RAWs combined with short‐pulsed HIFU sonication significantly inhibit tumor growth and prolong survival of tumor‐bearing mice. In conclusion, this study provides a new approach to cell‐based drug delivery systems for real‐time tracking of their migration and targeted cancer treatment.     

A Multi‐Gradient Targeting Drug Delivery System Based on RGD‐l‐TRAIL‐Labeled Magnetic Microbubbles for Cancer Theranostics

The accurately and efficiently targeted delivery of therapeutic/diagnostic agents into tumor areas in a controllable fashion remains a big challenge. Here, a novel cancer targeting magnetic microbubble is elaborately fabricated. First, the γ‐Fe₂O₃ magnetic iron oxide nanoparticles are optimized to chemically conjugate on the surface of polymer microbubbles. Then, arginine‐glycine‐aspartic acid‐l ‐tumor necrosis factor‐related apoptosis‐inducing ligand (RGD‐l ‐TRAIL), antitumor targeting fusion protein, is precisely conjugated with magnetic nanoparticles of microbubbles to construct RGD molecularly targeted magnetic microbubble, which is defined as RGD‐l ‐TRAIL@MMBs. Such RGD‐l ‐TRAIL@MMBs is endowed with the multigradient cascade targeting ability following by magnetic targeting, RGD, as well as enhanced permeability and retention effect regulated targeting to result in high cancerous tissue targeting efficiency. Due to the highly specific accumulation of RGD‐l ‐TRAIL@MMBs in the tumor, the accurate diagnostic information of tumor can be obtained by dual ultrasound and magnetic resonance imaging. After imaging, the TRAIL molecules as anticancer agent also get right into the cancer cells by nanoparticle‐ and RGD‐mediated endocytosis to effectively induce the tumor cell apoptosis. Therefore, RGD‐l ‐TRAIL conjugated magnetic microbubbles could be developed as a molecularly targeted multimodality imaging delivery system with the addition of chemotherapeutic cargoes to improve cancer diagnosis and therapy.     

Charge‐Reversal Drug Conjugate for Targeted Cancer Cell Nuclear Drug Delivery

DNA‐toxin anticancer drugs target nuclear DNA or its associated enzymes to elicit their pharmaceutical effects, but cancer cells have not only membrane‐associated but also many intracellular drug‐resistance mechanisms that limit their nuclear localization. Thus, delivering such drugs directly to the nucleus would bypass the drug‐resistance barriers. The cationic polymer poly(L ‐lysine) (PLL) is capable of nuclear localization and may be used as a drug carrier for nuclear drug delivery, but its cationic charges make it toxic and cause problems in in‐vivo applications. Herein, PLL is used to demonstrate a pH‐triggered charge‐reversal carrier to solve this problem. PLL's primary amines are amidized as acid‐labile β‐carboxylic amides (PLL/amide). The negatively charged PLL/amide has a very low toxicity and low interaction with cells and, therefore, may be used in vivo. But once in cancer cells' acidic lysosomes, the acid‐labile amides hydrolyze into primary amines. The regenerated PLL escapes from the lysosomes and traverses into the nucleus. A cancer‐cell targeted nuclear‐localization polymer–drug conjugate has, thereby, been developed by introducing folic‐acid targeting groups and an anticancer drug camptothecin (CPT) to PLL/amide (FA‐PLL/amide‐CPT). The conjugate efficiently enters folate‐receptor overexpressing cancer cells and traverses to their nuclei. The CPT conjugated to the carrier by intracellular cleavable disulfide bonds shows much improved cytotoxicity.     

Multifunctional Mesoporous Silica Nanoparticles for Cancer‐Targeted and Controlled Drug Delivery

Multifunctional mesoporous silica nanoparticles are developed in order to deliver anticancer drugs to specific cancer cells in a targeted and controlled manner. The nanoparticle surface is functionalized with amino‐β‐cyclodextrin rings bridged by cleavable disulfide bonds, blocking drugs inside the mesopores of the nanoparticles. Poly(ethylene glycol) polymers, functionalized with an adamantane unit at one end and a folate unit at the other end, are immobilized onto the nanoparticle surface through strong β‐cyclodextrin/adamantane complexation. The non‐cytotoxic nanoparticles containing the folate targeting units are efficiently trapped by folate‐receptor‐rich HeLa cancer cells through receptormmediated endocytosis, while folate‐receptor‐poor human embryonic kidney 293 normal cells show much lower endocytosis towards nanoparticles under the same conditions. The nanoparticles endocytosed by the cancer cells can release loaded doxorubicin into the cells triggered by acidic endosomal pH. After the nanoparticles escape from the endosome and enter into the cytoplasm of cancer cells, the high concentration of glutathione in the cytoplasm can lead to the removal of the β‐cyclodextrin capping rings by cleaving the pre‐installed disulfide bonds, further promoting the release of doxorubicin from the drug carriers. The high drug‐delivery efficacy of the multifunctional nanoparticles is attributed to the co‐operative effects of folate‐mediated targeting and stimuli‐triggered drug release. The present delivery system capable of delivering drugs in a targeted and controlled manner provides a novel platform for the next generation of therapeutics.     

Simple and Efficient Targeted Intracellular Protein Delivery with Self‐Assembled Nanovehicles for Effective Cancer Therapy

Protein therapy offers promising prospects for the treatment of various important diseases, thus it is highly desirable to develop a robust carrier that can deliver active proteins into cells. The development of a novel protein delivery platform based on the self‐assembly of multiarmed amphiphilic cyclodextrins (CDEH) is reported. CDEH can self‐assemble into nanoparticles in aqueous solution and achieve superior encapsulation of protein (loading capacity > 30% w/w) simply by mixing with protein solution without introducing any subsequent cumbersome steps that may inactivate proteins. More importantly, CDEH nanovehicles can be easily further modified with various targeting groups based on host–guest complexation. Using saporin as a therapeutic protein, AS1411‐aptamer‐modified CDEH nanovehicles can preferentially accumulate in tumors and efficiently inhibit tumor growth in a MDA‐MB‐231 xenograft mouse model. Moreover, folate‐targeted CDEH nanovehicles can also deliver Cas9 protein and Plk1‐targeting sgRNA into Hela cells, leading to 47.1% gene deletion and 64.1% Plk1 protein reduction in HeLa tumor tissue, thereby effectively suppressing the tumor progression. All these results indicate the potential of targeted CDEH nanovehicles in intracellular protein delivery for improving protein therapeutics.     

Smart Supramolecular “Trojan Horse”‐Inspired Nanogels for Realizing Light‐Triggered Nuclear Drug Influx in Drug‐Resistant Cancer Cells

Efficient nuclear delivery of anticancer drugs evading drug efflux transporters (DETs) on the plasma and nuclear membranes of multidrug‐resistant cancer cells is highly challenging. Here, smart nanogels are designed via a one‐step self‐assembly of three functional components including a biocompatible copolymer, a fluorescent organosilica nanodot, and a photodegradable near‐infrared (NIR) dye indocyanine green (ICG). The rationally designed nanogels have high drug encapsulation efficiency (≈99%) for anticancer drug doxorubicin (Dox), self‐traceability for bioimaging, proper size for passive tumor targeting, prolonged blood circulation time for enhanced drug accumulation in tumor, and photocontrolled disassemblability. Moreover, the Dox‐loaded nanogels can effectively kill multidrug‐resistant cells via two steps: 1) They behave like a “Trojan horse” to escape from the DETs on the plasma membrane for efficiently transporting the anticancer “soldier” (Dox) into the cytoplasm and preventing the drugs from being excreted from the cells; 2) Upon NIR light irradiation, the photodegradation of ICG leads to the disassembly of the nanogels to release massive Dox molecules, which can evade the DETs on the nuclear membrane to exert their intranuclear efficacy in multidrug‐resistant cells. Combined with their excellent biocompatibility, the nanogels may provide an alternative solution for overcoming cancer multidrug resistance.     

Self‐Assembled Nanoparticles with Dual Effects of Passive Tumor Targeting and Cancer‐Selective Anticancer Effects

Nanoparticular drug delivery systems may help to overcome the limitations of conventional chemotherapy. They have been reported to improve the specificity of distribution, the bioavailability, and the solubility of drugs, as well as the duration of drug efficacy, and helping to overcome multidrug resistance. Although various polymeric nanoparticles have been developed for delivery of anticancer agents, most nanoparticles still focus on solubilizing drugs, improving targeting ability, and reducing side effects. In particular, targeting to the tumor is typically improved through passive or active targeting. Despite great achievements in both strategies, yet to be resolved are issues of toxicity in normal cells and enhancement of tumor‐specificity. A new approach combining the dual strategies of passive tumor targeting and cancer‐selective efficacy is proposed. Recombinant human gelatin conjugated with lipoic acid (rHG‐LA) developed in this study forms nanoparticles spontaneously in aqueous solution and encapsulates alpha‐tocopheryl succinate (α‐TOS), a well‐known cancer‐selective apoptosis‐inducing agent, within a hydrophobic core during the self‐assembly. This study describes the promising applicability of α‐TOS‐loaded rHG‐LA nanoparticles with passive targeting ability and cancer‐specificity.     

Noncovalent Polymer‐Gatekeeper in Mesoporous Silica Nanoparticles as a Targeted Drug Delivery Platform

Selective targeting of tumor cells and release of drug molecules inside the tumor microenvironment can reduce the adverse side effects of traditional chemotherapeutics because of the lower dosages required. This can be achieved by using stimuli‐responsive targeted drug delivery systems. In the present work, a robust and simple one‐pot route is developed to synthesize polymer‐gatekeeper mesoporous silica nanoparticles by noncovalent capping of the pores of drug‐loaded nanocontainers with disulfide cross‐linkable polymers. The method offers very high loading efficiency because chemical modification of the mesoporous nanoparticles is not required; thus, the large empty pore volume of pristine mesoporous silica nanoparticles is entirely available to encapsulate drug molecules. Furthermore, the polymer shell can be easily decorated with a targeting ligand for selective delivery to specific cancer cells by subsequent addition of the thiol‐containing ligand molecule. The drug molecules loaded in the nanocontainers can be released by the degradation of the polymer shell in the intracellular reducing microenvironment, which consequentially induces cell death.     

Antitumor Platelet‐Mimicking Magnetic Nanoparticles

Nanoparticles possess the potential to revolutionize cancer diagnosis and therapy. The ideal theranostic nanoplatform should own long system circulation and active cancer targeting. Additionally, it should be nontoxic and invisible to the immune system. Here, the authors fabricate an all‐in‐one nanoplatform possessed with these properties for personalized cancer theranostics. Platelet‐derived vesicles (PLT‐vesicles) along with their membrane proteins are collected from mice blood and then coated onto Fe₃O₄ magnetic nanoparticles (MNs). The resulting core–shell PLT‐MNs, which inherit the long circulation and cancer targeting capabilities from the PLT membrane shell and the magnetic and optical absorption properties from the MN core, are finally injected back into the donor mice for enhanced tumor magnetic resonance imaging (MRI) and photothermal therapy (PTT). Meanwhile, it is found that the PTT treatment impels PLT‐MNs targeting to the PTT sites (i.e., tumor sites), and exactly, in turn, the enhanced targeting of PLT‐MNs to tumor sites can improve the PTT effects. In addition, since the PLT membrane coating is obtained from the mice and finally injected into the same mice, PLT‐MNs exhibit stellar immune compatibility. The work presented here provides a new angle on the design of biomimetic nanoparticles for personalized diagnosis and therapy of various diseases.     

Doxorubicin‐Conjugated Immuno‐Nanoparticles for Intracellular Anticancer Drug Delivery

A polymeric nanoparticle comprised of surface furan groups is used to bind, by Diels–Alder (DA) coupling chemistry, both targeting anti‐human epidermal growth factor receptor 2 (anti‐HER2) antibodies and chemotherapeutic doxorubicin (DOX) for targeted, intracellular delivery of DOX. In this new approach for delivery, where both chemotherapeutic and targeting ligand are attached, for the first time, to the surface of the delivery vehicle, the nuclear localization of DOX in HER2‐overexpressing breast cancer SKBR‐3 cells is demonstrated, as determined by confocal laser scanning microscopy. Flow cytometric analysis shows that the conjugated DOX maintains its biological function and induces similar apoptotic progression in SKBR‐3 cells as free DOX. The viable cell counts of SKBR‐3 cancer cells following incubation with different nanoparticle formulations demonstrates that the combined DOX and anti‐HER2 nanoparticle is more efficacious than the nanoparticle formulation with either DOX or anti‐HER2 alone. While free DOX shows similar cytotoxicity against both cancerous SKBR‐3 cells and healthy HMEC‐1 cells, the combined DOX‐anti‐HER2 nanoparticle is significantly more cytotoxic against SKBR‐3 cells than HMEC‐1 cells, suggesting the benefit of nanoparticle‐conjugated DOX for cell type‐specific targeting. The DOX‐conjugated immuno‐nanoparticle represents an entirely new method for localized co‐delivery of chemotherapeutics and antibodies.     

Biocompatible,Uniform, and Redispersible Mesoporous Silica Nanoparticles for Cancer‐Targeted Drug Delivery In Vivo

Engineering multifunctional nanocarriers for targeted drug delivery shows promising potentials to revolutionize the cancer chemotherapy. Simple methods to optimize physicochemical characteristics and surface composition of the drug nanocarriers need to be developed in order to tackle major challenges for smooth translation of suitable nanocarriers to clinical applications. Here, rational development and utilization of multifunctional mesoporous silica nanoparticles (MSNPs) for targeting MDA‐MB‐231 xenograft model breast cancer in vivo are reported. Uniform and redispersible poly(ethylene glycol)‐incorporated MSNPs with three different sizes (48, 72, 100 nm) are synthesized. They are then functionalized with amino‐β‐cyclodextrin bridged by cleavable disulfide bonds, where amino‐β‐cyclodextrin blocks drugs inside the mesopores. The incorporation of active folate targeting ligand onto 48 nm of multifunctional MSNPs (PEG‐MSNPs48‐CD‐PEG‐FA) leads to improved and selective uptake of the nanoparticles into tumor. Targeted drug delivery capability of PEG‐MSNPs48‐CD‐PEG‐FA is demonstrated by significant inhibition of the tumor growth in mice treated with doxorubicin‐loaded nanoparticles, where doxorubicin is released triggered by intracellular acidic pH and glutathione. Doxorubicin‐loaded PEG‐MSNPs48‐CD‐PEG‐FA exhibits better in vivo therapeutic efficacy as compared with free doxorubicin and non‐targeted nanoparticles. Current study presents successful utilization of multifunctional MSNP‐based drug nanocarriers for targeted cancer therapy in vivo.     

A Versatile Prodrug Strategy to In Situ Encapsulate Drugs in MOF Nanocarriers: A Case of Cytarabine‐IR820 Prodrug Encapsulated ZIF‐8 toward Chemo‐Photothermal Therapy

Zeolitic imidazolate framework‐8 (ZIF‐8) is an attractive metal organic framework (MOF) in drug delivery. Strong interaction between drugs and ZIF‐8 is essential for high drug loadings through in situ construction of MOFs. However, only limited drugs with unique functional groups (? COOH, ? SO₃H, et al.) can interact with ZIF‐8 and be encapsulated satisfactorily so far. Drugs without these functional groups are difficult to be loaded due to the lack of strong interaction. Herein a versatile prodrug strategy is proposed to solve the problems encountered by MOFs. Cytarabine (Ara) is chosen as a model drug since it cannot be loaded in ZIF‐8 satisfactorily by itself. New indocyanine green (IR820) is utilized to bond with Ara for the formation of prodrug (Ara‐IR820) and endows the prodrug with fluorescence imaging‐guided chemo‐photothermal therapy, in which sulfonic groups strengthen the interaction between prodrug and ZIF‐8. This prodrug loaded ZIF‐8 is further functionalized with hyaluronic acid (HA) to result in active‐targeting HA/Ara‐IR820@ZIF‐8 nanoparticles. The in vitro and in vivo results demonstrate its excellent visual cancer therapy with tumor‐targeted and pH‐responsive release behavior. This design offers a new concept to solve the drug loading problem of MOFs, exhibiting a flexible strategy to expand the biomedical applications of MOFs.     

High‐Fidelity Trapping of Spatial–Temporal Mitochondria with Rational Design of Aggregation‐Induced Emission Probes

High‐fidelity trapping of mitochondrial dynamic activity is critical to value cellular functions and forecast disease but lack of spatial–temporal probes. Given that commercial mitochondria probes suffering from low photostability, aggregation‐caused quenching effect, and limited signal‐to‐noise ratio from fluorescence “always on” in the process of targeting mitochondria, here, the rational design strategy of a novel aggregation‐induced emission (AIE) molecular motif and unique insight into the high‐fidelity targeting of mitochondria is reported, thereby illustrating the relationship between tailoring molecular aggregation state and mitochondrial targeting ability. This study focuses on how to exactly modulate the hydrophilicity and the aggregated state for realizing “off‐on” fluorescence, as well as matching the charge density to go across the cell membrane for mitochondrial targeting. Probe tricyano‐methylene‐pyridine (TCM‐1) exhibits an unprecedented high‐fidelity feedback on spatial–temporal mitochondrial information with several advantages such as “off‐on” near‐infrared characteristic, high targeting capacity, favorable biocompatibility, as well as excellent photostability. TCM‐1 also produces reactive oxygen species in situ for image‐guided photodynamic anticancer therapy. Through unraveling the relationship between tuning molecular aggregation behavior and organelle‐specific targeting ability, for the first time, a unique guide is provided in designing AIE‐active probes to explore the hydrophilicity and membrane potential for targeting subcellular organelles.     

Nafion–Carbon Nanocomposite Membranes Prepared Using Hydrothermal Carbonization for Proton‐Exchange‐Membrane Fuel Cells

Nafion–carbon (NC) composite membranes were prepared by hydrothermal treatment of Nafion membrane impregnated with glucose solution. The carbon loading of the NC membrane was tuned by controlling the hydrothermal carbonization time. X‐ray diffraction, Fourier‐transform infrared spectroscopy, scanning electron microscopy, thermogravimetric analysis, and positron annihilation lifetime spectroscopy were used to characterize plain Nafion and NC composite membranes. Nafion–carbon composite membranes exhibited better proton conductivity and reduced methanol permeability than those of the plain Nafion membrane. A single cell prepared with the NC composite membrane with a carbon loading of 3.6 wt% exhibited the highest cell performance. Compared with the cell performance of plain Nafion membrane, the maximum power density of the new cell improved by 31.7% for an H₂/O₂ fuel cell at room temperature, and by 44.0% for a direct methanol fuel cell at 60 °C.     

Nano‐Self‐Assembly of Nucleic Acids Capable of Transfection without a Gene Carrier

Nonviral gene carriers based on electrostatic interaction, encapsulation, or absorption require a large amount of polymer carrier to achieve reasonable transfection efficiencies. With cationic nanoparticles, for example, genes interact only with the surface of the nanoparticles, resulting in a low surface area to volume ratio (SA/V = 3/r). A large volume of carrier, therefore, is required to deliver a small copy number of genes. In this study, it is demonstrated that a nano‐self‐assembly of nucleic acids transfects itself into cells spontaneously, without the need for a gene carrier. The cellular uptake of this nanoassembly occurs through a number of endocytosis mechanisms. Once within the cell, the nanoassembly can escape endolysosomal vesicles and facilitate gene transfection. This nano‐self‐assembly consisting of zinc and plasmid DNA or siRNA, termed the Zn/DNA or Zn/siRNA nanocluster, is formed through the binding of Zn²⁺ ions to the phosphate groups of nucleic acids. The method described in this paper represents a new platform for carrier‐free gene delivery that can be used to deliver any plasmid DNA or siRNA without the requirement for a specific modification in the nucleic acids or complicated steps to prepare dense particles.