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Conventional chemotherapy is bothered by systematic toxicity and confined therapeutic effects. Gas therapy has emerged as a potent tumor treatment, and hydrogen sulfide (H2S), a traditional gasotransmitter, has been found to show a tumor inhibition effect. Therefore, we established a mesoporous organosilica-based H2S nanogenerator (MON-TPGS-DOX). Tetrasulfide bond-incorporated mesoporous organosilica nanoparticles were modified with d-α-tocopheryl polyethylene glycol succinate (TPGS), namely, MON-TPGS, and then loaded with doxorubicin (DOX) to obtain the nanogenerator. Tetrasulfide bonds in the nanogenerator could be triggered by glutathione (GSH) to release H2S, further resulting in the degradation of nanogenerator and DOX release. GSH consumption and H2S release led to oxidative stress in 4T1 cells, activation of apoptotic signaling cascades, and enhanced cell-killing effect. Furthermore, the nanogenerator effectively suppressed tumor growth in a tumor-bearing mice model with good biosafety, providing a promising approach for H2S-enhanced tumor chemotherapy. [ABSTRACT FROM AUTHOR]

Photothermal therapy (PTT) in the second near-infrared window (NIR-II, 1000-1350 nm) has presented great superiority in cancer treatment recently. However, it is generally limited to a few photothermal agents and most of them often suffer from intricate design and complicated synthesis. Herein, by subtly extracting nanoparticles from ancient ink (AINPs), a versatile AINP dispersion with definite ingredients, good biosafety, and excellent photothermal effect in the NIR-II window was obtained. In vivo trials demonstrated that the obtained AINP dispersion provides a promising alternative for tumor sentinel lymph node (SLN) mapping. Besides, under the guidance of photoacoustic imaging, the metastatic SLNs could be accurately eliminated by NIR-II laser irradiation. The preliminary biosafety of AINP dispersion has also been systematically confirmed. Therefore, we believe this work would provide a green and effective strategy for PTT of tumor in the NIR-II window., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Combination of photothermal therapy (PTT) and photodynamic therapy (PDT) has become a promising cancer treatment in recent years. However, their applications are limited by complex synthetic protocols and low efficacy. Hence, optimizing experimental approach and improving the efficiency of phototherapy is the current research focus. In this work, various pyrolysis temperatures and sizes of zeolitic imidazolate framework-8 (ZIF-8) derived carbon nanoparticles (ZCNs) are obtained by a simple direct pyrolysis of the ZIF-8 nanoparticles. Meanwhile, the ZCNs can be used as photothermal agents and photosensitizers to produce heat and reactive oxygen species simultaneously upon near-infrared laser irradiation. Moreover, it is observed that the phototherapy effects and photoacoustic (PA) signal of ZCNs could be enhanced with the increase in the nanoparticle size. Subsequently, guided by PA imaging, the therapeutic effect of ZCNs is investigated on a small animal model, where tumors are entirely eliminated with minimal side effect, demonstrating the high efficacy of the larger size of ZCNs through combination of PTT and PDT. Therefore, it is expected that the ZCN is a simple and highly effective phototherapeutic platform for oncotherapy, and the concept of size-dependent enhanced behavior of phototherapy and PA imaging will be very useful in the development of nanomaterials for cancer therapy.

Autophagy is a conservative eukaryotic pathway which plays a crucial role in maintaining cellular homeostasis, and dysfunction of autophagy is usually associated with pathological conditions. Recently, emerging reports have stressed that various types of nanomaterials and therapeutic approaches interfere with cellular autophagy process, which has brought up concerns to their future biomedical applications. Here, we present a study elaborating the relationships between autophagy and iron oxide nanoparticle (IONP)-mediated photothermal therapy in cancer treatment. Our results reveal that IONP photothermal effect could lead to autophagy induction in cancerous MCF-7 cells in a laser dose-dependent manner, and the inhibition of autophagy would enhance the photothermal cell killing by increasing cell apoptosis. In an MCF-7 xenograft model, cotreatment of autophagy inhibitor and IONP under laser exposure could promote the tumor inhibition rate from 43.26 to 68.56%, and the tumor immunohistochemistry assay of microtubule-associated protein 1-light chain 3 (LC3) and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling also demonstrate augmentation in both autophagosomes accumulation and apoptosis in vivo. This work helps us to better understand the regulation of autophagy during IONP-mediated photothermal therapy and provides us with a potential combination therapeutic approach of autophagy modulators and photothermal agents.

Zwitterionic nanocarriers have emerged as a new class of biocompatible nanomaterials with outstanding stealth capability in blood circulation. In this work, a novel biodegradable zwitterionic nanogel based on poly(sulfobetaine methacrylate) (PSBMA) was developed for reduction-responsive drug delivery to tumors. PSBMA nanogels were facilely fabricated by one-step reflux precipitation polymerization with the advantage of being surfactant-free and time-saving. The disulfide bond not only endowed the nanogels degradability in a reduction environment but also be modified with a fluorescent group after partial reduction. In vitro release experiments disclosed that doxorubicin (DOX)-loaded PSBMA nanogels could hold the drugs firmly in physiological conditions (only 7% release in 24 h) and release the drugs rapidly and sufficiently in 10 mM glutathione (85% in 8 h). More interestingly, PSBMA nanogels displayed long circulation in blood after intravenous injection, and small change was found in half-life of nanogels between the first (34.1 h) and the second injection (30.5 h), indicating that there was no accelerated blood clearance phenomenon for these nanogels. Meanwhile, no obvious immunogenic response was detected after PSBMA nanogels were injected into BALB/c mice. Furthermore, PSBMA nanogels showed a high accumulation of 9.5 and 10.7% of injected dose per gram of tissue in tumors at 24 and 48 h post intravenous injection, respectively. With outstanding long circulation time, high tumor accumulation, and sufficient drug release in a reduction environment, DOX-loaded PSBMA nanogels demonstrated the strongest tumor growth inhibition effect among all of the treatment groups in human hypopharyngeal carcinoma-bearing mouse models. Therefore, our study provided a facile drug delivery platform based on biodegradable zwitterionic nanogels and may have great potential in tumor drug delivery.

Nowadays, fluorescence detection has emerged as one of the most frequently used noninvasive biosensing methods to selectively monitor biological processes within living systems. Among fluorescent nanoparticles (NPs), gold nanoclusters (AuNCs) have been intensively studied because of their intrinsic fluorescence and their endowed biocompatible surface. Herein, we selected an abundant, low-cost, and sustainable plant protein, the pea protein isolate (PPI), for its excellent biocompatibility, biodegradability, and nonallergenic character to be employed as both a reducing and stabilizing agent to facilely produce AuNCs exhibiting a strong red fluorescence. Afterward, the formed AuNCs/PPI mixture was able to self-assemble into NPs (AuNCs/PPI NPs) with the size of about 100 nm simply through a dialyzing process. Taking advantage from the protein nature of PPI, AuNCs/PPI NPs demonstrate both excellent biocompatibility and colloidal stability. Moreover, AuNCs/PPI NPs showed a great capability when employed as a bioimaging probe for both in vitro and in vivo imaging. Finally, AuNCs/PPI NPs were coated with red blood cell (RBC) membranes to improve their blood circulation property and enhance their tumor enrichment ability to meet the requirement for practical use. Results convincingly show that such super NPs (RBC-coated AuNCs/PPI NPs) were able to successfully locate tumor in vivowith an excellent imaging capability, which provides a new strategy for bioimaging with fluorescent NPs.

Finding a simple and effective strategy to eliminate tumor metastatic lymph nodes is highly desired in clinical tumor treatment. Herein, we reported a Chinese traditional ink (Hu-ink)-based treatment for photothermal therapy (PTT) of tumor metastatic lymph nodes. By simple dilution, stable Chinese traditional ink dispersion was obtained, which presents excellent photothermal effect because of its high absorption in near-infrared (NIR) region. Meanwhile, as revealed by staining and photoacoustic imaging, Hu-ink could transfer to nearby lymph nodes after directly injected into the primary tumors. Under the guidance of dual-modality mapping, the metastatic sentinel lymph nodes could be subsequently eliminated by NIR irradiation. The good biocompatibility of Hu-ink has also been verified by a series of experiments. Therefore, the Hu-ink-based treatment exhibits great potential for PTT of tumor metastatic lymph nodes in future clinical practice., Competing Interests: The authors declare no competing financial interest.

Recently, photothermal therapy (PTT) that utilizes photothermal conversion (PTC) agents to ablate cancer under near-infrared (NIR) irradiation has attracted a growing amount of attention because of its excellent therapeutic efficacy and improved target selectivity. Therefore, exploring novel PTC agents with an outstanding photothermal effect is a current research focus. Herein, we reported a polydopamine-coated magnetic composite particle with an enhanced PTC effect, which was synthesized simply through coating polydopamine (PDA) on the surface of magnetic Fe3O4 particles. Compared with magnetic Fe3O4 particles and PDA nanospheres, the core-shell nanomaterials exhibited an increased NIR absorption, and thus, an enhanced photothermal effect was obtained. We demonstrated the in vitro and in vivo effects of the photothermal therapy using our composite particles and their ability as a contrast agent in the T2-weighted magnetic resonance imaging. These results indicated that the multifunctional composite particles with enhanced photothermal effect are superior to magnetic Fe3O4 particles and PDA nanospheres alone.

While much effort has been made to prepare magnetic microspheres (MMs) with surface moieties that bind to affinity tags or fusion partners of interest in the recombinant proteins, it remains a challenge to develop a generic platform that is capable of incorporating a variety of capture ligands by a simple chemistry. Herein, we developed core-shell structured magnetic microspheres with a high magnetic susceptibility and a low nonspecific protein adsorption. Surface functionalization of these MMs with azide groups facilitates covalent attachment of alkynylated ligands on their surfaces by "click" chemistry and creates a versatile platform for selective purification and immobilization of recombinant proteins carrying corresponding affinity tags. The general applicability of the approach was demonstrated in incorporating four widely used affinity ligands with different reactive groups (-CHO, -SH, -COOH, and -NH2) onto the MMs platform for purification and immobilization of targeted proteins. The azide-functionalized MMs would be applicable for a variety of ligands and substrates that are amenable to alkynylation modification.

Fluorescent carbonaceous nanodots (CDs) have attracted much attention due to their unique properties. However, their application in noninvasive imaging of diseased tissues was restricted by the short excitation/emission wavelengths and the low diseased tissue accumulation efficiency. In this study, CDs were prepared from glucose and glutamic acid with a particle size of 4 nm. Obvious emission could be observed at 600 to 700 nm when CDs were excited at around 500 nm. This property enabled CDs with capacity for deep tissue imaging with low background adsorption. Angiopep-2, a ligand which could target glioma cells, was anchored onto CDs after PEGylation. The product, An-PEG-CDs, could target C6 glioma cells with higher intensity than PEGylated CDs (PEG-CDs), and endosomes were involved in the uptake process. In vivo, An-PEG-CDs could accumulate in the glioma site at higher intensity, as the glioma/normal brain ratio for An-PEG-CDs was 1.73. The targeting effect of An-PEG-CDs was further demonstrated by receptor staining, which showed An-PEG-CDs colocalized well with the receptors expressed in glioma. In conclusion, An-PEG-CDs could be successfully used for noninvasive glioma imaging.

In this work, maltodextrin-modified magnetic microspheres Fe3O4@SiO2-Maltodextrin (Fe3O4@SiO2-MD) with uniform size and fine morphology were synthesized through a facile and low-cost method. As the maltodextrins on the surface of microspheres were combined with maltose binding proteins (MBP), the magnetic microspheres could be applied to enriching standard MBP fused proteins. Then, the application of Fe3O4@SiO2-MD in one-step purification and immobilization of MBP fused proteins was demonstrated. For the model protein we examined, Fe3O4@SiO2-MD showed excellent binding selectivity and capacity against other Escherichia coli proteins in the crude cell lysate. Additionally, the maltodextrin-modified magnetic microspheres can be recycled for several times without significant loss of binding capacity.

In this work, core-shell-shell-structured boronic acid-functionalized magnetic composite microspheres Fe3O4@SiO2@poly (methyl methacrylate-co-4-vinylphenylbornoic acid) (Fe3O4@SiO2@P(MMA-co-VPBA)) with a uniform size and fine morphology were synthesized. Here, Fe3O4 magnetic particles were prepared by a solvothermal reaction, whereas the Fe3O4@SiO2 microspheres with a core-shell structure were obtained by a sol-gel process. 3-(Trimethoxysilyl) propyl methacrylate (MPS)-modified Fe3O4@SiO2 was used as the seed in the emulsion polymerization of MMA and VPBA to form the core-shell-shell-structured magnetic composite microspheres. As the boronic acid groups on the surface of Fe3O4@SiO2@P(MMA-co-VPBA) could form tight yet reversible covalent bonds with the cis-1,2-diols groups of glycoproteins, the magnetic composite microspheres were applied to enrich a standard glycoprotein, horseradish peroxidase (HRP), and the results demonstrated that the composite microspheres have a higher affinity for the glycoproteins in the presence of the nonglycoprotein bovine serum albumin (BSA) over HRP. Additionally, different monomer mole ratios of MMA/VPBA were studied, and the results implied that using MMA as the major monomer could reduce the amount of VPBA with a similar glycoprotein enrichment efficiency but a lower cost.

Poly(vinylcaprolactam) (PVCL)-based biodegradable microgels were prepared for the biomedical application as drug delivery system via precipitation polymerization, where N,N-bis(acryloyl) cystamine (BAC) served as cross-linker, methacrylic acid (MAA) and polyethylene glycol (PEG) methyl ether methacrylate acted as comonomers. The microgels with excellent stability had distinct temperature sensitivity as largely observed in the case of PVCL-based particles and their volume phase transition temperature (VPTT) shifted to higher temperature with increasing MAA content and ambient pH. In the presence of reducing agent glutathione (GSH) or dithiothreitol (DTT), the microgels could be degraded into individual linear polymer chains by the cleavage of the disulfide linkages coming from the cross-linker BAC. The microgels could effectively encapsulate Doxorubicin (DOX) inside and presented stimuli-triggered drug release in acidic or reducing environment. The results of the cytotoxicity assays further demonstrated that the blank microgels were nontoxic to normal cells while DOX-loaded microgels presented efficient antitumor activity to HeLa cells.

The synthesis of functionalized magnetic polymer microspheres was described by a process involving (1) preparation of the monodisperse magnetic seeds according to a two-step procedure including the preparation of bilayer-oleic acid-coated Fe3O4 nanoparticles followed by soap-free emulsion polymerization with methyl methacrylate (MMA) and divinyl benzene (a cross-linking agent, DVB); (2) seeded emulsion polymerization proceeding under the continuous addition of glycidyl methacrylate (GMA) monomers in the presence of the magnetic PMMA seeds; and (3) chemical modification of the PGMA shells with ethylenediamine (EDA) to yield amino groups. As such, the magnetic poly(MMA-DVB-GMA) microspheres were prepared possessing monodispersity, uniform magnetic properties, and abundant surface amino groups. Then, the dendritic poly(amidoamine) (PAMAM) shells were coated on the magnetic particles on the basis of the Michael addition of methyl acrylate and the amidation of the resulting ester with a large excess of EDA, which could achieve generational growth under such uniform stepwise reactions. For improving the luminescence properties of the composite particles, fluorescein isothiocyanate, which is a popular organic dye, was reacted with the terminal -NH2 groups from the dendritic PAMAM shells, resulting in the formation of multifunctional microspheres with excellent photoluminescence, superparamagnetic, and pH-sensitive properties. In this case, it can be expected that an extension of the functionalization of these microspheres is to immobilize other target molecules onto the PAMAM shells to introduce other desired functions for potential chemical and biological applications.

Magnetite nanoparticles of Fe(3)O(4) have been found to grow into large highly branched nanostructures including nanochains and highly branched nanotrees in the solid state through a postannealing process. By varying the preparation conditions such as annealing time and temperature, the nanostructures could be easily manipulated. Changing the starting concentration of the magnetic nanoparticle solution also caused significant changes of the nanoarchitectures. When the magnetic nanoparticle concentration is low, the nanoparticles formed straight rods mainly with an average diameter of 80 nm and a length of several microns. With increasing concentration of the nanoparticles, treelike structures began to form. With further increase of the concentration, well-ordered nanostructures with the appearance of snowflakes were generated. The driving force for the formation of the highly ordered nanostructures includes interaction between the nanoparticles and interaction through surface-capping molecules. This experiment demonstrates that novel nanostructures can be generated by self-assembly of magnetic nanoparticles under the solid state.

A modified method to prepare high-quality thiol-capped CdTe nanocrystals (NCs) was reported in this paper. The experimental results showed that the different molar ratios of the ligands (thioglycolic acid) to monomers (Cd2+ ions) in the precursor solution played an important role in the photoluminescence (PL) quantum yield (QY) of the as-prepared CdTe NCs. When [ligand]/[monomer] = 1.2, the maximum fluorescent emission peak appeared in the orange-red window, and the PL QY increased up to 50% at room temperature without any postpreparative treatment. In the meantime, suitable reaction conditions were in favor of the optimization of the surface structure of NCs, resulting in the relatively high PL QY from green to red. In addition, some differences between hydrothermal synthesis and traditional aqueous synthesis of CdTe NCs were discussed.