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Carbon monoxide (CO) gas therapy combined with chemotherapy and photothermal therapy (PTT) is a promising treatment mode for malignant tumor. Herein, we firstly reported doxorubicin (DOX) loaded Mn carbonyl modified Fe (Ⅲ)-based nanoMOFs (MIL-100) coated PEGylated magnetic carbon nanoparticles (denoted as MCM@PEG-CO-DOX NPs) as theranostics nanoplatforms for near-infrared (NIR)-responded CO-DOX combination therapy. MIL-100 as a good nanocarrier of DOX with high loading capacity can also chelate the Mn carbonyl after a smart modification. Meanwhile, magnetic carbon core possessed photothermal effect, which can convert the NIR light to heat by an 808 nm laser irradiation, resulting in the on-demand release of CO and DOX. As a result, combining with PTT, MCM@PEG-CO-DOX NPs killed tumor efficiently. Moreover, our synthesized MCM@PEG-CO-DOX NPs were capable of realizing tumor dual-mode imaging including magnetic resonance imaging (MRI) and photoacoustic imaging (PAI)., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The pursuit of multifunctional, innovative, more efficient, and safer cancer treatment has gained increasing interest in the research of preclinical nanoparticle-mediated photothermal therapy (PTT). Cell nucleus is recognized as the ideal target for cancer treatment because it plays a central role in genetic information and the transcription machinery reside. In this work, an efficient nuclear-targeted PTT strategy is proposed using transferrin and TAT peptide (TAT: YGRKKRRQRRR) conjugated monodisperse magnetic nanoparticles, which can be readily functionalized and stabilized for potential diagnostic and therapeutic applications. The monodisperse magnetic nanoparticles exhibit high photothermal conversion efficiency (≈37%) and considerable photothermal stability. They also show a high magnetization value and transverse relaxivity (207.1 mm -1 s -1 ), which could be applied for magnetic resonance imaging. The monodisperse magnetic nanoparticles conjugated with TAT peptides can efficiently target the nucleus and achieve the imaging-guided function, efficient cancer cells killing ability. Therefore, this work may present a practicable strategy to develop subcellular organelle targeted PTT agents for simultaneous cancer targeting, imaging, and therapy., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The development of theranostic systems capable of diagnosis, therapy, and target specificity is considerably significant for accomplishing personalized medicine. Here, a multifunctional rattle-type nanoparticle (MRTN) as an effective biological bimodal imaging and tumor-targeting delivery system is fabricated, and an enhanced loading ability of hydrophobic anticancer drug (paclitaxel) is also realized. The rattle structure with hydrophobic Fe3 O4 as the inner core and mesoporous silica as the shell is obtained by one-step templates removal process, and the size of interstitial hollow space can be easily adjusted. The Fe3 O4 core with hydrophobic poly(tert-butyl acrylate) (PTBA) chains on the surface is not only used as a magnetic resonance imaging (MRI) agent, but contributes to improving hydrophobic drug loading amount. Transferrin (Tf) and a near-infrared fluorescent dye (Cy 7) are successfully modified on the surface of the nanorattle to increase the ability of near-infrared fluorescence (NIRF) imaging and tumor-targeting specificity. In vivo studies show the selective accumulation of MRTN in tumor tissues by Tf-receptor-mediated endocytosis. More importantly, paclitaxel-loaded MRTN shows sustained release character and higher cytotoxicity than the free paclitaxel. This theranostic nanoparticle as an effective MRI/NIRF bimodal imaging probe and drug delivery system shows great potential in cancer diagnosis and therapy., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A strategy to prepare doxorubicin-loaded magnetic silk fibroin nanoparticles is presented. The nanoparticles serve as a nanometer-scale drug-delivery system in the chemotherapy of multidrug-resistant cancer under the guidance of a magnetic field. The magnetic tumor-targeting ability broadens the range of biomedical applications of silk fibroin, and the nanoparticle-assisted preparation strategy is useful for the advancement of other biomacromolecule-based materials., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The objective of this study was to develop and evaluate the antitumor activity and the safety of a delivery system containing mesoporous silica nanoparticles (MSN) coated with pH-responsive poly (N-isopropylacrylamide-co-methacrylic acid; P NIPAM-co-MAA) for doxorubicin (DOX) delivery (P-MSN-DOX) in vitro and in vivo. We reported that P-MSN-DOX nanoparticles (190 ± 30 nm) offered a DOX-loading coefficient of more than 20%. DOX release from the P-MSN-DOX formulation was pH-dependent with enhanced antitumor effects in vitro compared with traditional MSN-DOX, which was weakly cytotoxic due to negligible drug release at tested pHs. P-MSN-DOX circulated longer, with less cardiac and renal accumulation as shown by pharmacokinetics and biodistribution studies in vivo. Also, the P-MSN-DOX delivery system had greater antitumor activity in mice bearing a murine sarcoma S-180 cell line. This finding was correlated with both in vitro and in vivo. Subacute toxicity tests revealed a low P-MSN-DOX toxicity in vivo, as well. Thus, P-MSN-DOX appears to be an efficacious and safe cancer treatment strategy., (Copyright © 2013 Elsevier B.V. All rights reserved.)

pH-responsive composite microspheres, consisting of a core of Fe₃O₄ nanoparticle, a sandwiched layer of mesoporous silica and a shell of crosslinked poly (methacrylic acid) (PMAA), were successfully synthesized via distillation precipitation polymerization. The pKa of the composite microsphere increased with the increase in the crosslinking density. Doxorubicin hydrochloride (DOX) was applied as a model drug, and the behavior of drug storage/release was investigated. The cumulative release of DOX-loaded composite microsphere in vitro showed that the drug release rate was much faster below its pKa than that of above its pKa. Because pH of most tumor tissues was lower than that of normal tissues, the pH-responsive composite microspheres are promising drug delivery system especially for cancer therapy., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The ammonium glycyrrhizinate-loaded chitosan nanoparticles were prepared by ionic gelation of chitosan with tripolyphosphate anions (TPP). The particle size and zeta potential of nanoparticles were determined, respectively, by dynamic light scattering (DLS) and a zeta potential analyzer. The effects, including chitosan molecular weight, chitosan concentration, ammonium glycyrrhizinate concentration and polyethylene glycol (PEG) on the physicochemical properties of the nanoparticles were studied. These nanoparticles have ammonium glycyrrhizinate loading efficiency. The encapsulation efficiency decreased with the increase of ammonium glycyrrhizinate concentration and chitosan concentration. The introduction of PEG can decrease significantly the positive charge of particle surface. These studies showed that chitosan can complex TPP to form stable cationic nanoparticles for subsequent ammonium glycyrrhizinate loading.

In this study, we reported a strategy to improve delivery efficiency of a long-circulation biomimetic photothermal nanoagent for enhanced photothermal therapy through selectively dilating tumor vasculature. By using a simply nanocoating technology, a biomimetic layer of natural red blood cell (RBC) membranes was camouflaged on the surface of photothermal polypyrrole nanoparticles (PPy@RBC NPs). The erythrocyte-mimicking PPy NPs inherited the immune evasion ability from natural RBC resulting in superior prolonged blood retention time. Additionally, excellent photothermal and photoacoustic imaging functionalities were all retained attributing to PPy NPs cores. To further improve the photothermal outcome, the endothelin A (ET A ) receptor antagonist BQ123 was jointly employed to regulate tumor microenvironment. The BQ123 could induce tumor vascular relaxation and increase blood flow perfusion through modulating an ET-1/ET A transduction pathway and blocking the ET A receptor, whereas the vessel perfusion of normal tissues was not altered. Through our well-designed tactic, the concentration of biomimetic PPy NPs in tumor site was significantly improved when administered systematically. The study documented that the antitumor efficiency of biomimetic PPy NPs combined with specific antagonist BQ123 was particularly prominent and was superior to biomimetic PPy NPs ( P < 0.05) and PEGylated PPy NPs with BQ123 ( P < 0.01), showing that the greatly enhanced photothermal treatment could be achieved with low-dose administration of photothermal agents. Our findings would provide a promising procedure for other similar enhanced photothermal treatment by blocking ET A receptor to dramatically increase the delivery of biomimetic photothermal nanomaterials. [ABSTRACT FROM AUTHOR]

Highlights: [•] Monodisperse core–shell nanocomposites with fluorescent solid SiO2 core mesoporous silica shell. [•] DOX release study for F-nSiO2/mSiO2 with different shell thickness as carrier. [•] Smaller nanoparticles will be uptaken by HeLa cells easier. [ABSTRACT FROM AUTHOR]

Abstract: pH-sensitive poly(l-glutamic acid) grafted mesoporous silica nanoparticles (MSN-PLGA) were prepared by the surface-initiated N-carboxyanhydride polymerization method. The resultant MSN-PLGA was well dispersed in aqueous medium and showed high drug loading efficiency, superior stability, and significantly higher drug release rates. The cumulative release of doxorubicin hydrochloride (DOX) from DOX-loaded MSN-PLGA (DOX@MSN-PLGA) was pH-dependent and the release rate was much higher at pH 5.5 than that at pH 7.4. The cytotoxicity results indicated that the blank MSN-PLGA was biocompatible and the DOX@MSN-PLGA had potent in vitro cytotoxicity effect similar to free DOX. Overall, these results demonstrate that MSN-PLGA is a promising platform to build pH controlled drug delivery systems for cancer therapy. [Copyright &y& Elsevier]

Abstract: Mesoporous silica-encapsulated gold nanorods (GNRs@mSiO2) have great potential both in photothermal therapy and drug delivery. In this paper, we firstly developed GNRs@mSiO2 as a synergistic therapy tool for delivery heat and drug to the tumorigenic region. We studied the ablation of tumor both in vitro and in vivo by the combination of photothermal therapy and chemotherapy using doxorubicin (DOX)-loaded GNRs@mSiO2. Significantly greater cell killing was observed when A549 cells incubated with DOX-loaded GNRs@mSiO2 were irradiated with near-infrared (NIR) illumination, attributable to both GNRs@mSiO2-mediated photothermal ablation and cytotoxicity of light-triggered DOX release. We then performed in vivo therapy studies and observed a promising tumor treatment. Compared with chemotherapy or photothermal treatment alone, the combined treatment showed a synergistic effect, resulting in higher therapeutic efficacy. Furthermore, the lower systematic toxicity of GNRs@mSiO2 has been validated. [Copyright &y& Elsevier]

The design of bioresponsive controlled drug delivery systems isa promising approach in cancer therapy, but it still is a major challengecapable of optimum therapeutic efficacy, i.e. no premature drug leakagein blood circulation while having a rapid and complete release intumor tissues. In this work, a kind of PEGylated core/shell structuredcomposite nanoparticle was developed via precipitation polymerization,where a disulfide-cross-linked poly(N-vinylcaprolactam-co-methacrylic acid) (P(VCL-s-s-MAA)) polymer shell was created to act as sheddable thermo/pH-sensitivegatekeepers, and a carboxylic acid modified mesoporous silica nanoparticles(MSN-COOH) core was applicable as an accessible reservoir to encapsulatehigh drug doses. At physiological conditions, the P(VCL-s-s-MAA)-PEG shell underwent a distinct transitionfrom a swollen state in pH 7.4 to a collapsed state in pH 5.0. Thoughsufficiently stable in water, composite nanoparticles were prone tofast dissociation and rupture when subjecting to 10 mM glutathione(GSH), due to the shedding of polymer walls through reductive cleavageof intermediate disulfide bonds, so that the polymer shell was activein moderating the diffusion of embedded drugs in-and-out of MSN channels.The cumulative in vitrorelease of DOX-loaded compositenanoparticles allowed a low trace of DOX diffusion below volume phasetransition temperature (VPTT) and a significant release rate aboveits VPTT, while the most rapid and perfect release was achieved undera reductive environment (pH 6.5 and 10 mM GSH), mimicking that ofintracellular cytosol compartments. The in vitrocellassay of blank carriers to normal cells indicated that the compositenanoparticles were suitable as drug carriers, but DOX-loaded carriershad a similar intensive toxicity to cancer cells compared with freeDOX. Therefore, these stimuli-responsive composite nanoparticles witha reductively sheddable and thermo/pH-responsive polymer shell gatecould, in principle, be applied for in vivocancertherapy, and synergistic drug delivery can be accomplished “justin time” in a precise event over the location. [ABSTRACT FROM AUTHOR]

Abstract: In this study, hyperbranched polyamidoamine (hPAMAM) was developed as a novel non-viral gene vector for the first time. The hPAMAM was synthesized using a modified “one-pot” method. DNA was then bound to hPAMAM at different weight ratios (whPAMAM/wDNA). The higher weight ratio could bring larger particle size and higher zeta potential of hPAMAM–DNA complexes. The encapsulated DNA was protected by hPAMAM from degradation for over 3h. Under the optimal condition, high gene transfection efficiency could be achieved in COS7 (47.47±1.42%) and HEK293 (40.8±0.98%) cell lines. And hPAMAM showed rather minor cytotoxicity in vitro (cell viability=91.38±0.46% in COS7 and 92.38±0.61% in HEK293). The hPAMAM mediated human vascular endothelial growth factor 165 (hVEGF165) gene transfected cells could express hVEGF165 stably for 14 days, with the peak expression at day 2. In conclusion, hPAMAM based gene delivery was economical, effective and biocompatible, and may serve as a promising non-viral vehicle for gene therapy. [Copyright &y& Elsevier]

Abstract: pH-responsive polymer shell chitosan/poly (methacrylic acid) (CS-PMAA) was coated on mesoporous silica nanoparticles (MSN) through the facile in situ polymerization method. The resultant composite microspheres showed a flexible control over shell thickness, surface charges and hydrodynamic size by adjusting the feeding amount of MSN and the molar ratio of [–NH2]/MAA. The MSN/CS-PMAA composite microspheres were stable in the pH range of 5–8 as well as in the physiological saline (0.15M NaCl). Doxorubicin hydrochloride (DOX) was applied as a model drug to investigate the drug storage and release behavior. The results demonstrated that DOX could be effectively loaded into the composite microspheres. The cumulative release of DOX-loaded composite microspheres was pH dependent and the release rate was much faster at low pH (5.5) than that of pH 7.4. The cytotoxicity test by MTT assay showed that the blank carrier MSN/CS-PMAA microspheres were suitable as drug carriers. The cellular uptake of composite microspheres was investigated by confocal laser scanning microscopy (CLSM), which indicated that MSN/CS-PMAA could deliver the drugs into HeLa cell. The above results imply that the composite microspheres are a promising drug delivery system for cancer therapy. [Copyright &y& Elsevier]

Long blood circulation is the basic requirement of advanced drug delivery systems for tumor treatment, which leads to enhanced tumor therapeutic efficiency and reduced side effects. However, the pharmacokinetics of the current nanoparticles in vivo is still unsatisfactory, which leads to limited success to translate nanoparticles into clinical applications. Inspired by the natural cell membrane-coating strategy, a series of zwitterionic polymer membranes are firstly developed and coated onto different kinds of nanoparticles in this work. Intriguingly, the zwitterionic polymer membrane shows stronger protein adsorption resistance and reduced macrophage uptake compared with the corresponding zwitterionic polymer brush or the red blood cell (RBC) membrane, which results in longer blood circulation time and higher tumor accumulation of the coated nanoparticles. Combined with the photothermal effect of model nanoparticles, Fe 3 O 4 , zwitterionic polymer membrane-coated Fe 3 O 4 shows enhanced photothermal therapy (PTT) efficacy on A549 tumors compared with the corresponding zwitterionic polymer brush or RBC membrane-coated Fe 3 O 4. Notably, Fe 3 O 4 coated by carboxybetaine-based biomimic membranes exhibits the ultra-long blood circulation (t 1/2 = 96.0 h) and strongest PTT efficacy compared with those coated by phosphorylcholine-based or sulfobetaine-based biomimic membranes. In addition, the zwitterionic biomimic membrane exhibits rapid glutathione-triggered degradation with the products of low molecular weight (<2000 g mol−1). Therefore, the biodegradable zwitterionic biomimic membrane coating offers a universal platform for the design and application of long-circulating biomedical nanoparticles, which may pave the way for the clinical applications of biomedical nanoparticles in tumor therapy. [ABSTRACT FROM AUTHOR]