Search

Abstract: 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±30nm) 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 &y& Elsevier]

A controlled drug-delivery system has been developed based on mesoporous silica nanoparticles that deliver anticancer drugs into cancer cells with minimized side effects. The copolymer of two oligo(ethylene glycol) macromonomers cross-linked by the disulfide linker N, N′-bis(acryloyl)cystamine is used to cap hollow mesoporous silica nanoparticles (HMSNs) to form a core/shell structure. The HMSN core is applied as a drug storage unit for its high drug loading capability, whereas the polymer shell is employed as a switch owing to its redox/temperature dual responses. The release behavior in vitro of doxorubicin demonstrated that the loaded drugs could be released rapidly at higher temperature or in the presence of glutathione (GSH). Thus, the dual-stimulus polymer shell exhibiting a volume phase transition temperature higher than 37 °C can effectively avoid drug leakage in the bloodstream owing to the swollen state of the shell. Once internalized into cells, the carriers shed the polymer shell because of cleavage of the disulfide bonds by GSH, which results in the release of the loaded drugs in cytosol. This work may prove to be a significant development in on-demand drug release systems for cancer therapy. [ABSTRACT FROM AUTHOR]

Abstract A multifunctional CO/thermo/chemotherapy nanoplatform is here reported, which is composed of mesoporous carbon nanoparticles (MCN) as near infrared (NIR)-responsive drug carrier, doxorubicin (DOX) as chemotherapeutic drug and triiron dodecacarbonyl (FeCO) as thermosensitive CO prodrug. The nanoplatform could absorb near-infrared (NIR) light and convert it into ample heat to trigger CO release and could also release DOX in the acidic tumor microenvironment. More importantly, the generated CO molecules successfully increase cancer cell sensitivity to chemotherapeutics by the ferroptosis pathway. Subsequently, under the guidance of photoacoustic imaging, the FeCO-DOX@MCN nanoplatform demonstrates high treatment efficacies in vitro and in vivo by combination of chemotherapy, photothermal therapy and gas therapy. This multifunctional platform with excellent antitumor efficacy has great potential in precision cancer therapy. [ABSTRACT FROM AUTHOR]

Multifunctional nanoparticles for selectively targeting tumor cells and effectively delivering multiple drugs are urgently needed in cancer therapy. Here, a dual-drug delivery system is prepared, based on functionalized hollow mesoporous silica nanoparticles (HMSNs). Doxorubicin (DOX) hydrochloride is loaded into the hollow core, and dichloro(1,2-diaminocyclohexane)platinum (II) (DACHPt) is stored in the pores of the shell by the coordination interaction with the carboxyl groups modified on the pore walls, which also serves as barriers to control the DOX release. Detailed studies in vitro indicate that the DACHPt release is triggered by Cl− through the cleavage of the coordination interaction, and the DOX release depends on the release rate of DACHPt and the environmental pH value. The surface of the mechanized nanoparticles is also modified by transferrin (Tf) to achieve the tumor specificity. Compared with individual drug delivery systems, the dual-drug delivery system shows synergistic efficacy on the cell cytotoxicity (combination index = 0.30), resulting in improved tumor cell killing. The present dual-drug delivery system provides a promising strategy to develop controlled and targeted combination therapies for efficient cancer treatment. [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: 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 &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: A general and facile strategy was developed to coat hydrophilic inorganic nanoparticles directly with mesoporous silica nanoparticles (MSNs). The cationic surfactant of cetyltrimethylammonium bromide (CTAB) was adsorbed to various negatively charged CdTe quantum dots, Fe3O4 nanocrystals or Au nanoparticles, introducing the bilayer of CTAB overcoating with positive charge. The subsequent sol–gel reaction of TEOS with the basic catalyst resulted in uniform nanocomposites. The concentration of CTAB and NH4OH in the recipe strongly influenced the number of inorganic nanoparticles in the nanocomposites and the homogeneity of MSNs shell. One dimensional Au nanorods and larger size of solid SiO2 nanoparticles were also able to coat with MSNs using a similar synthetic procedure. The proposed method was greatly simplified without the help of any mediators or silane coupling agents and excellent mesostructural performance was readily achieved. Compared to the methods known from the literatures for the coating of hydrophobic nanoparticles, this efficient way is especially useful for trapping different hydrophilic nanoparticles with arbitrary sizes and shapes into MSNs. These highly versatile multifunctional nanocomposites, together with the pH-responsible drug release behaviors, non-toxicity to normal cells and ease of uptake into cancer cells, are expected to be utilized as drug delivery system for simultaneous imaging and therapeutic applications. [Copyright &y& Elsevier]