Multifunctional Mesoporous Silica Nanoparticles Research Articles

Boron-Containing Mesoporous Silica Nanoparticles with Effective Delivery and Targeting of Liver Cancer Cells for Boron Neutron Capture Therapy.

Nanocarriers have been researched comprehensively for the development of novel boron-containing agents in boron neutron capture therapy (BNCT). We designed and synthesized a multifunctional mesoporous silica nanoparticle (MSN)-based boron-containing agent. The latter was coated with a lipid bilayer (LB) and decorated with SP94 peptide (SFSIIHTPILPL) on the surface as SP94-LB@BA-MSN. The latter incorporated boric acid (BA) into hydrophobic mesopores, coated with an LB, and modified with SP94 peptide on the LB. SP94-LB@BA-MSN enhanced nano interface tumor-targeting ability but also prevented the premature release of drugs, which is crucial for BNCT because adequate boron content in tumor sites is required. SP94-LB@BA-MSN showed excellent efficacy in the BNCT treatment of HepG-2 cells. In animal studies with tumor-bearing mice, SP94-LB@BA-MSN exhibited a satisfactory accumulation at the tumor site. The boron content reached 40.18 ± 5.41 ppm in the tumor site 4 h after injection, which was 8.12 and 15.51 times higher than those in mice treated with boronated phenylalanine and those treated with BA. For boron, the tumor-to-normal tissue ratio was 4.41 ± 1.13 and the tumor-to-blood ratio was 5.92 ± 0.45. These results indicated that nanoparticles delivered boron to the tumor site effectively while minimizing accumulation in normal tissues. In conclusion, this composite (SP94-LB@BA-MSN) shows great promise as a boron-containing delivery agent for the treatment of hepatocellular carcinoma using BNCT. These findings highlight the potential of MSNs in the field of BNCT.

Organically Modified Mesoporous Silica Nanoparticles against Bacterial Resistance.

Bacterial antimicrobial resistance is posed to become a major hazard to global health in the 21st century. An aggravating issue is the stalled antibiotic research pipeline, which requires the development of new therapeutic strategies to combat antibiotic-resistant infections. Nanotechnology has entered into this scenario bringing up the opportunity to use nanocarriers capable of transporting and delivering antimicrobials to the target site, overcoming bacterial resistant barriers. Among them, mesoporous silica nanoparticles (MSNs) are receiving growing attention due to their unique features, including large drug loading capacity, biocompatibility, tunable pore sizes and volumes, and functionalizable silanol-rich surface. This perspective article outlines the recent research advances in the design and development of organically modified MSNs to fight bacterial infections. First, a brief introduction to the different mechanisms of bacterial resistance is presented. Then, we review the recent scientific approaches to engineer multifunctional MSNs conceived as an assembly of inorganic and organic building blocks, against bacterial resistance. These elements include specific ligands to target planktonic bacteria, intracellular bacteria, or bacterial biofilm; stimuli-responsive entities to prevent antimicrobial cargo release before arriving at the target; imaging agents for diagnosis; additional constituents for synergistic combination antimicrobial therapies; and aims to improve the therapeutic outcomes. Finally, this manuscript addresses the current challenges and future perspectives on this hot research area.

Cu2+-pyropheophorbide-a-cystine conjugate-mediated multifunctional mesoporous silica nanoparticles for photo-chemodynamic therapy/GSH depletion combined with immunotherapy cancer

Photodynamic therapy (PDT) and chemodynamic therapy (CDT) can activate immunogenicity, so PDT and CDT combined immunotherapy is a promising treatment strategy. However, insufficient hydrogen peroxide activity, hypoxia, and overexpressed glutathione in the tumor microenvironment (TME) significantly impaired the ability to activate immunogenicity. Thus, in this paper, self-reinforcing conjugates Cu2+-Pyropheophorbide-a-Cysteine (CuPPaCC), combined synergetic NIR and pH triggered PDT/CDT with glutathione depletion ability was constructed. CuPPaCC was encapsulated in mesoporous silica, and spherical HSCuPPaCC nanoparticles were prepared by Hyaluronic acid (HA) on the silica surface by Schiff base modification. HSCuPPaCC has tumor-specific targeting via HA mediated. In acidic solution, the Schiff base of HSCuPPaCC is destroyed and CuPPaCC is released (>70%), with excellent pH response release function. The results of the MTT analysis showed that the PDT/CDT synergistic anti-tumor effect was significant. HSCuPPaCC was activated in TME, catalyzing the decomposition of hydrogen peroxide to generate hydroxyl radicals and oxygen, alleviating TME hypoxia, replenishing oxygen to PDT, and significantly down regulating hypoxia factor HIF-1α expression. HSCuPPaCC has an excellent dual ROS mechanism and a dual depleting GSH mechanism resulting in a surge in intracellular ROS levels to efficiently kill cancer cells, enhance the ability to induce immunogenicity, and make tumors more sensitive to checkpoint PD-L1 blockade therapy. With the CT26 mouse model, not only the primary tumor was eradicated, but also the distal tumor at the end of treatment was completely suppressed by HSCuPPaCC combined with anti-PD-L1 immune checkpoint blockade therapy.

Biodegradable nanoparticles-mediated targeted drug delivery achieves trans-spatial immunotherapy

Immunotherapy has been seriously retarded due to inadequate antigen presentation and a tumor cell-dominated immunosuppressive microenvironment (TME). Herein, biodegradable multifunctional mesoporous silica nanoparticles, with dispersed carbon nanodots incorporated into the frameworks, active TKD peptide modification on the surfaces and hydrophobic drug loading in the pores, were prepared for targeted chemotherapy synergized with trans-spatial immunotherapy. The nanoparticles were biodegradable due to nanodot-induced framework swelling, which would (1) kill the in situ tumor cells and promote antigen release by targeted chemotherapy and (2) trigger biodegraded debris involving TKD and CDs to largely adsorb the tumor antigens via π-π conjugation synergized hydrophobic interactions and then massively transport these antigens from the tumor cell-dominated TME to the immune cell-dominated spleen via TKD-mediated small size effects. Thereafter, these antigens can be processed into antigen peptides via TKD-mediated lysosome endocytosis and then activate T cells in the spleen via MHC complex construction and dendritic cell cytomembrane presentation. Therefore, improved immunotherapy with trans-spatial antigen presentation avoided TME immunosuppression, which when synergized with targeted chemotherapy, markedly enhanced the therapeutic outcomes of triple-negative breast cancer.

Multifunctional Mesoporous Silica Nanoparticles Reinforced Silk Fibroin Composite with Antibacterial and Osteogenic Effects for Infectious Bone Rehabilitation

Existing implant materials cannot meet the essential multifunctional requirements of repairing infected bone defects, such as antibacterial and osteogenesis abilities. A promising strategy to develop a versatile biomimicry composite of the natural bone structure may be accomplished by combining a multifunctional nanoparticle with an organic scaffold. In this study, a quaternary ammonium silane-modified mesoporous silica containing nano silver (Ag@QHMS) was successfully synthesized and further combined with silk fibroin (SF) to fabricate the multifunctional nano-reinforced scaffold (SF-Ag@QHMS) using the freeze-drying method. Furthermore, the antibacterial and osteogenic effects of this composite were evaluated in vitro and in vivo. SF-Ag@QHMS inherited a three-dimensional porous structure (porosity rate: 91.90 ± 0.62%) and better mechanical characteristics (2.11 ± 0.06 kPa) than that of the SF scaffold (porosity rate: 91.62 ± 1.65%; mechanic strength: 2.02 ± 0.01 kPa). Simultaneously, the introduction of versatile nanoparticles has provided the composite with additional antibacterial ability against Porphyromonas gingivalis, which can be maintained for 15 days. Furthermore, the expression of osteogenic-associated factors was up-regulated due to the silver ions eluting from the composite scaffold. The in vivo micro-CT and histological results indicated that the new bone formation was not only localized around the border of the defect but also arose more in the center with the support of the composite. The multifunctional silver-loaded mesoporous silica enhanced the mechanical strength of the composite while also ensuring greater and sustained antibacterial and osteogenic properties, allowing the SF-Ag@QHMS composite to be used to repair infected bone defects.

Tumor Suppression via Visually Derailing Intracellular Sialylation With Multifunctional Nanoparticles

Sialylation plays important roles in tumor-related physiological process. Therefore, intervention of sialylation has great potential to explore new paths for tumor therapy. In view of the immune modulation of sialic acid (SA) on tumor, this work designs a multifunctional mesoporous silica nanoparticle (MFMSN) to derail intracellular sialylation for tumor suppression. The galactose groups covered on MFMSN act as sialylation substrates to bind intracellular SAs competitively, which inhibits the SA expression on tumor cell surface. The derailed intracellular sialylation can be visualized on living cells and in vivo by specifically binding the sialylated galactose with phenylboronic acid labeled ssDNA probe released from the pore of MFMSN to induce DNA strand displacement, which recovers the fluorescence of dsDNA probe covered on MFMSN surface. The derailment of sialylation efficiently suppresses tumor growth on mice, demonstrating the great potentials of the designed strategy for revealing SA-related biological processes and clinical cancer therapy.

Mesoporous Silica Based Nanostructures for Bone Tissue Regeneration

Porous nano-scaffolds provide for better opportunities to restore, maintain, and improve functions of damaged tissues and organs by facilitating tissue regeneration. Various nanohybrids composed of mesoporous silica nanoparticles (MSNs) are being widely explored for tissue engineering. Since biological activity is enhanced by several orders of magnitude in multicomponent scaffolds, remarkable progress has been observed in this field, which has aimed to develop the controlled synthesis of multifunctional MSNs with tuneable pore size, efficient delivering capacity of bioactive factors, as well as enhanced biocompatibility and biodegradability. In this review, we aim to provide a broad survey of the synthesis of multifunctional MSN based nanostructures with exotic shapes and sizes. Further, their promise as a novel nanomedicine is also elaborated with respect to their role in bone tissue engineering. Also, recent progress in surface modification and functionalization with various polymers like poly (l-lactic acid)/poly (ε-caprolactone), polylysine-modified polyethylenimine, poly (lactic-co-glycolic acid), and poly (citrate-siloxane) and biological polymers like alginate, chitosan, and gelatine are also covered. Several attempts for conjugating drugs like dexamethasone and β–estradiol, antibiotics like vancomycin and levofloxaci, and imaging agents like fluorescein isothiocyanate and gadolinium, on the surface modified MSNs are also covered. Finally, the scope of developing orthopaedic implants and potential trends in 3D bioprinting applications of MSNs are also discussed. Hence, MSNs based nanomaterials may serve as improved candidate biotemplates or scaffolds for numerous bone tissue engineering, drug delivery and imaging applications deserving our full attention now.

In vivo therapeutic evaluation of a novel bis-lawsone derivative against tumor following delivery using mesoporous silica nanoparticle based redox-responsive drug delivery system

Herein, we have evaluated the in vivo therapeutic efficacy and systemic toxicity profile of a synthetic anticancer compound [3,3′-((4-(trifluoromethyl)phenyl)methylene)bis(2-hydroxynaphthalene-1,4-dione)]. A multifunctional mesoporous silica nanoparticle (MSN) based drug delivery network was also fabricated which specifically showed targeting nature towards the cancer cell. The mesopores of silica nanoparticles were tagged with phenyl boronic acid (PBA) for targeted drug delivery into tumor tissue. 1j was then loaded inside the nanocarriers followed by pore blocking with gold nanoparticles (GN) to attain a redox-responsive controlled drug delivery pattern. The synthesized nanocarriers (1j@-MSN-PBA-GN) having mean diameter of ~86 nm exhibited a moderate 1j loading content of 13.68% with overall negative surface charge. Both the targeted and non-targeted nanoformulations were tested for their anticancer activities both in vitro and in vivo models, and found more effective as compared with free 1j treatment. However, the targeted nanoformulations showed higher therapeutic effect due to increased cellular internalization and caused mitochondria-dependent apoptosis in MCF-7 cells via oxidative stress. Besides, the targeted nanoformulation significantly inhibited in the development of solid tumor in comparison to non-targeted nanoformulations and free 1j as a consequence of increased internalization of the drug-candidate in tumor tissue. Therefore, this study proposes that 1j can be considered as a potent anti-carcinogenic compound in vivo and its therapeutic potential is further increased by using PBA functionalized and GN gated MSN-based controlled drug delivery system without showing any significant systemic toxicity.

Magnetism, Ultrasound, and Light-Stimulated Mesoporous Silica Nanocarriers for Theranostics and Beyond.

Stimuli-responsive multifunctional mesoporous silica nanoparticles (MSNs) have been studied intensively during the past decade. A large variety of mesopore capping systems have been designed, initially to show that it could be done and later for biomedical applications such as drug delivery and imaging. On-command release of cargo molecules such as drugs from the pores can be activated by a variety of stimuli. This paper focuses on three noninvasive, biologically usable external stimuli: magnetism, ultrasound, and light. We survey the variety of MSNs that have been and are being used and assess capping designs and the advantages and drawbacks of the nanoplatforms' responses to the various stimuli. We discuss important recent advances, their basic mechanisms, and their requirements for stimulation. On the basis of our survey, we identify fundamental challenges and suggest future directions for research that will unleash the full potential of these fascinating nanosystems for clinical applications.

Mesoporous Silica Nanoparticles as pH-Responsive Carrier for the Immune-Activating Drug Resiquimod Enhance the Local Immune Response in Mice.

Nanoparticle-based delivery systems for cancer immunotherapies aim to improve the safety and efficacy of these treatments through local delivery to specialized antigen-presenting cells (APCs). Multifunctional mesoporous silica nanoparticles (MSNs), with their large surface areas, their tunable particle and pore sizes, and their spatially controlled functionalization, represent a safe and versatile carrier system. In this study, we demonstrate the potential of MSNs as a pH-responsive drug carrier system for the anticancer immune-stimulant R848 (resiquimod), a synthetic Toll-like receptor 7 and 8 agonist. Equipped with a biotin-avidin cap, the tailor-made nanoparticles showed efficient stimuli-responsive release of their R848 cargo in an environmental pH of 5.5 or below. We showed that the MSNs loaded with R848 were rapidly taken up by APCs into the acidic environment of the lysosome and that they potently activated the immune cells. Upon subcutaneous injection into mice, the particles accumulated in migratory dendritic cells (DCs) in the draining lymph nodes, where they strongly enhanced the activation of the DCs. Furthermore, simultaneous delivery of the model antigen OVA and the adjuvant R848 by MSNs resulted in an augmented antigen-specific T-cell response. The MSNs significantly improved the pharmacokinetic profile of R848 in mice, as the half-life of the drug was increased 6-fold, and at the same time, the systemic exposure was reduced. In summary, we demonstrate that MSNs represent a promising tool for targeted delivery of the immune modulator R848 to APCs and hold considerable potential as a carrier for cancer vaccines.

Multifunctional mesoporous silica nanoparticles with different morphological characteristics for in vitro cancer treatment

It has been widely reported that the shape of nanoparticles can significantly affect their nonspecific uptake into tumor cells. In this work, We prepared three different morphologies of mesoporous silica nanoparticles and explained the mechanism, and three types of multifunctional mesoporous silica nanoparticles with different morphological characteristics (DOX@MSN-x-PEG-FA) was first synthesized using rosin as an additive agent, and then constructed for targeted drug delivery systems (TDDS) carrying doxorubicin (DOX) as a model drug. The morphology and structural properties of these nanoparticles were characterized by means of SEM, TEM and N2 adsorption/desorption, and the biocompatibility of blank nanoparticles was evaluated by hemolysis assay. Utilizing the kinetic model, the loading and releasing mechanisms of DOX were also evaluated. The drug adsorption process is mainly carried out by chemical adsorption (covalent bonding), and the release process followed an anomalous (non-Fick) transport mechanism. These DOX@MSN-x-PEG-FA exhibited a pH-dependent and sustained drug release behavior which are the required properties for drug delivery systems. Compared to the other two samples, DOX@MSN-80-PEG-FA possessed the highest cell-targeted uptake capacity and apoptosis rate, indicating that it is a promising drug delivery system for cancer-targeted therapy.

Modification of Mesoporous Silica Surface by Immobilization of Functional Groups for Controlled Drug Release

This paper introduces the synthesis of mesoporous silica nanoparticles (MSNs) with three different groups such as amine, thiol, and sulfonic acid, along the internal surface. Trimethyl[3-(trimethoxysilyl)propyl]ammonium chloride was used to modify the external surface of the nanomaterials. Such materials allow control of the drug release from MSN pores. Multifunctional MSNs were loaded with doxycycline (Doxy) to study their capacities and uploading time. The loading profile indicates that sulfonic groups in the internal surface were the most efficient surfaces with a loading capacity of ca. 35% in 90 min in acidic media.

UV-light cross-linked and pH de-cross-linked coumarin-decorated cationic copolymer grafted mesoporous silica nanoparticles for drug and gene co-delivery in vitro.

The chemotherapy combined with gene therapy has emerged as a promising strategy for cancer therapy because of enhanced anticancer efficacy. To this end, we constructed a novel UV-light cross-linked and pH de-cross-linked coumarin-decorated cationic copolymer functionalized mesoporous silica nanoparticles (MSN) for co-delivery of chemotherapeutic agent 5-FU and tumor suppresser p53 gene. The multifunctional MSN were modified with poly(glycidyl methacrylate)-b-poly(2-(dimethylamino)ethyl methacrylate) (PGMA-b-PDMAEMA) via two sequential surface-initiated atom transfer radical polymerization (ATRP), followed by ring-opening of epoxy groups with ethanediamine and covalent conjugation with coumarin moieties via acid-liable cis-aconityl bonds. The in vitro drug release results indicated that the premature release was negligible at physiological pH when coumarin moieties on the MSN-g-PCAAMC-b-PDMAEMA surface underwent UV-light induced photo-dimerization (cross-linking), while the release of embedded drugs was accelerated under acidic conditions, which was attributed to the hydrolytic cleavage of cis-aconityl bonds (de-crosslinking). In addition to small-molecule drug, the established MSN-g-PCAAMC-b-PDMAEMA also could carry p53 gene in outer cationic copolymers, and the formed complex exhibited good gene transfection activity. Interestingly, coumarin moieties themselves could emit blue fluorescence, which was used to track the cellular uptake of the nanocarriers without the need of additional fluorescence probes. Importantly, the cytotoxicity and cell apoptosis assays confirmed that co-delivery of 5-FU and p53 gene by the cross-linked MSN-g-PCAAMC-b-PDMAEMA@5-FU/p53 induced enhanced chemotherapeutic efficacy as compared to 5-FU delivery alone. In conclusion, these results suggested that the constructed stimuli-responsive co-delivery system may hold the promise for cancer therapeutic application.

Multifunctional Mesoporous Silica Nanoparticles for Cancer Therapy and Imaging

Cancer is a widespread disease and has a high mortality rate. Popular conventional treatment encompasses chemotherapy, radiation and surgical resection. However, these treatments impart lots of toxicity problems to the patients mostly due to their non-selectiveness nature, which invokes drug resistances and severe side-effects. In this regard, nanotechnology has claimed to be a smart technology that provides the system with the ability to target drugs to the specific sites. With the use of nanotechnology, various nanomaterials that are widely used as a drug delivery vehicle are created for biomedical applications. Amongst variously diversified nanovehicles, mesoporous silica nanoparticles (MSNs) have attracted enormous attention due to their structural characteristics, great surface areas, tunable pore diameters, good thermal and chemical stability, excellent biocompatibility along with ease of surface modification. Furthermore, the drug release from MSNs can be tailored through various stimuli response gatekeeper systems. The ordered structure of MSNs is extremely suitable for loading of the high amount of drug molecules with controlled delivery for targeting the cancer tissues via enhanced permeability and retention effect or further with surface modification, it can also be actively targeted by various ligands. The review article emphases the common synthetic methods and current advancement of MSNs usages for stimuli response drug delivery, immunotherapy as well as the theranostic ability for cancer. Although MSNs are becoming the promising tool for more efficient and safer cancer therapy, however, additional translational studies are required to explore its multifunctional ability in a clinical setting.

A Dual-Model Imaging Theragnostic System Based on Mesoporous Silica Nanoparticles for Enhanced Cancer Phototherapy.

Mesoporous silica nanoparticles (MSNs) show great promise to be exploited as versatile multifunctional nanocarriers for effective cancer diagnosis and treatment. In this work, perfluorohexane (PFH)-encapsulated MSNs with indocyanine green (ICG)-polydopamine (PDA) layer and poly(ethylene glycol)-folic acid coating (designated as MSNs-PFH@PDA-ICG-PEG-FA) are successfully fabricated to achieve tumor ultrasonic (US)/near-infrared fluorescence (NIRF) imaging as well as photothermal therapy (PTT)/photodynamic therapy (PDT). MSNs-PFH@PDA-ICG-PEG-FA exhibits good monodispersity with high ICG loading, significantly enhances ICG photostability, and greatly improves cellular uptake. Upon single 808 nm NIR irradiation, the nanocarrier not only efficiently generates hyperthermia to realize PTT, but also produces reactive oxygen species (ROS) for effective PDT. Meanwhile, NIR irradiation can trigger PFH to undergo vaporization and provide a super-resolution US image. Thus, the PTT/PDT combination therapy can be dually guided by PFH-induced US imaging and ICG-induced NIRF imaging. In vivo antitumor studies demonstrate that PTT/PDT from MSNs-PFH@PDA-ICG-PEG-FA significantly inhibits tumor growth and achieves a cure rate of 60% (three out of five mice are completely cured). Hence, the multifunctional MSNs appear to be a promising theragnostic nanoplatform for multimodal cancer imaging and therapy.

<p>Glucose-responsive mesoporous silica nanoparticles to generation of hydrogen peroxide for synergistic cancer starvation and chemistry therapy</p>

Background: The combination of novel starving therapy with chemotherapy is one of the most promising strategies to achieve an effective antitumor activity.Methods: Herein, we developed a multifunctional mesoporous silica nanoparticle (MSNs-GOx/PLL/HA) coated with poly (L-lysine) (PLL) and hyaluronic acid (HA) for co-delivery of glucose oxidase (GOx) and anticancer drug paclitaxel (PTX) for cancer treatment for the first time. Compared to single chemotherapy, introduction of GOx would not only selectively trigger the consumption of intracellular glucose, leading to the interruption of energy supply, but also elevat the endogenous H2O2 level, inducing stronger therapeutic effects.Results: The novel drug delivery system possessed desirable particle diameter of 40 nm and exhibited a pH-sensitive drug release behavior. An in vitro cellular uptake study indicated that MSNs-GOx/PLL/HA nanoparticles effectively enhanced the cellular uptake of drug in an apparently CD44 receptor-dependent manner, and delivered more cargo into cytoplasm via endolysosomal escape effect in presence of PLL. The nanoplatform has also demonstrated amplified synergistic therapeutic effects for remarkable tumor inhibition in a xenograft animal tumor model.Conclusion: Consequently, the developed synergistic starving-like/chemotherapy may provide a potential platform for next generation cancer therapy.

Stable mesoporous silica nanoparticles incorporated with MoS2 and AIE for targeted fluorescence imaging and photothermal therapy of cancer cells.

Theranostics for imaging-guided cancer treatment have obtained great attention in recent years for their outstanding capability of both tumor diagnosis and treatment. Molybdenum disulfide (MoS2) nanosheets revealed excellent photothermal conversion efficiency, which could be used as photothermal agents. However, MoS2 nanosheets would often quench or decrease the emission of fluorescence dyes when they were incorporated with these dyes to construct fluorescence-imaging-guided nanotheranostic systems. In this work, MoS2 nanosheets were embedded into mesoporous silica nanoparticles (MSNs), and Aggregation Induced Emission (AIE) fluorogen PhENH2 was chemically modified on the surface of MSNs, which could demonstrate more stable fluorescence emission compared with other MSNs with physically absorbed luminescent molecules. Moreover, folic acid (FA) was also chemically decorated on the nanoparticles to facilitate their targeted bioimaging and photothermal therapy. As expected, the obtained PhENH2-MoS2-FA MSNs could be efficiently taken up by MDA-MB-231 cells than HepG2 cells, owing to the over-expressed FA receptors on MDA-MB-231 cells. Meanwhile, these MDA-MB-231 cells could be efficiently killed under an 808 nm laser irradiation. These results indicated that the achieved multifunctional MSNs chemically decorated with AIE fluorogens would demonstrate more stable fluorescence for bioimaging-targeted photothermal therapy of MDA-MB-231 cells, which made them promising nanotheranostics for further cancer treatment.

Tracking embryonic hematopoietic stem cells to the bone marrow: nanoparticle options to evaluate transplantation efficiency

BackgroundAs the prevalence of therapeutic approaches involving transplanted cells increases, so does the need to noninvasively track the cells to determine their homing patterns. Of particular interest is the fate of transplanted embryonic stem cell-derived hematopoietic progenitor cells (HPCs) used to restore the bone marrow pool following sublethal myeloablative irradiation. The early homing patterns of cell engraftment are not well understood at this time. Until now, longitudinal studies were hindered by the necessity to sacrifice several mice at various time points of study, with samples of the population of lymphoid compartments subsequently analyzed by flow cytometry or fluorescence microscopy. Thus, long-term study and serial analysis of the transplanted cells within the same animal was cumbersome, making difficult an accurate documentation of engraftment, functionality, and cell reconstitution patterns.MethodsHere, we devised a noninvasive, nontoxic modality for tracking early HPC homing patterns in the same mice longitudinally over a period of 9 days using mesoporous silica nanoparticles (MSNs) and magnetic resonance imaging.ResultsThis approach of potential translational importance helps to demonstrate efficient uptake of MSNs by the HPCs as well as retention of MSN labeling in vivo as the cells were traced through various organs, such as the spleen, bone marrow, and kidney. Altogether, early detection of the whereabouts and engraftment of transplanted stem cells may be important to the overall outcome. To accomplish this, there is a need for the development of new noninvasive tools.ConclusionsOur data suggest that multifunctional MSNs can label viably blood-borne HPCs and may help document the distribution and homing in the host followed by successful reconstitution.

Curcumin polymer coated, self-fluorescent and stimuli-responsive multifunctional mesoporous silica nanoparticles for drug delivery

We reported the facile preparation of self-fluorescent mesoporous silica nanoparticles based on a triple-role curcumin polymer shell as stimuli-responsive multifunctional nanocarriers for drug delivery. This curcumin polymer shell integrates multiple function of acting as fluorescent agents, increasing the drug loading ratio of curcumin, and controlling the open and close of the pores in a “smart” way. This novel drug nanocarrier will inspire the development of smart and self-fluorescent drug nanocarrier to achieve imaging and therapeutic goals for cancer therapy.

Targeted and controlled drug delivery by multifunctional mesoporous silica nanoparticles with internal fluorescent conjugates and external polydopamine and graphene oxide layers

This study demonstrated the targeted delivery and controlled release of cisplatin drug molecules from doubly decorated mesoporous silica nanoparticles (MSNs), which were internally grafted with fluorescent conjugates and externally coated with polydopamine (PDA) and graphene oxide (GO) layers. The brush-like internal conjugates conferred fluorescent functionality and high capacity of cisplatin loading into MSNs, as well as contributing to a sustained release of the cisplatin through a porous channel with the assistance of external PDA layer. A consolidated double-layer formed by electrostatic interactions between the GO nanosheet and the PDA layer induced more controlled release kinetics which was well predicted by Higuchi model. In addition, Our MSNs exhibited stimuli (pH, NIR irradiation)-responsive controlled release as a potential chemo-photothermal agent against cancer cells. In a cell test, multifunctional MSNs showed a low toxicity itself, but gave a high cytotoxicity against human epithelial neuroblastoma cells (SH-SY5Y) after loading cisplatin. Notably, GO-wrapped MSNs exhibited very effective drug delivery because GO wrapping enhanced their dispensability in aqueous solution, photothermal heating effect, and efficient endocytosis into cells. Furthermore, monoclonal antibody (anti-human epidermal growth factor receptor)-conjugated MSNs showed a higher specificity, which resulted in more enhanced anticancer effects in vitro. The current study demonstrated a reliable synthesis of multifunctional MSNs, endowed with fluorescent imaging, stimuli-responsive controlled release, higher specificity, and efficient cytotoxicity toward cancer cells. Statement of SignificanceThe current study demonstrated the reliable synthesis of multifunctional mesoporous silica nanoparticles (MSNs) with internal fluorescent conjugates and external polydopamine and graphene oxide (GO) layers. The combination of internal conjugates and external coating layers produced an effective pore closure effect, leading to controlled and sustained release of small drug molecules. Notably, GO wrapping improved the dispensability and cellular uptake of the MSNs, as well as enhanced drug-controlled release. Our multifunctional MSNs revealed very efficient drug delivery effects against human epithelial neuroblastoma cells by demonstrating several strengths: i) fluorescent imaging, ii) sustained and controlled release of small drug molecules, iii) efficient cellular uptake, cytotoxicity and specificity, and v) stimuli (pH, NIR irradiation)-responsive controlled release as a potential chemo-photothermal agent.