Dual responsive block copolymer coated hollow mesoporous silica nanoparticles for glucose-mediated transcutaneous drug delivery

A self-regulated anti-diabetic drug release device mimicking pancreatic cells is highly desirable for the therapy of diabetes. Herein, a glucose-mediated dual-responsive drug delivery system, which combines pH-and H_(2)O_(2)-responsive block copolymer grafted hollow mesoporous silica nanoparticles(HMSNs)with microneedle(MN) array patch, has been developed to achieve self-regulated administration.The poly[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acrylate]-b-poly[2-(dimethylamino)ethyl methacrylate](PPBEM-b-PDM) polymer serves as gate keeper to prevent drug release from the cavity of HMSNs at normoglycemic level. In contrast, the drug release rate is significantly enhanced upon H_(2)O_(2)and pH stimuli due to the chemical change of H_(2)O_(2)sensitive PPBEM block and acid responsive PDM block. Therefore, incorporation of anti-diabetic drug and glucose oxidase(GOx, which can oxidize glucose to gluconic acid and in-situ produce H_(2)O_(2)) into stimulus polymer coated HMSNs results in a glucose-mediated MN device after depositing the drug-loaded nanoparticles into MN array patch. Both in vitro and in vivo results show this MN device presents a glucose mediated self-regulated drug release characteristic, which possesses a rapid drug release at hyperglycemic level but retarded drug release at normoglycemic level. The result indicates that the fabricated smart drug delivery system is a good candidate for the therapy of diabetes.

Bioinspired Hollow Mesoporous Silica Nanoparticles Coating on Titanium Alloy with Hierarchical Structure for Modulating Cellular Functions

3D-printed Porous Titanium Alloy Implants(pTi),owing to their biologically inertness and relatively smooth surface morphology,adversely affect the biological functions of surrounding cells.To address the challenges,constructing a bioinspired interface that mimics the hierarchical structure of bone tissue can enhance the cellular functions of cells.In this context,Hollow Mesoporous Silica Nanoparticles(HMSNs),renowned for their unique physicochemical properties and superior biocompatibility,offer a promising direction for this research.In this research,the initially synthesized HMSNs were used to construct a“hollow-mesoporous-macroporous”hierarchical bioinspired coating on the pTi surface through the Layer-by-Layer technique.Simultaneously,diverse morphologies of coatings were established by adjusting the deposition strategy of PDDA/HMSNs on the pTi surface(pTi-HMSN-2,pTi-HMSN-4,pTi-HMSN-6).A range of techniques were employed to investigate the physicochemical properties and regulation of cellular biological functions of the diverse HMSN coating strategies.Notably,the pTi-HMSN-4 and pTi-HMSN-6 groups exhibited the uniform coatings,leading to a substantial enhancement in surface roughness and hydrophilicity.Meantime,the coating constructed strategy of pTi-HMSN-4 possessed commendable stability.Based on the aforementioned findings,both pTi-HMSN-4 and pTi-HMSN-6 facilitated the adhesion,spreading,and pseudopodia extension of BMSCs,which led to a notable upsurge in the expression levels of vinculin protein in BMSCs.Comprehensive analysis indicates that the coating,when PDDA/HMSNs are deposited four times,possesses favorable overall performance.The research will provide a solid theoretical basis for the translation of HMSN bioinspired coatings for orthopedic implants.

Hollow mesoporous silica nanoparticles as nanocarriers employed in cancer therapy: A review

Hollow mesoporous silica nanoparticles(HMSNs)have become an attractive drug carrier because of their unique characteristics including stable physicochemical properties,large specific surface area and facile functionalization,especially made into intelligent drug delivery systems(DDSs)for cancer therapy.HMSNS are employed to transport traditional anti-tumor drugs,which can solve the problems of drugs with instability,poor solubility and lack of recognition,etc.,while significantly improving the anti-tumor effect.And an unexpected good result will be obtained by combining functional molecules and metal species with HMSNs for cancer diagnosis and treatment.Actually,HMSNs-based DDSS have developed relatively mature in recent years.This review briefly describes how to successfully prepare an ordinary HMSNs-based DDS,as well as its degradation,different stimuli-responses,targets and combination therapy.These versatile intelligent nanoparticles show great potential in clinical aspects.

Polymer-grafted hollow mesoporous silica nanoparticles integrated with microneedle patches for glucose-responsive drug delivery

A glucose-mediated drug delivery system would be highly satisfactory fordiabetes diagnosis since it can intelligently release drug based on blood glucose levels.Herein,a glucose-responsive drug delivery system by integrating glucose-responsivepoly(3-acrylamidophenylboronic acid)(PAPBA)functionalized hollow mesoporous silicananoparticles(HMSNs)with transcutaneous microneedles(MNs)has been designed.Thegrafted PAPBA serves as gatekeeper to prevent drug release from HMSNs atnormoglycemic levels.In contrast,faster drug release is detected at a typicalhyperglycemic level,which is due to the change of hydrophilicity of PAPBA at highglucose concentration.After transdermal administration to diabetic rats,an effectivehypoglycemic effect is achieved compared with that of subcutaneous injection.Theseobservations indicate that the designed glucose-responsive drug delivery system has apotential application in diabetes treatment.

In Vivo Tumor-Targeted Dual-Modality PET/Optical Imaging with a Yolk/Shell-Structured Silica Nanosystem

Silica nanoparticles have been one of the most promising nanosystems for biomedical applications due to their facile surface chemistry and non-toxic nature. However, it is still challenging to effectively deliver them into tumor sites and noninvasively visualize their in vivo biodistribution with excellent sensitivity and accuracy for effective cancer diagnosis. In this study, we design a yolk/shell-structured silica nanosystem ^(64) Cu-NOTAQD@HMSN-PEG-TRC105, which can be employed for tumor vasculature targeting and dual-modality PET/optical imaging, leading to superior targeting specificity, excellentimaging capability and more reliable diagnostic outcomes.By combining vasculature targeting, pH-sensitive drug delivery, and dual-modality imaging into a single platform,as-designed yolk/shell-structured silica nanosystems may be employed for the future image-guided tumor-targeted drug delivery, to further enable cancer theranostics.

Dual-stimuli responsive near-infrared emissive carbon dots/hollow mesoporous silica-based integrated theranostics platform for real-time visualized drug delivery

Due to better penetrating abilities of near-infrared (NIR) light and lower autofluorescence of biological tissue at NIR region, the combination of NIR fluorescent imaging with therapeutic abilities has gradually emerged as a promising strategy for cancer therapy. Herein, tumor microenvironment (TME) sensitive nanocarriers based on doxorubicin hydrochloride (DOX), NIR emitting carbon dots (C-dots), hollow mesoporous silica nanoparticles (HMSN) and anionic polymer citraconic anhydride-modified polylysine (PLL(cit)) are fabricated for imaging guided drug delivery. The NIR emitting C-dots were conjugated onto the surface of HMSN via disulfide bonds which can be reduced by intracellular glutathione (GSH) and result in the release of DOX into cells. And then the PLL(cit) was grafted on the surface of the nanocarriers to endow the nanocarriers with charge convertible property in mildly acidic TME (pH = 6.50) which results in prolonged blood circulation time and enhanced cellular internalization. The in vitro and in vivo experiments confirmed that the dual pH/GSH responsive features of nanocarriers can eliminate the tumor tissues effectively and elicit much slighter side effects. Moreover, since the fluorescence of C-dots can be recovered after the reduction of disulfide bonds and selectively accumulation of nanocarriers around tumor tissue, the DOX@HMSN-SS-C-dots-PLL(cit) can be served as a promising NIR fluorescence probe for targeted imaging of tumor tissue. As a kind of multifunctional nanocarrier with NIR fluorescent imaging and therapeutic functions, the theranostic nanocarriers hold great potential for tumor therapy and in vivo imaging of tumor tissue.

Phenylboronic acid-modified hollow silica nanoparticles for dual-responsive delivery of doxorubicin for targeted tumor therapy

This work reports a multifunctional nanocarrier based on hollow mesoporous silica nanoparticles(HMSNs)for targeting tumor therapy.Doxorubicin(DOX)was loaded into HMSNs and blocked with cytochrome C conjugated lactobionic acid(CytC–LA)via redox-cleavable disulfide bonds and pH-disassociation boronate ester bonds as intermediate linkers.The CytC–LA was used both as sealing agent and targeting motif.A series of characterizations demonstrated the successful construction of the drug delivery system.The system demonstrated pH and redox dual-responsive drug release behavior in vitro.The DOX loading HMSNs system displayed a good biocompatibility,which could be specifically endocytosed by HepG2 cells and led to high cytotoxicity against tumor cells by inducing cell apoptosis.In vivo data(tumor volume,tumor weight,terminal deoxynucleotidyl transferase dUTP nick end labeling and hematoxylin and eosin staining)proved that the system could deliver DOX to tumor site with high efficiency and inhibit tumor growth with minimal toxic side effect.

Camptothecin@HMSNs/thermosensitive hydrogel composite for applications in preventing local breast cancer recurrence

Camptothecin has a strong tumor killing ability for a variety of tumor cells with its special anti-cancer mechanism including the breast cancer. However, because of its infinite hydrophobic property, its clinical application has been greatly limited. Early prevention of loco regional recurrence for the breast cancer is critical for patients who have undergone breast-conserving therapy. In the study,CPT was used for the inhibition of the recurrence after the operation. The hollow mesoporous silica nanoparticles were used as the carrier to improve the hydrophilic property and increase its bioavailability with the high loading capacity. The ability of the cellular uptake and antitumor activity was increased. Hydrogel was the ideal carrier for local therapy, so the CPT@HMSNs were loaded into the PLEL thermo sensitive hydrogel to be injected into the tumor sites after the tumor was resected. The recurrence was reduced in the group of CPT-HMSNs-PLEL and the side effect of CPT was decreased. They exhibit distinguished potential as drug carrier for local delivery.