Mesoporous Silicon Research Articles

A Biomimetic Nanocarrier Strategy Targets Ferroptosis and Efferocytosis During Myocardial Infarction.

Myocardial infarction (MI) is characterized by irreversible cardiomyocyte death resulting from an inadequate supply of oxygenated blood to the myocardium. Recent studies have indicated that ferroptosis, a form of regulated cell death, exacerbates myocardial injury during MI. Concurrently, the upregulation of CD47 on the surface of damaged myocardium following MI impairs the clearance of dead cells by macrophages, thereby hindering efferocytosis. In this context, simultaneously inhibiting ferroptosis and enhancing efferocytosis may represent a promising strategy to mitigate myocardial damage post-MI. In this study, we engineered platelet membrane-coated hollow mesoporous silicon nanoparticles (HMSN) to serve as a drug delivery system, encapsulating ferroptosis inhibitor, Ferrostatin-1, along with an anti-CD47 antibody. We aimed to assess the potential of these nanoparticles (designated as Fer-aCD47@PHMSN) to specifically target the site of MI and evaluate their efficacy in reducing cardiomyocyte death and inflammation. The platelet membrane coating on the nanoparticles significantly enhanced their ability to successfully target the site of myocardial infarction (MI). Our findings demonstrate that treatment with Fer-aCD47@PHMSN resulted in a 38.5% reduction in cardiomyocyte ferroptosis under hypoxia, indicated by decreased lipid peroxidation and increased in vitro. Additionally, Fer-aCD47@PHMSN improved cardiomyocyte efferocytosis by approximately 15% in vitro. In MI mice treated with Fer-aCD47@PHMSN, we observed a substantial reduction in cardiomyocyte death (nearly 30%), decreased inflammation, and significant improvement in cardiac function. Our results demonstrated that the cooperation between the two agents induced anti-ferroptosis effects and enhanced dead cardiomyocyte clearance by macrophage as well as anti-inflammation effects. Thus, our nanoparticle Fer-aCD47@PHMSN provides a new therapeutic strategy for targeted therapy of MI.

Stable "snow lantern-like" aggregates of silicon nanoparticles suitable as a drug delivery platform.

Nanomedicine is a growing field where development of novel organic and inorganic materials is essential to meet the complex requirements for drug delivery. This includes biocompatibility, suitability for surface modifications, biodegradability, and stability sufficient to carry a drug payload through various tissues for the desired timespan. Porous silicon nanoparticles (pSi NP) are shown to have several beneficial traits in drug delivery in addition to a porous structure to maximize drug loading. The conventional synthesis of pSi NP using electrochemical etching is costly, time-consuming and requires large quantities of highly toxic hydrofluoric acid (HF). As such this research attempted a novel method to address these limitations. Mesoporous silicon nanoparticles were prepared by centrifugal Chemical Vapor Deposition (cCVD) without the use of HF. This process generated aggregates consisting of multiple primary particles fused into each other, similar to snowballs fused together in a snow-lantern (snowball pyramid). Our results demonstrated that the cCVD Si particles were versatile in terms of surface chemistry, colloidal stability, degradability, minimization of acute in vitro toxicity, and modulation of drug release. Dynamic light scattering, scanning electron microscopy, and cryogenic nitrogen adsorption isotherm measurements confirmed the overall size (210 nm), morphology, and pore size (14-16 nm) of the prepared materials. Agglomeration in phosphate-buffered saline (PBS) was minimized by PEGylation by a two-step grafting procedure that employed a primary amine linker. Finally, the release rate of a model drug, hydrocortisone, was evaluated with both PEGylated and pristine particles. Conclusively, these snow-lantern cCVD Si particles do indeed appear suitable for drug delivery.

다공성의 콜로이드성 이산화규소를 이용한 닐로티닙 함유 고형의 자가미세유화 약물전달시스템의 개발

The objective of this study was to develop a novel nilotinib HCl-loaded solidified self-nanoemulsifying drug delivery system (SNEDDS) formulation with enhanced solubility and dissolution rate. Various oils and surfactants were screened, resulting in the selection of Peceol (oil) and Tween 80 (surfactant) and Transcutol P (co-surfactant). Pseudoternary phase diagram was constructed to detect the nanoemulsion zone. Among the SNEDDS formulations tested, the SNEDDS consisting of Peceol (oil), Tween 80 (surfactant), and Transcutol P (co-surfactant) at a weight ratio of 30/50/20 produced an emulsion droplet size of 182.1±1.0 nm. The spray drying technique, using mesoporous silicon dioxide as an inert carrier, was employed to solidify the selected nilotinib HCl-loaded SNEDDS. The resulting nilotinib HCl-loaded solid SNEDDS (S-SNEDDS) was characterized by scanning electron microscopy (SEM), powder X-ray diffractometry (PXRD), dynamic light scattering, saturation solubility and in vitro dissolution study. The S-SNEDDS produced an emulsion droplet size of 185.2±0.9 nm and there was no change in emulsion particle size upon the addition of drug. SEM and PXRD results suggested that nilotinib HCl existed in an amorphous form in nilotinib HCl-loaded S-SNEDDS. Solubility tests across various pH levels showed a significant improvement in nilotinib HCl solubility. Similarly, dissolution tests demonstrated enhanced dissolution rates in all tested solutions, consistent with the solubility results. These results indicate that the employed methodologies were effective in increasing both the solubility and dissolution rates of nilotinib HCl across different pH environments, suggesting a successful enhancement of its bioavailability.

Assessing the production of galactooligosaccharides in batch and continuous mode by using β‐galactosidase immobilised on mesoporous silicon dioxide nanoparticles

SummaryThe present study evaluated the production of galactooligosaccharides (GOSs) from lactose in both batch and continuous modes using nano‐immobilised β‐galactosidase. Mesoporous silicon dioxide nanoparticles were used to immobilise β‐galactosidase to enhance the stability and production of GOSs. The change in enzyme‐characteristics was assessed using Fourier‐transform infrared and scanning electron microscope analysis. The nano‐immobilisation increased the enzyme's substrate affinity, but decreased its hydrolytic activity. A significant increase (P < 0.05) in stability was observed across a wide range of temperature (30 °C–70 °C) and pH (5.0–8.0). Both forms of enzymes (free and nano‐immobilised enzymes) followed the zero‐order reaction in all temperatures, while the nano‐immobilised enzyme had the highest activation energy. The free and nano‐immobilised enzymes retained 64.65% and 77.82% of their initial activity after 90 days of storage, respectively. In a batch mode, the nano‐immobilised enzyme produced 2.35 times more GOSs than the free enzyme. The GOSs production remained consistent while the enzyme activity decreased by 12.7% after 5 cycles of operation. The continuous mode of production in a packed bed reactor achieved a GOSs yield of 16.92%. Overall, the nano‐immobilised enzyme showed better GOSs production under batch and continuous mode of operation.

Investigation of mesoporous silicon thermal conductivity: Effect of nanographene insertion

In this study, the impact of nanographene incorporation on the thermal properties of mesoporous silicon (PSi) was evaluated using two complementary experimental methods: the temperature gradient (TG) and the photothermal radiometry (MPTR) methods. It is shown that the measured thermal conductivity of the mesoporous silicon (PSi) ranges from 0.10 to 0.68 W/m.K in the case of TG and from 0.37 to 3.02 W/m.K in MPTR and is strongly correlated to the electrochemical etching parameters. These values are much lower than that of crystalline silicon, estimated to be from 100 to 140 W/m.K, depending on the doping rate. They appear to be, however, in the order of magnitude range for the percolation models that also include the in-depth porosity and the crystallite mean radius. This set of experiments on the thermal conductivity was extended to investigate the effect of graphene incorporation in the PSi matrix (G-PSi) as it has seldom been reported in the literature. The results from both methods exhibit significantly higher values (1.7 ± 0.3 W/m.K for TG, and from 0.7 to 2.13 W/m.K for MPTR). This spread of the thermal conductivity values is attributed to the intrinsic working principle of the TG versus the MPTR method as highlighted in the last part of the present paper. Targeting the thermoelectric application of both matrices (PSi, G-PSi), the thermal conductivity remains sufficiently low for them to be considered as very promising materials, keeping in mind the enhancement of the power-factor attributed to the incorporation of graphene.

Formation and morphological evolution investigation of the porous silicon decorated with Pt particles

Platinum nanoparticles were prepared on silicon substrates at room temperature using electroless deposition with different durations from 1 to 40 min. The effect of deposition times on the morphology and composition of the deposited Pt particles and porous films was examined using scanning, transmission electron microscopy, energy-dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, and Raman scattering. Moreover, atomic force microscopy was used to examine the structural properties and morphological characterization of the deposed particles. The wetting properties of the por-Si/Pt structure were investigated using the sessile drop method. The research indicates that the por-Si/Pt structure has uniformly distributed nonspherical self-assembled Pt particles with a height of up to 120 nm and a diameter of 200 nm. The concentration of these particles is 2.5 × 109 cm−2 and there is a mesoporous silicon layer with a thickness up to 580 nm. A uniform size distribution of the particles is achieved after 1 min of deposition. The conditions for creating the por-Si/Pt structure, characterized by a high Pt particle concentration and coverage, have been identified. The morphology parameters of the particles and layers depend on the duration of the deposition. The evolution of the formation of an array of platinum particles, meso- and macroporous silicon, including all stages of growth of the components of the Por-Si/Pt structure was established.

Preparation of nano-immobilised β-galactosidase using mesoporous silicon dioxide nanoparticles and its efficiency in production of galactooligosaccharides

The β-galactosidase (produced from Aspergillus oryzae) was immobilised on epichlorohydrin functionalised mesoporous silicon dioxide nanoparticles to produce galactooligosaccharides (GOS) from lactose. The characteristic amide bonds and increased particle size confirmed the adsorption of enzyme on nanoparticles. Nano-immobilisation resulted in an increase in enzyme affinity towards the substrate and its hydrolytic property. Free and nano-immobilised enzymes retained 58 and 77% of the original enzyme activity up to 90 days of storage, respectively. The nano-immobilised enzyme exhibited greater stability over a broad range of temperature (30–70 °C) and pH (5.0–8.0). The GOS yield obtained from nano-immobilised enzyme was 2.23 times higher than the free enzyme. GOS production was decreased by 90% and enzyme activity was reduced to 10% in a run of 5 cycles. Overall, the developed nano-immobilisation technique has potential to enhance the stability of the enzyme and GOS production.

Effect of different etching times on the structural, morphological, electrical, and antimicrobial properties of mesoporous silicon

The present work focuses on the structural, morphological, electrical characteristics, and antibacterial activity of mesoporous silicon (PS) against S. aureus and E. coli. We depict the structural and antimicrobial activity of PS as a result of different etching times (10.0, 20.0, 30.0, 40.0, 50.0, and 60.0 min) with a current density of 100 mA/cm2. The structural and morphological characteristics of synthesized PS have been examined with Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscopy (AFM). FTIR spectra have been used to confirmed the Si–O, Si–O–Si bond and the adsorption on the surface of PS nanoparticles. The formation of pores on the c-Si wafer results in an analysis of a photoluminescence (PL) band at 712 nm, which changes with etching time in a process similar to current density. The correlation exist among etching times and the ideality factor (η) and barrier height (фb). Gram-positive (S. aureus) and Gram-negative (E. coli) bacteria showed enhanced antimicrobial activity against the PS nanoparticles. The synthesized of PS has been shown with good electrical and antimicrobial activities.

Design of cost-effective environment-responsive nanoacoustic devices based on mesoporous thin films

Gigahertz acoustic resonators have the potential to advance data processing and quantum communication. However, they are expensive and lack responsiveness to external stimuli, limiting their use in sensing applications. In contrast, low-cost nanoscale mesoporous materials, known for their high surface-to-volume ratio, have shown promise in various applications. We recently demonstrated that mesoporous silicon dioxide (SiO2) and titanium dioxide (TiO2) thin layers can support coherent acoustic modes in the 5 to 100 GHz range. In this study, we propose a new method for designing tunable acoustic resonators using mesoporous thin films on acoustic distributed Bragg reflectors. By simulating the infiltration of the pores with water, we show that the material’s properties could be altered and achieve tunability in the acoustic resonances. We present four device designs and use simulations to predict resonators with Q-factors up to 1500. We also observe that the resonant frequency and intensity show a linear response to water infiltrated in the mesopores, with a tunability of up to 60%. Our platform offers a unique opportunity to design cost-effective nanoacoustic sensing and reconfigurable optoacoustic nanodevices.

Harnessing the Materials Chemistry of Mesoporous Silicon Nanoparticles to Prepare “Armor-Clad” Enzymes

Harnessing the Materials Chemistry of Mesoporous Silicon Nanoparticles to Prepare “Armor-Clad” Enzymes

The Deposition of Isolated Fe(3+) Species in Mesoporous Silicon for Oxidation of Cyclohexane

AbstractThe balance of activity and selectivity in liquid alkane oxidation is challenging for the design of supported Fe catalysts. When Fe species leach to the solvent, uncontrolled free radical chain reactions happen. Herein, isolated Fe(3+) species were constructed by forming a strong Fe−O−Si bond for the selective oxidation of cyclohexane to cyclohexanone by H2O2. Compared to the supported FeOx clusters, the strong Fe−O−Si bond between isolated Fe(3+) species and SiO2 prevents the leaching of Fe in strong oxidation (H2O2) reaction conditions and dominates the non‐free radical mechanism. The turnover frequency over 10FeOx/SBA‐15 reached 15.2 h−1, higher than for reported Fe‐based catalysts. High selectivity of cyclohexanone is maintained at different conversions. Moreover, the (SiO)xFe3+(OH)3‐x−OOH active species were detected by Raman and FTIR and are generated from the oxidation of isolated Fe species. The strong Fe−O−Si bond and non‐free‐radical mechanism by (SiO)xFe3+(OH)3‐x−OOH active species induce high activity and selectivity for the oxidation of many other alkanes.

Biomimetic Inorganic Nanovectors as Tumor-Targeting Theranostic Platform against Triple-Negative Breast Cancer.

Mesoporous silicon nanoparticles (PSi NPs) are promising platforms of nanomedicine because of their good compatibility, high payload capacities of anticancer drugs, and easy chemical modification. Here, PSi surfaces were functionalized with bisphosphonates (BP) for radiolabeling, loaded with doxorubicin (DOX) for chemotherapy, and the NPs were coated with cancer cell membrane (CCm) for homotypic cancer targeting. To enhance the CCm coating, the NP surfaces were covered with polyethylene glycol prior to the CCm coating. The effects of the BP amount and pH conditions on the radiolabeling efficacy were studied. The maximum BP was (2.27 wt%) on the PSi surfaces, and higher radiochemical yields were obtained for 99mTc (97% ± 2%) and 68Ga (94.6% ± 0.2%) under optimized pH conditions (pH = 5). The biomimetic NPs exhibited a good radiochemical and colloidal stability in phosphate-buffered saline and cell medium. In vitro studies demonstrated that the biomimetic NPs exhibited an enhanced cellular uptake and increased delivery of DOX to cancer cells, resulting in better chemotherapy than free DOX or pure NPs. Altogether, these findings indicate the potential of the developed platform for cancer treatment and diagnosis.

Mesoporous silicon based nano-particles for photothermal and H2O2-elevation dually-augmented chemodynamic therapy

Chemodynamic therapy (CDT) has gained significant attention due to its high tumor selectivity and minimal damage to normal tissues. However, to achieve optimal therapeutic outcomes, it is crucial to enhance the generation rate and amount of hydroxyl radicals (·OH) as they have a short lifespan. In this study, we developed hyaluronic acid-coated supramolecular nanoparticles (NPs) using β-cyclodextrin-modified hyaluronic acid (HA-CD) and ferrocene-modified mesoporous silica nanoparticles (FMSN). L-ascorbyl palmitate (PA), a prooxidant, and photosensitizers IR825 were loaded into the NPs to create NPs@PA&IR825. Through active targeted cellular internalization, PA reacts with specific proteins, thereby increasing the production of hydrogen peroxide (H2O2). The elevated H2O2 levels facilitate the generation of more ·OH through the Fenton reaction, promoting apoptosis in cancer cells. Additionally, near-infrared (NIR) activation induces hyperthermia, further enhancing the levels of ·OH. Therefore, the combination of up-regulated H2O2 and hyperthermia properties in NPs@PA&IR825 is expected to enhance the effectiveness of CDT. The excellent therapeutic performance of NPs@PA&IR825 has been demonstrated both in vitro and in vivo. This innovative approach holds promise for improving CDT efficacy by synergistically enhancing H2O2 levels and leveraging hyperthermia-induced ·OH generation.

A double network hydrogel dressing enhanced by catechin-loaded mesoporous silica for accelerating wound repair in conjunction with red-light therapy

The process of healing wounds is an intricate mechanism that the human body undergoes. However, the production of hydrogel dressings is expensive and involves a complicated manufacturing procedure. Furthermore, most wound dressings lack bioactive components, limiting their ability to actively promote wound healing. To address this issue, we have developed an adhesive hydrogel dressing for wound repair that possesses antibacterial, anti-inflammatory and antioxidant capabilities. The dressing is composed of polyethylene glycol diacrylate (PEGDA), chitosan (CS), and catechin-loaded mesoporous silicon dioxide (CMSN). The hydrogel dressing adheres tightly to tissues through topological adhesion of CS macromolecules. At the same time, CMSN slowly releases the active substance, catechin, at the wound site. Moreover, the intermolecular interactions and hydrogen bonding between CMSN and PEGDA/CS hydrogels enhance the mechanical stability of the dressing. This allows for effective closure and repair of wounds, even in areas with frequent movement. Additionally, red-light therapy can be employed to further promote wound healing. It works by enhancing blood circulation, improving wound oxygenation, and stimulating collagen synthesis. When combined with the biocompatible and adhesive hydrogel dressing, it offers a promising approach for the rapid repair of wounds in motorial wounded areas.

Mesoporous SiO2 anode armour for lithium oxygen battery

We are reporting a new lithium (Li) anode protective strategy using mesoporous silicon dioxide (mSiO2) to extend the operation lifetime for Li oxygen batteries (LOBs). The fabrication method is simple and easy for mass production. The mSiO2 protective layer inhibits the growth of Li dendrites and prevents the intrinsic Li corrosion phenomenon that occurs in all Li-metal-based batteries during charge/discharge cycles, the porous structure of nanoparticles within the mSiO2 also actively created parallel pathways for Li+ transport thus enhancing the mass transfer. Propylene carbonate/Li with a 100 μL drop amount of mSiO2 protective layer (mPL100) showed excellent per-formance in the Li||Li battery charge/discharge cycle test, withstanding 2,276 h of continuous operation, almost 16 times longer than the battery without the protective layer, and the LOB charge/discharge cycle test with the mSiO2 protective layer reached 382 cycles, another significant increase of 6.2 times over the unprotected battery, the full discharge capacity also reached 56,902 mAh/g that is nearly 19 times higher than the unprotected cell. Because the mSiO2 made Li+ flux more homogeneous meanwhile promoting the uniform distribution of positive electrode products and accelerating their decomposition, thus the overpotential is reduced. This layer also blocked any H2O and peroxide molecules which attack the Li anode, therefore the retention of Li has been kept at a satisfactory level.

Electron microscopy approach to the wetting dynamics of single organosilanized mesopores

Columnar mesoporous silicon (PSi) with hydrophobic vs. hydrophilic chemistries was chosen as a model for the local (pore-by-pore) study of water-pore interactions. Tomographic reconstructions provided a 3D view of the ramified pore structure. An in situ study of PSi wetting was conducted for categorized pore diameters by environmental scanning TEM. An appropriate setting of the contrast allows for the normalization of the gray scale in the images as a function of relative humidity (RH). This allows constructing an isotherm for each single pore and a subsequent averaging provides an isotherm for each pore size range. The isotherms systematically point to an initial adsorption through the formation of water adlayers, followed by a capillary filling process at higher RH. The local isotherms correlate with (global) gravimetric determination of wetting. Our results point at the validation of a technique for the study of aging and stability of single-pore nanoscale devices.

Comparative Study of SERS-Spectra of NQ21 Peptide on Silver Particles and in Gold-Coated "Nanovoids".

The NQ21 peptide has relatively recently attracted attention in the biomedical sphere due to its prospects for facilitating the engineering of the HIV1 vaccine and ELISA test. Today, there is still a need for a reliable and fast methodology that reveals the secondary structure of this analyte at the low concentrations conventionally used in vaccines and immunological assays. The present research determined the differences between the surface-enhanced Raman scattering (SERS) spectra of NQ21 peptide molecules adsorbed on solid SERS-active substrates depending on their geometry and composition. The ultimate goal of our research was to propose an algorithm and SERS-active material for structural analysis of peptides. Phosphate buffer solutions of the 30 µg/mL NQ21 peptide at different pH levels were used for the SERS measurements, with silver particles on mesoporous silicon and gold-coated "nanovoids" in macroporous silicon. The SERS analysis of the NQ21 peptide was carried out by collecting the SERS spectra maps. The map assessment with an originally developed algorithm resulted in defining the effect of the substrate on the secondary structure of the analyte molecules. Silver particles are recommended for peptide detection if it is not urgent to precisely reveal all the characteristic bands, because they provide greater enhancement but are accompanied by analyte destruction. If the goal is to carefully study the secondary structure and composition of the peptide, it is better to use SERS-active gold-coated "nanovoids". Objective results can be obtained by collecting at least three 15 × 15 maps of the SERS spectra of a given peptide on substrates from different batches.

Bioengineered "Molecular Glue"-Mediated Tumor-Specific Cascade Nanoreactors with Self-Destruction Ability for Enhanced Precise Starvation/Chemosynergistic Tumor Therapy.

The ordered and directed functionalization of targeting elements on the surface of nanomaterials for precise tumor therapy remains a challenge. To address the above problem, herein, we adopted a materials-based synthetic biotechnology strategy to fabricate a bioengineered fusion protein of materials-binding peptides and targeting elements, which can serve as a "molecular glue" to achieve a directional and organized assembly of targeting biological macromolecules on the surface of nanocarriers. The hypoxia microenvironment of solid tumors inspired the rapid development of starvation/chemosynergistic therapy; however, the unsatisfied spatiotemporal specific performance hindered its further development in precise tumor therapy. As a proof of concept, a bioengineered fusion protein containing a dendritic mesoporous silicon (DMSN)-binding peptide, and a tumor-targeted and acidity-decomposable ferritin heavy chain 1 (FTH1), was constructed by fusion expression and further assembled on the surface of DMSN companying with the insertion of hypoxia-activated prodrug tirapazamine (TPZ) and glucose oxidase (GOX) to establish a nanoreactor for precise starvation/chemosynergistic tumor therapy. In this context, the as-prepared therapeutic nanoreactors revealed obvious tumor-specific accumulation and an endocytosis effect. Next, the acidic tumor microenvironment triggered the structural collapse of FTH1 and the subsequent release of GOX and TPZ, in which GOX-mediated catalysis cut off the nutrition supply to realize starvation therapy based on the consumption of endogenous glucose and further provided an exacerbated hypoxia environment for TPZ in situ activation to initiate tumor chemotherapy. More significantly, the presence of "molecular glue" elevated the tumor-targeting capacity of nanoreactors and further enhanced the starvation/chemosynergistic therapeutic effect remarkably, suggesting that such a strategy provided a solution for the functionality of nanomaterials and facilitated the design of novel targeting nanomedicines. Overall, this study highlights materials-binding peptides as a new type of "molecular glue" and opens new avenues for designing and exploring active biological materials for biological functions and applications.

The mechanism and design strategy of metal-organic frameworks in drug delivery

In the field of drug transport, the traditional drugs used for drug delivery are organic, inorganic, and complex. The organic polymer system and liposome system can have good biocompatibility, but the porosity of the polymer cannot be determined, and the medicine cannot be given a controlled release. In contrast, inorganic materials such as microporous zeolite and mesoporous silicon can achieve controlled drug release due to their definite relative porosity, but their drug-loading capacity and poor biocompatibility cannot be widely used for drug delivery. The materials of the new MOFs can synthesize the advantages of the two, with controlled drug release, biocompatibility, and good flexibility, that is, the performance of targeted drug delivery. This paper focuses on the mechanism of MOFs in drug transport and the related applications of MOFs in transporting small molecules, macromolecular drugs, and the surface modification methods of MOFs. The present paper concludes that MOFs can be widely used to transport macromolecules and small-molecule drugs and that drug targeting can be improved by surface modification. This paper hopes to provide suggestions and guidance for designing future MOF materials for DDS, to promote the application efficiency of nanomaterials in relevant aspects, and to achieve efficient, highly selective and highly stable drug delivery.

Hierarchically Released Liquid Metal Nanoparticles for Mild Photothermal Therapy/Chemotherapy of Breast Cancer Bone Metastases via Remodeling Tumor Stromal Microenvironment.

Currently, the treatment strategy for bone metastasis is mainly to inhibit the growth of tumor cells and the activity of osteoclasts, while ignoring the influence of the tumor stromal microenvironment (TSM) on the progression of bone metastasis. Herein, a dual-target liquid metal (LM)-based drug delivery system (DDS) with favorable photothermal performance is designed to spatially program the delivery of multiple therapeutic agents to enhance the treatment of bone metastasis through TSM remodeling. Briefly, mesoporous silicon-coated LM is integrated into zeolitic imidazolate framework-8 (ZIF-8) with both bone-seeking and tumor-targeting capacities. Curcumin (Cur), a tumor microenvironment modulator, is encapsulated into ZIF-8, and doxorubicin (DOX) is enclosed inside mesoporous silicon. Specific accumulation of the LM-based DDS in bone metastases first relieves the tumor stroma by releasing Cur in response to the acidic tumor microenvironment and then releases DOX deep into the tumor under near-infrared light irradiation. The combined strategy of the LM-based DDS and mild photothermal therapy has been shown to effectively restrain cross-talk between osteoclasts and tumor cells by inhibiting the secretion of transforming growth factor-β, degrading extracellular matrix components, and increasing infiltration of CD4+ and CD8+ T cells, which provides a promising strategy for the treatment of bone metastases.