Spacer Intercalated Disassembly and Photodynamic Activity of Zinc Phthalocyanine Inside Nanochannels of Mesoporous Silica Nanoparticles

Hydrophobic photosensitizer zinc­(II) phthalocyanine (ZnPc) was loaded into adamantane (Ad) modified nanochannels of mesoporous silica nanoparticles (MSNPs). The Ad units on the surface of MSNPs were complexed with amino-substituted β-cyclodextrin to enhance the solubility of the hybrid in aqueous solution. The amino groups on β-cyclodextrin also provide functional sites for further conjugation with targeting ligands toward targeted cancer therapy. Since the intercalation of the Ad spacer isolates loaded ZnPc and prevents its aggregation inside MSNPs, ZnPc exhibits its monomeric characteristics to effectively generate cytotoxic singlet oxygen (¹O₂) upon light irradiation (675 nm) in aqueous conditions, leading to efficient photodynamic activity for successful cancer treatment in vitro. Current research presents a convenient approach to maintain the monomeric state of hydrophobic photosensitizer ZnPc by rationally utilizing multifunctional MSNPs as the carriers. The novel hybrid with targeting capability achieves active photodynamic property of monomeric ZnPc in aqueous solution under light irradiation, which may find its way for practical photodynamic therapy in the future

Targeted Delivery of 5‑Aminolevulinic Acid by Multifunctional Hollow Mesoporous Silica Nanoparticles for Photodynamic Skin Cancer Therapy

5-Aminolevulinic acid (5-ALA) is a precursor of a strong photosensitizer, protoporphyrin IX (PphIX), for photodynamic therapy (PDT). Developing appropriate delivery carriers that can assist 5-ALA in bypassing the lipophilic barrier to directly enter into cancer cells is a research focus. The improved delivery of 5-ALA is even important for skin cancer therapy through PDT process. In this work, targeting ligand folic acid (FA)-functionalized hollow mesoporous silica nanoparticles (HMSNPs) were fabricated to deliver 5-ALA for PDT against B16F10 skin cancer cells. The FA targeting ligand enabled selective endocytosis of 5-ALA loaded HMSNPs into cancer cells. PphIX formed from delivered 5-ALA exhibited high photocytotoxicity to the cancer cells in vitro

Anticancer Effect of α‑Tocopheryl Succinate Delivered by Mitochondria-Targeted Mesoporous Silica Nanoparticles

Mitochondria targeted mesoporous silica nanoparticles (MSNPs) having an average diameter of 68 nm were fabricated and then loaded with hydrophobic anticancer agent α-tocopheryl succinate (α-TOS). The property of targeting mitochondria was achieved by the surface functionalization of triphenylphosphonium (TPP) on MSNPs, since TPP is an effective mitochondria-targeting ligand. Intracellular uptake and mitochondria targeting of fabricated MSNPs were evaluated in HeLa and HepG2 cancerous cell lines as well as HEK293 normal cell line. In addition, various biological assays were conducted with the aim to investigate the effectiveness of α-TOS delivered by the functional MSNPs, including studies of cytotoxicity, mitochondria membrane potential, intracellular adenosine triphosphate (ATP) production, and apoptosis. On the basis of these experiments, high anticancer efficiency of α-TOS delivered by mitochondria targeted MSNPs was demonstrated, indicating a promising application potential of MSNP-based platform in mitochondria targeted delivery of anticancer agents

Reduction-Responsive Carbon Dots for Real-Time Ratiometric Monitoring of Anticancer Prodrug Activation in Living Cells

Anticancer prodrugs have been extensively investigated to lower toxic side effects of common chemotherapeutic agents in biomedical fields. To illustrate the activation mechanism of anticancer prodrugs, fluorescent dyes or single-emission intensity alteration-based approaches have been widely used. However, fluorescent dyes often suffer from poor photostability and chemical stability, and single-emission intensity alteration-based methods cannot avoid the influence from uncontrolled microenvironment changes in living samples. To overcome these obstacles, herein, a fluorescence resonance energy transfer (FRET)-based ratiometric approach was successfully developed for real-time monitoring of anticancer prodrug activation. Excitation-wavelength-dependent and full-color-emissive carbon dots (CDs) were used as drug nanocarriers and FRET donor, and a cisplatin­(IV) prodrug was selected as the model drug and the linker to load the Dabsyl quencher on the surface of CDs. Owing to the FRET effect, the blue fluorescence of CDs was effectively quenched by the Dabsyl unit. Under reductive conditions in solution or in living cells for the reduction of cisplatin­(IV) prodrug to Pt­(II) species, the blue fluorescence of CDs increased over time, without apparent intensity change for green or red fluorescence. Thus, the gradually enhanced intensity ratio of blue-to-green or blue-to-red fluorescence could be indicative of the real-time reduction of the cisplatin­(IV) prodrug to cytotoxic Pt­(II) species. This ratiometric method could exclude the influence from complex biological microenvironments by using green or red fluorescence of CDs as an internal reference, which provides new insights into the activation of the cisplatin­(IV) prodrug and offers a great opportunity to design safe and effective anticancer therapeutics

Dual-Responsive Carbon Dots for Tumor Extracellular Microenvironment Triggered Targeting and Enhanced Anticancer Drug Delivery

In this work, pH/redox dual-responsive carbon dots (CDs-RGD-Pt­(IV)-PEG) were fabricated for tumor extracellular microenvironment triggered targeting and enhanced anticancer drug delivery. The system consists of fluorescent carbon dots as imaging-guided drug nanocarriers, cisplatin­(IV) as prodrug, and RGD peptide as active targeting ligand, which is covered by monomethoxypolyethylene glycol (mPEG) through tumor extracellular pH (6.5–6.8) responsive benzoic-imine bond. The drug nanocarriers could be tracked by multicolor fluorescence of carbon dots. After the hydrolysis of benzoic-imine bond at the tumor extracellular pH to expose the inner targeting RGD peptide, the drug nanocarriers showed effective uptake by cancer cells through RGD-integrin α_<i>v</i>β₃ (ligand–receptor) interaction. Upon the internalization, the loaded cisplatin­(IV) prodrug was reduced to cytotoxic cisplatin in reductive cytosol of cancer cells to exhibit therapeutic effects. Confocal imaging, flow cytometry, and cell viability assays using CDs-RGD-Pt­(IV)-PEG were performed to reveal the enhanced uptake and better therapeutic efficiency to cancer cells with high integrin α_<i>v</i>β₃ expression at tumor extracellular pH than that in physiological condition. The developed CDs-RGD-Pt­(IV)-PEG offers a new strategy to provide safe and effective therapeutic agents based on carbon dots for promising cancer therapy

One-Pot Synthesis of Antitumor Agent PMX 610 by a Copper(II)-Incorporated Mesoporous Catalyst

PMX 610 ((2-(3,4-dimethoxyphenyl)-5-fluorobenzothiazole) is a benzothiazole derivative, which shows potent antitumor properties. In this study, copper­(II)-chelated pyrazole functionalized SBA-15 mesoporous silica (Cu-Py-SBA-15) as a heterogeneous green catalyst was developed for the synthesis of substituted benzothiazole derivatives including PMX 610. The preparation of pyrazole functionalized SBA-15 (Py-SBA-15) was achieved by postsynthetic modification of mesoporous silica SBA-15 with 3-aminopropyltriethoxy-silane followed by the Schiff-base condensation with 1-phenyl-3-(2′-hydroxyphenyl)-4-formyl pyrazole. The reaction of Py-SBA-15 with CuCl₂·2H₂O in absolute ethanol afforded the Cu-Py-SBA-15 catalyst. The as-synthesized catalyst was fully characterized by several techniques including powder X-ray diffraction, high-resolution transmission electron microscopy, electron paramagnetic resonance spectroscopy, X-ray photoelectron spectroscopy, ¹³C cross-polarization magic angle spinning NMR, Fourier transform infrared spectroscopy, field emission scanning electron microscopy, and N₂ adsorption/desorption measurements. A one-pot-three-component approach in aqueous medium using the Cu-Py-SBA-15 catalyst was exploited for direct synthesis of PMX 610. The novel heterogeneous green catalyst offers high catalytic recyclability without considerable loss of catalytic activity. The present synthetic strategy is valuable in the preparation of PMX 610 on account of the use of readily available and inexpensive starting materials, excellent recyclability of the catalyst, and sustainable catalytic protocol

Light-Controllable Cucurbit[7]uril-Based Molecular Shuttle

The design and construction of novel artificial molecular machines can be categorized as a currently important field of modern chemistry. In the present work, a novel photoresponsive [3]­rotaxane containing two cucurbit[7]­uril (CB[7]) rings and a dumbbell component consisting of one <i>trans</i>-azobenzene unit along with two viologen units was developed. Each viologen group was encircled by a CB[7] ring with a rapid shuttling equilibration distribution extended to the <i>trans</i>-azobenzene unit located in the middle of the dumbbell component. Upon the <i>trans</i>-to-<i>cis</i> photoisomerization of the azobenzene unit under UV light irradiation, a shuttling restriction of the CB[7] rings along the dumbbell component was observed. The equilibration distribution of the macrocycles on the dumbbell component can be recovered by the <i>cis</i>-to-<i>trans</i> photoisomerization of the azobenzene unit under visible light irradiation. Such a controllable shuttling process was fully characterized by ¹H NMR spectroscopy and was easily indicated by fluorescent changes of the [3]­rotaxane

Biocompatible Pillararene-Assembly-Based Carriers for Dual Bioimaging

Present research provides a successful example to use biocompatible pillararene-based assemblies for delivering mixed dyes in dual bioimaging. A series of tadpole-like and bola amphiphilic pillararenes <b>1</b>–<b>4</b> were synthesized by selectively employing water-soluble ethylene glycols and hydrophobic alkyl units as the starting materials. In comparison with their monomers, these amphiphilic pillararenes not only show improved biocompatibility to cells but also could form homogeneous supramolecular self-assemblies. Interestingly, different types of amphiphilic pillararene-based assemblies exhibit various performances on the delivery of dyes with different aqueous solubility. All assemblies can deliver water-soluble rhodamine B to cells, while only tadpole-like amphiphilic pillararene-based assemblies performed better on delivering hydrophobic fluorescein isothiocyanate for imaging. In addition, pillararene derivatives <b>1</b>, <b>3</b>, and <b>4</b> could complex with a viologen guest, further forming stable assemblies for bioimaging. In such cases, the assembly formed from the complex of tadpole-like amphiphile pillararene <b>1</b> with the viologen guest performed better in delivering mixed dyes. Finally, an anticancer drug, doxorubicin, was successfully delivered to cells by using the pillararene-based assemblies. The current research has determined the capacities of pillararene-based assemblies to deliver different dyes for bioimaging and paves the way for using these biocompatible carriers toward combined cancer therapy

Graphene-Based Microbots for Toxic Heavy Metal Removal and Recovery from Water

Heavy metal contamination in water is a serious risk to the public health and other life forms on earth. Current research in nanotechnology is developing new nanosystems and nanomaterials for the fast and efficient removal of pollutants and heavy metals from water. Here, we report graphene oxide-based microbots (GOx-microbots) as active self-propelled systems for the capture, transfer, and removal of a heavy metal (i.e., lead) and its subsequent recovery for recycling purposes. Microbots’ structure consists of nanosized multilayers of graphene oxide, nickel, and platinum, providing different functionalities. The outer layer of graphene oxide captures lead on the surface, and the inner layer of platinum functions as the engine decomposing hydrogen peroxide fuel for self-propulsion, while the middle layer of nickel enables external magnetic control of the microbots. Mobile GOx-microbots remove lead 10 times more efficiently than nonmotile GOx-microbots, cleaning water from 1000 ppb down to below 50 ppb in 60 min. Furthermore, after chemical detachment of lead from the surface of GOx-microbots, the microbots can be reused. Finally, we demonstrate the magnetic control of the GOx-microbots inside a microfluidic system as a proof-of-concept for automatic microbots-based system to remove and recover heavy metals

Graphene-Based Microbots for Toxic Heavy Metal Removal and Recovery from Water

Heavy metal contamination in water is a serious risk to the public health and other life forms on earth. Current research in nanotechnology is developing new nanosystems and nanomaterials for the fast and efficient removal of pollutants and heavy metals from water. Here, we report graphene oxide-based microbots (GOx-microbots) as active self-propelled systems for the capture, transfer, and removal of a heavy metal (i.e., lead) and its subsequent recovery for recycling purposes. Microbots’ structure consists of nanosized multilayers of graphene oxide, nickel, and platinum, providing different functionalities. The outer layer of graphene oxide captures lead on the surface, and the inner layer of platinum functions as the engine decomposing hydrogen peroxide fuel for self-propulsion, while the middle layer of nickel enables external magnetic control of the microbots. Mobile GOx-microbots remove lead 10 times more efficiently than nonmotile GOx-microbots, cleaning water from 1000 ppb down to below 50 ppb in 60 min. Furthermore, after chemical detachment of lead from the surface of GOx-microbots, the microbots can be reused. Finally, we demonstrate the magnetic control of the GOx-microbots inside a microfluidic system as a proof-of-concept for automatic microbots-based system to remove and recover heavy metals