Preparation of Triple‐Responsive Porous Silica Carriers and Carbon Quantum Dots for Photodynamic‐/Chemotherapy and Multicolor Cell Imaging

Abstract

Photosensitive carbon quantum dots (CQDs) provide a new route to treat cancer owing to their ability to produce singlet oxygen. In this paper, pH/redox/enzyme‐responsive porous silica‐based carriers with CQDs were constructed for photodynamic‐chemical combination therapy. The porous silica (pSiO2) sample comprises uniform spheres with center‐radial channels, which is favorable for drug loading and delivery. CQDs with a size of 2.5 nm were synthesized and have the excellent ability to generate singlet oxygen. After loading CQDs and drug molecules, the channels of pSiO2 carrier were blocked with hyaluronic acid (HA)/chitosan (CHI) layer. The disulfide bonds, conjugating HA to the surface of pSiO2 carrier, would achieve redox‐responsive drug release, while breaking disulfide bonds and the HA/CHI layer could endow the pSiO2 carrier enzyme/pH‐responsive drug release. The prepared pSiO2 carriers display low cytotoxicity and good biocompatibility for multicolor imaging and photodynamic‐/chemotherapy.

Recent progress in the applications of silica-based nanoparticles

“…Therefore, pH/redox/enzyme responsive SNPs carriers with carbon quantum dots were fabricated to use in photodynamicchemotherapy. 110 Another new core-interlayer-shell DOX/ZnPc co-loaded MSNs@pH-sensitive CaP@PEGylated liposome was fabricated using mesoporous silica hybrids (MSNs@CaP@PE-Gylated liposomes) and extruding DOX-loaded MSNs@CaP into ZnPc-loaded PEGylated liposomes for collaborative PDT and to improve synergetic chemo-photodynamic therapy. 111 DOXloaded MSNs-coated Au-cube-in-cubes nanocomplex (RGD-CCmMC/DOX) was constructed with RGD peptide modications as a triple mode of combinatorial therapy based on mesoporous silica for multimodal imaging and tumor-targeted triple-synergetic cancer-therapy.…”

Tumor Microenvironment-Responsive Nanomaterials as Targeted Delivery Carriers for Photodynamic Anticancer Therapy

“…Therefore, Ce6-Ns can effectively enhance the accumulation of Ce6 in tumor sites and improve the efficiency of PDT. Chen et al ( 2020 ) prepared a triplet responsive porous silica carrier (named pSiO2 -ss-HA/CHI) to load carbon quantum dots and doxorubicin for photodynamic / chemotherapy. Firstly, an amino-functional porous silica nanoparticles with central radial pores were prepared using an emulsion method, and then succinic acid and cystamine were successively grafted onto the surface of the nanoparticles via amide bonds as linkers.…”

Enzyme-Responsive Double-Locked Photodynamic Molecular Beacon for Targeted Photodynamic Anticancer Therapy

“…44−49 This approach has also been extended to nanosystems which are responsive to three stimuli. 51,52 For the examples reported so far, the acidic environment of the tumor and the overproduced glutathione (GSH), H 2 O 2 , and enzymes in cancer cells are utilized as the stimuli. To the best of our knowledge, activatable photosensitizers using two tumor-associated enzymes as stimuli have not been reported so far, though a few dual-enzyme-activated fluorescent probes have been reported.…”

“…To further enhance the tumor specificity, a number of dual stimuli-responsive photosensitizing systems have been developed, of which the PDT efficacy can be enhanced in the presence of two stimuli. − This concept was first reported by Ozlem and Akkaya, who prepared a boron dipyrromethene-based photosensitizer that was responsive toward both Na + and H + ions, functioning as a molecular AND logic gate . While most of these systems are in a nanostructured form, − the molecular counterparts are rare, and very often they can still be partially activated in the presence of one of the stimuli. − This approach has also been extended to nanosystems which are responsive to three stimuli. , For the examples reported so far, the acidic environment of the tumor and the overproduced glutathione (GSH), H 2 O 2 , and enzymes in cancer cells are utilized as the stimuli. To the best of our knowledge, activatable photosensitizers using two tumor-associated enzymes as stimuli have not been reported so far, though a few dual-enzyme-activated fluorescent probes have been reported. − We report herein such a system in a molecular form that can only be activated by the coexistence of matrix metalloproteinase-2 (MMP-2) and cathepsin B.…”