RESUMO
As we all know, cancer is still a disease that we are struggling against. Although the traditional treatment options are still the mainstream in clinical practice, emerging phototheranostics technologies based on photoacoustic or fluorescence imaging-guided phototherapy also provide a new exploration direction for non-invasive, low-risk and highly efficient cancer treatment. Photosensitizers are the core materials to accomplish this mission. Recently, more attention has been paid to the emerging A-D-A fused-ring photosensitizers. A-D-A fused-ring photosensitizers display strong and wide absorption spectra, high photostability and easy molecular modification. Since this type of photosensitizer was first used for tumor therapy in 2019, its application boundaries are constantly expanding. Therefore, in this feature article, from the perspective of molecular design, we focused on the development of these molecules for application in phototheranostics over the past five years. The effects of tiny structural changes on their photophysical properties are discussed in detail, which provides a way for structural optimization of the subsequent A-D-A photosensitizers.
Assuntos
Neoplasias , Fármacos Fotossensibilizantes , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/diagnóstico por imagem , Nanomedicina Teranóstica , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Estrutura Molecular , Fotoquimioterapia , Fototerapia , AnimaisRESUMO
Synchronously improving the photothermal conversion efficiency and photodynamic activity of organic small molecule photosensitizers is crucial for their further wide application in cancer treatment. Recently, the emerging A-D-A photosensitizer-based phototherapy systems have attracted great interest due to their plentiful inherent merits. Herein, we propose a design strategy for A-D-A photosensitizers with synchronously enhanced photothermal conversion and reactive oxygen species (ROS) generation efficiencies. Side chain programming is carried out to design three A-D-A photosensitizers (IDT-H, IDT-Br, IDT-I) containing hexyl, bromohexyl, and iodohexyl side chains, respectively. Theoretical calculations confirm that a bulky iodine atom could weaken the intermolecular π-π stacking and enhance spin-orbit coupling constants of IDT-I. These molecular mechanisms enable IDT-I nanoparticles (NPs) to exhibit 2.4-fold and 1.7-fold higher ROS generation efficiency than that of IDT-H NPs and IDT-Br NPs, respectively, as well as the highest photothermal conversion efficiency. Both the experimental results in vitro and in vivo verify that IDT-I NPs are perfectly qualified for the mission of photothermal and photodynamic synergistic therapy. Therefore, in this contribution, we provide a promising perspective for the design of A-D-A photosensitizers with simultaneously improved photothermal and photodynamic therapy ability.
RESUMO
Phototheranostics continues to flourish in cancer treatment. Due to the competitive relationships between these photophysical processes of fluorescence emission, photothermal conversion, and photodynamic action, it is critical to balance them through subtle photosensitizer designs. Herein, it is provided a useful guideline for constructing A-D-A photosensitizers with superior phototheranostics performance. Various cyanoacetate group-modified end groups containing ester side chains of different length are designed to construct a series of A-D-A photosensitizers (F8CA1 â¼ F8CA4) to study the structure-property relationships. It is surprising to find that the photophysical properties of A-D-A photosensitizers can be precisely regulated by these tiny structural changes. The results reveal that the increase in the steric hindrance of ester side chains has positive impacts on their photothermal conversion capabilities, but adverse impacts on the fluorescence emission and photodynamic activities. Notably, these tiny structural changes lead to their different aggregation behavior. The molecule mechanisms are detailedly explained by theoretical calculations. Finally, F8CA2 nanoparticles with more balanced photophysical properties perform well in fluorescence imaging-guided photothermal and type I&II photodynamic synergistic cancer therapy, even under hypoxic conditions. Therefore, this work provides a novel practicable construction strategy for desired A-D-A photosensitizers.
Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/química , Nanomedicina Teranóstica/métodos , Fotoquimioterapia/métodos , Fototerapia/métodos , Neoplasias/tratamento farmacológico , Nanopartículas/química , Ésteres/uso terapêuticoRESUMO
Pillararenes have columnar architectures with electron-rich cavities to endow themselves with unique host-guest complexation capability. Easy structural modifiability facilitates them to be used in many applications. Currently, pillararene based drug delivery systems (DDSs) have been developed as a powerful tool for precise diagnosis and treatment of cancer. Various functional guest molecules could be integrated with pillararenes to construct nanomaterials for cancer chemotherapy, phototherapy and chemodynamic therapy. In order to improve cancer therapy efficacy, active targeted DDSs have become particularly important. Benefiting from the good host-guest properties and structural variability of pillararenes, tumor targeting groups could be easily introduced into pillararene based DDSs to realize precise drug delivery at tumor sites. In this feature article, we provide a comprehensive summary of the present design strategy for pillararene based active targeted DDSs, which can be classified into three types namely host-guest complexation, charge reversal and targeted group modified pillararenes. Some important examples are selected to for a detailed discussion on their respective strengths and weaknesses.
RESUMO
The construction of a smart drug-delivery system based on amphiphilic pillararenes with multiple responsiveness properties has become an important way to improve the efficacy of tumor chemotherapy. Here, a new PEG-functionalized pillararene (EtP5-SS-PEG) containing disulfide and amido bonds was designed and synthesized, which has been used to construct a novel supramolecular nanocarrier through a host-guest interaction with a perylene diimide derivative (PDI-2NH4 ) and their supramolecular self-assembly. This nanocarrier showed good drug loading capability, and dual stimulus responsiveness to enzyme and GSH (glutathione). After loading of doxorubicin (DOX), the prepared nanodrugs displayed efficient DOX release and outstanding cancer theranostics ability.
Assuntos
Neoplasias , Medicina de Precisão , Humanos , Sistemas de Liberação de Medicamentos , Doxorrubicina , Neoplasias/tratamento farmacológico , Micelas , GlutationaRESUMO
Methyl-modified niobium-doped silica (Nb/SiO2) materials with various Nb/Si molar ratios (nNb) were fabricated using tetraethoxysilane and methyltriethoxysilane as the silica source and niobium pentachloride as the niobium source by the sol-gel method, and the Nb/SiO2 membranes were prepared thereof by the dip-coating process under an N2 calcining atmosphere. Their microstructures were characterized and gas permeances tested. The results showed that the niobium element existed in the formation of the Nb-O groups in the Nb/SiO2 materials. When the niobium doping content and the calcining temperature were large enough, the Nb2O5 crystals could be formed in the SiO2 frameworks. With the increase of nNb and calcination temperature, the formed particle sizes increased. The doping of Nb could enhance the H2/CO2 and H2/N2 permselectivities of SiO2 membranes. When nNb was equal to 0.08, the Nb/SiO2 membrane achieved a maximal H2 permeance of 4.83 × 10-6 mol·m-2·Pa-1·s-1 and H2/CO2 permselectivity of 15.49 at 200 °C and 0.1 MPa, which also exhibited great hydrothermal stability and thermal reproducibility.