RESUMEN
The development of more effective tumor therapy remains challenging and has received widespread attention. In the past decade, there has been growing interest in synergistic tumor therapy based on supramolecular coordination complexes. Herein, we describe two triangular metallacycles (1 and 2) constructed by the formation of pyridyl boron dipyrromethene (BODIPY)-platinum coordination. Metallacycle 2 had considerable tumor penetration, as evidenced by the phenylthiol-BODIPY ligand imparting red fluorescent emission at â¼660 nm, enabling bioimaging, and transport visualization within the tumor. Based on the therapeutic efficacy of the platinum(II) acceptor and high singlet oxygen (1O2) generation ability of BODIPY, 2 was successfully incorporated into nanoparticles and applied in chemo-photodynamic tumor therapy against malignant human glioma U87 cells, showing excellent synergistic therapeutic efficacy. A half-maximal inhibitory concentration of 0.35 µM was measured for 2 against U87 cancer cells in vitro. In vivo experiments indicated that 2 displayed precise tumor targeting ability and good biocompatibility, along with strong antitumor effects. This work provides a promising approach for treating solid tumors by synergistic chemo-photodynamic therapy of supramolecular coordination complexes.
Asunto(s)
Compuestos de Boro , Neoplasias , Fotoquimioterapia , Compuestos de Boro/uso terapéutico , Línea Celular Tumoral , Complejos de Coordinación/uso terapéutico , Sinergismo Farmacológico , Humanos , Neoplasias/tratamiento farmacológico , Platino (Metal)/uso terapéutico , Porfobilinógeno/análogos & derivadosRESUMEN
Various drug delivery strategies to improve cancer therapeutic efficacy have been actively investigated. One major challenge is to improve the targeting ability. Here elaborately designed nanocarriers (NCs) named as Tf-5-ALA-PTX-NCs are demonstrated to address this problem. In this nanostructure, paclitaxel (PTX) and 5-aminolevulinic acid (5-ALA) were co-encapsulated within magnetic nanocarriers to achieve synergistic chemotherapy and photodynamic therapy, while transferrin (Tf) was conjugated with modified copolymer Pluronic P123 and embedded in the surface of the nanocarriers, which endows nanocarriers with Tf targeting and magnetic targeting to enhance the anti-tumor outcome. Results demonstrated that Tf-5-ALA-PTX-NCs significantly enhanced the targeting drug delivery to MCF-7 cells and synergistically induced apoptosis and death of MCF-7 cells in vitro and highly efficient tumor ablation in vivo. Intriguingly, Tf-5-ALA-PTX-NCs have a controllable "on/off" switch to enhance the drug release. The dual-targeted nanocarriers would be a promising versatile anti-tumor drug delivery and imaging-guided cancer chemo-photodynamic synchronization therapy strategy.
Asunto(s)
Nanopartículas , Neoplasias , Fotoquimioterapia , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos/métodos , Liberación de Fármacos , Humanos , Espectroscopía de Resonancia Magnética , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Paclitaxel , Receptores de Transferrina , TransferrinaRESUMEN
Chemo-photodynamic synergistic therapy (CPST) holds tremendous promise for treating cancers. Unfortunately, existing CPST applications suffer from complex synthetic procedures, low drug co-loading efficiency, and carrier-related toxicity. To address these issues, we have developed a supramolecular carrier-free self-sensitized nanoassemblies by co-assembling podophyllotoxin (PTOX) and chlorin e6 (Ce6) to enhance CPST efficiency against tumors. The nanoassemblies show stable co-assembly performance in simulative vivo neural environment (â¼150 nm), with high co-loading ability for PTOX (72.2 wt%) and Ce6 (27.8 wt%). In vivo, the nanoassemblies demonstrate a remarkable ability to accumulate at tumor sites by leveraging the enhanced permeability and retention (EPR) effect. The disintegration of nanoassemblies following photosensitizer bioactivation triggered by the acidic tumor environment effectively resolves the challenge of aggregation-caused quenching (ACQ) effect. Upon exposure to external light stimulation, the disintegrated nanoassemblies not only illuminate cancer cells synergistically but also exert a more potent antitumor effect when compared with PTOX and Ce6 administered alone. This self-sensitized strategy represents a significant step forward in CPST, offering a unique co-delivery paradigm for clinic cancer treatment.
Asunto(s)
Clorofilidas , Nanopartículas , Fotoquimioterapia , Fármacos Fotosensibilizantes , Podofilotoxina , Porfirinas , Fotoquimioterapia/métodos , Porfirinas/administración & dosificación , Porfirinas/química , Animales , Fármacos Fotosensibilizantes/administración & dosificación , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacocinética , Humanos , Línea Celular Tumoral , Nanopartículas/química , Podofilotoxina/administración & dosificación , Podofilotoxina/química , Neoplasias/tratamiento farmacológico , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , FemeninoRESUMEN
It is a still tough task to precisely target cancer cells and efficiently improve the therapeutic efficacy of various therapies at the same time. Here, dual-template imprinting polymer nanoparticles (MIPs) with a core-shell structure were prepared, in which fluorescent silica nanoparticles (FSiO2) were the core and the imprinted polymer layers were the outermost shell. The imprinted layer was designed and constructed via free-radical precipitation approach on the surface of FSiO2, which simultaneously encapsulated gadolinium-doped silicon quantum dots and photosensitizers (Ce6). During the polymerization process, two template molecules were introduced into the mixtures, one was the epitope of CD59 protein (YNCPNPTADCK), which was overexpressed on the surface of a great deal of the solid cancers, and the other was antitumor agent doxorubicin (DOX) to be used for chemotherapy. Furthermore, the embedded Ce6 could generate toxic 1O2 under 655 nm laser irradiation to kill cancer cells, combining with the loaded-DOX to obtain a synergistic cancer therapy. Moreover, owing to the introduction of gadolinium-doped silicon quantum dots, Ce6, and DOX, the MIPs were endowed with targeted fluorescence imaging (FI) and MR imaging (MRI). In vitro and in vivo experiments had been conducted to demonstrate the excellent targeting ability and desirable treatment effect with negligible toxicity to healthy tissues and organs. As a consequence, the designed MIPs can promote the development of targeted recognition against biomarkers and precise treatment guided with cell imaging tools.
Asunto(s)
Portadores de Fármacos/química , Epítopos/química , Impresión Molecular/métodos , Nanopartículas/química , Fotoquimioterapia/métodos , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Supervivencia Celular/efectos de los fármacos , Sinergismo Farmacológico , Humanos , Células MCF-7 , Ratones , Ratones Endogámicos BALB C , Imagen Óptica/métodos , Polímeros/químicaRESUMEN
We herein present a three-in-one nanoplatform (named Fu/LD@RuCD) for dual-drug delivery, two-photon imaging, and chemo-photodynamic synergistic therapy, enabled by simple self-assembly between adamantine-functionalized ruthenium complexes ([Ru(phen-ad)3](PF6)2, Ru) and natural cyclodextrin (ß-CD) monomers. By host-guest chemistry, nanocarrier RuCD 70-90 nm in diameter is fabricated through a very simple mixing step in water at room temperature, in which the octahedral configuration of Ru complex provides a rigid skeleton and the hydrogen bonding of secondary hydroxyl groups formed between two adjacent ß-CD monomers displays a bridging role allowing for three-dimensional architectures. The dual-drug-loaded nanoparticle Fu/LD@RuCD (Fu: 5-fluorouracil; LD: lonidamine) effectively penetrates into cancer cells in 8 h and selectively accumulates in lysosomes, in which dual-drug release is promoted by the mildly acidic environment. Under visible light irradiation, nanocarrier RuCD exhibits excellent photodynamic therapy capability by producing sufficient reactive oxygen species and damaging lysosomes, accordingly 5-fluorouracil and lonidamine can escape from lysosomes and reach their sites of action, resulting in mitochondria dysfunction and cancer cell apoptosis. Simultaneously, the excellent photophysical properties of the nanocarrier enable the facile track of drug delivery under one-photon and two-photon excitation. Moreover, in vivo anticancer investigations show that Fu/LD@RuCD can effectively inhibit the tumor growth without systemic side effects by chemo-photodynamic synergistic therapy, and the therapeutic effect is better than the free anticancer drugs and the sole therapeutic modality.