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ACS Appl Mater Interfaces ; 12(16): 18342-18351, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32223204


Therapeutic efficacy of synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) is limited by complex conjugation chemistry, absorption wavelength mismatch, and inadequate biodegradability of the PDT-PTT agents. Herein, we designed biocompatible copper sulfide nanodot anchored folic acid-modified black phosphorus nanosheets (BP-CuS-FA) to overcome these limitations, consequently enhancing the therapeutic efficiency of PDT-PTT. In vitro and in vivo assays reveal good biocompatibility and commendable tumor inhibition efficacy of the BP-CuS-FA nanoconjugate because of the synergistic PTT-PDT mediated by near-infrared laser irradiation. Importantly, folic acid unit could target folate receptor overexpressed cancer cells, leading to enhanced cellular uptake of BP-CuS-FA. BP-CuS-FA also exhibits significant contrast effect for photoacoustic imaging, permitting its in vivo tracking. The photodegradable character of BP-CuS-FA is associated with better renal clearance after the antitumor therapy in vivo. The present research may facilitate further development on straightforward approaches for targeted and imaging-guided synergistic PDT-PTT of cancer.

Adv Mater ; 31(52): e1904914, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31696981


Immunogenic cell death (ICD) provides momentous theoretical principle for modern cancer immunotherapy. However, the currently available ICD inducers are still very limited and photosensitizer-based ones can hardly induce sufficient ICD to achieve satisfactory cancer immunotherapy by themselves. Herein, an organic photosensitizer (named TPE-DPA-TCyP) with a twisted molecular structure, strong aggregation-induced emission activity, and specific ability is reported for effectively inducing focused mitochondrial oxidative stress of cancer cells, which can serve as a much superior ICD inducer to the popularly used ones, including chlorin e6 (Ce6), pheophorbide A, and oxaliplatin. Furthermore, more effective in vivo ICD immunogenicity of TPE-DPA-TCyP than Ce6 is also demonstrated using a prophylactic tumor vaccination model. The underlying mechanism of the effectiveness and robustness of TPE-DPA-TCyP in inducing antitumor immunity and immune-memory effect in vivo is verified by immune cell analyses. This study thus reveals that inducing focused mitochondrial oxidative stress is a highly effective strategy to evoke abundant and large-scale ICD.

Morte Celular Imunogênica/efeitos dos fármacos , Mitocôndrias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Teoria da Densidade Funcional , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Mitocôndrias/efeitos dos fármacos , Nanopartículas/química , Neoplasias/tratamento farmacológico , Neoplasias/mortalidade , Neoplasias/patologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/química , Porfirinas/farmacologia , Porfirinas/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Taxa de Sobrevida , Raios X
Angew Chem Int Ed Engl ; 58(8): 2377-2381, 2019 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-30628146


Hypoxia plays crucial roles in many diseases and is a central target for them. Present hypoxia imaging is restricted to the covalent approach, which needs tedious synthesis. In this work, a new supramolecular host-guest approach, based on the complexation of a hypoxia-responsive macrocycle with a commercial dye, is proposed. To exemplify the strategy, a carboxyl-modified azocalix[4]arene (CAC4A) was designed that binds to rhodamine 123 (Rho123) and quenches its fluorescence. The azo groups of CAC4A were selectively reduced under hypoxia, leading to the release of Rho123 and recovery of its fluorescence. The noncovalent strategy was validated through hypoxia imaging in living cells treated with the CAC4A-Rho123 reporter pair.

Nat Chem ; 11(1): 86-93, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30455432


Heteromultivalency, which involves the simultaneous interactions of more than one type of ligand with more than one type of receptor, is ubiquitous in living systems and provides a powerful strategy to improve the binding efficiency of heterotopic species such as proteins and membranes. However, the design and development of artificial heteromultivalent receptors is still challenging owing to tedious synthesis processes and the need for precise control over the spatial arrangement of the binding sites. Here, we have designed a heteromultivalent platform by co-assembling cyclodextrin and calixarene amphiphiles, so that two orthogonal, non-covalent binding sites are distributed on the surface of the co-assembly. Binding with model peptides shows a synergistic effect of the two receptors, (hetero)multivalency and self-adaptability. The co-assembly shows promise for inhibition of the fibrillation of amyloid-ß peptides and the dissolution of amyloid-ß fibrils, substantially reducing amyloid cytotoxicity. This self-assembled heteromultivalency concept is easily amenable to other ensembles and targets, so that versatile biomedical applications can be envisaged.

Amiloide , Calixarenos , Ciclodextrinas , Peptídeos , Amiloide/química , Amiloide/metabolismo , Peptídeos beta-Amiloides , Animais , Calixarenos/química , Calixarenos/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Ciclodextrinas/química , Ciclodextrinas/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Células PC12 , Fragmentos de Peptídeos , Peptídeos/química , Peptídeos/metabolismo , Ratos
Adv Mater ; 30(26): e1801065, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29766581


Fluorescent nanoparticles (NPs) based on luminogens with aggregation-induced emission characteristic (AIEgens), namely AIE dots, have received wide attention because of their antiquenching attitude in emission and reactive oxygen species (ROS) generation when aggregated. However, few reports are available on how to control and optimize their fluorescence and ROS generation ability. Herein, it is reported that enhancing the intraparticle confined microenvironment is an effective approach to advanced AIE dots, permitting boosted cancer phototheranostics in vivo. Formulation of a "rotor-rich" and inherently charged near-infrared (NIR) AIEgen with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] and corannulene-decorated PEG affords DSPE-AIE dots and Cor-AIE dots, respectively. Compared to DSPE-AIE dots, Cor-AIE dots show 4.0-fold amplified fluorescence quantum yield and 5.4-fold enhanced ROS production, because corannulene provides intraparticle rigidity and strong interactions with the AIEgen to restrict the intramolecular rotation of AIEgen to strongly suppress the nonradiative decay and significantly facilitate the fluorescence pathway and intersystem crossing. Thus, it tremendously promotes phototheranostic efficacies in terms of NIR image-guided cancer surgery and photodynamic therapy using a peritoneal carcinomatosis-bearing mouse model. Collectively, it not only provides a novel strategy to advanced AIE dots for cancer phototheranostics, but also brings new insights into the design of superior fluorescent NPs for biomedical applications.

Hidrocarbonetos Policíclicos Aromáticos/química , Animais , Fluorescência , Camundongos , Nanopartículas , Neoplasias
J Biomed Nanotechnol ; 14(2): 240-256, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31352921


Stem cell-based therapies have emerged as promising platforms with the potential to treat serious diseases that are incurable by traditional medical approaches. To optimize the overall outcomes, it is important to understand the fate of transplanted stem cells (e.g., localization, migration, engraftment, survival, proliferation and differentiation). Fluorescent nanoparticles with good photostability and minimal perturbation of cell functions hold great promise for distinguishing transplanted stem cells from host tissues with high resolution, showing advantages over traditional histological methods. This review aims to summarize the recent advances in the use of fluorescent nanoparticles for the direct labelling of stem cells and the applications of such nanoparticles in stem cell tracking. The relevant fluorescent nanoparticles, including quantum dots, organic fluorogen-doped nanoparticles, fluorescent nanodiamonds, and upconversion nanoparticles are discussed. The advantages and limitations of the currently available fluorescent trackers are summarized, and perspectives on new research opportunities are discussed.

Rastreamento de Células , Nanopartículas , Diferenciação Celular , Medicina Regenerativa , Transplante de Células-Tronco