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1.
Small ; : e2101332, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34405525

RESUMO

Inorganic nanomedicine has attracted increasing attentions in biomedical sciences due to their excellent biocompatibility and tunable, versatile functionality. However, the relatively poor accumulation and retention of these nanomedicines in targeted tissues have often hindered their clinical translation. Herein, highly efficient, targeted delivery, and in situ aggregation of ferrocene (Fc)-capped Au nanoparticles (NPs) are reported to cucurbit[7]uril (CB[7])-capped Fe3 O4 NPs (as an artificial target) that are magnetically deposited into the tumor, driven by strong, multipoint CB[7]-Fc host-guest interactions (here defined as "supramolecular tropism" for the first time), leading to high tumor accumulation and retention of these NPs. The in vitro and in vivo studies demonstrate the precisely controlled, specific accumulation, and retention of Au NPs in the tumor cells and tissue via supramolecular tropism and in situ aggregation, which afford locally enhanced CT imaging of cancer and enable tumor-specific photothermal therapy attributed to the plasmonic coupling effects between adjacent Au NPs within the supramolecular aggregations. This work provides a novel concept of supramolecular tropism, which may drive targeted delivery and enable specific accumulation, retention, and activation of nanomedicine for improved bioimaging and therapy of cancer.

2.
Analyst ; 146(17): 5357-5361, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34333580

RESUMO

Nitrogen doped carbon dots (N-CDs) were synthesized by a one-step hydrothermal method with dopamine and ethylenediamine. The as-prepared N-CDs were characterized via transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), fluorescence spectrophotometer, UV-Vis spectrophotometry and Fourier transform infrared spectroscopy (FTIR). The average particle dimension of the as-prepared N-CDs was 2.68 nm, and the best excitation and emission wavelengths were 405 nm and 535 nm, separately. N-CDs exhibits excellent selectivity and sensitivity to detect the curcumin (Cur), attaining a wider linear range of 97.5 nM-67.9 µM and a limit of detection (LOD) of as low as 94 nM. Interestingly, N-CDs can also give responsive signals of a visible colour change (yellow to red). Moreover, a novel fluorescent/colorimetric dual-mode method has been successfully employed for the determination of Cur in real samples with good recoveries (94%-110%) and precision (RSD = 0.3-2.9%).


Assuntos
Curcumina , Pontos Quânticos , Carbono , Colorimetria , Corantes Fluorescentes , Nitrogênio , Espectrometria de Fluorescência
3.
Virus Res ; 303: 198502, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34252490

RESUMO

Enterovirus A71 (EV-A71) is an important emerging virus posing a threat to children under five years old. Circular RNAs (circRNAs), a novel class of endogenous RNAs, have been recognized to play important roles in the onset and development of viral diseases. However, it has not been determined which specific circRNAs are involved in the pathological mechanisms of EV-A71 infection. In this study, RNA-sequencing (RNA-seq) was conducted to characterize differentially expressed circRNAs during the process of EV-A71 infection. Overall, 8726, 10405 and 4710 circRNAs were detected in the control, EV-A71-12 h and EV-A71-24 h groups, respectively, of which 1851 and 951 circRNAs were differentially expressed in the EV-A71-12 h and EV-A71-24 h groups versus the control group. The overlapping circRNAs in the EV-A71-infected groups were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, which further demonstrated that the host genes of these circRNAs were principally implicated in activities associated with the progression of viral infection, such as immune system process, Wnt signaling pathway, etc. Additionally, qRT-PCR detection showed that six selected circRNAs were identical to the sequencing data. To excavate the key circRNAs in EV-A71 infection, we comprehensively evaluated and integrated the relationship of circRNA/miRNA/mRNA, and eventually screened 2 key circRNA regulatory axes, namely hsa_circ_0017115/hsa-miR-150-5p/EGR1 and hsa_circ_0005060/hsa-miR-4685-5p/MMP2. In summary, our findings not only provide the first comprehensive expression and functional profile of circRNAs in response to EV-A71 infection, but also offer a novel direction to elucidate the molecular mechanism underlying viral pathogenesis and the cellular immune response in host-EV-A71 interactions.

4.
Commun Biol ; 4(1): 803, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34211094

RESUMO

Polyamine detection and depletion have been extensively investigated for cancer prevention and treatment. However, the therapeutic efficacy is far from satisfactory, mainly due to a polyamine compensation mechanism from the systemic circulation in the tumor environment. Herein, we explore a new solution for improving polyamine detection as well as a possible consumption therapy based on a new photosensitizer that can efficiently consume polyamines via an irreversible chemical reaction. The new photosensitizer is pyrrolopyrroleaza-BODIPY pyridinium salt (PPAB-PyS) nanoparticles that can react with the over-expressed polyamine in cancer cells and produce two photosensitizers with enhanced phototoxicity on cancer destruction. Meanwhile, PPAB-PyS nanoparticles provide a simultaneous ratiometric fluorescence imaging of intracellular polyamine. This combination polyamine consumption with a chemical reaction provides a new modality to enable polyamine detection along with photodynamic therapy as well as a putative depletion of polyamines for cancer treatment and prevention.


Assuntos
Poliaminas Biogênicas/análise , Nanopartículas/química , Neoplasias/tratamento farmacológico , Fotoquimioterapia/métodos , Poliaminas Biogênicas/química , Linhagem Celular Tumoral , Humanos , Neoplasias/química , Neoplasias/prevenção & controle , Imagem Óptica
5.
Small ; 17(34): e2102286, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34258871

RESUMO

Gas therapy has emerged as a new therapeutic strategy in combating cancer owing to its high therapeutic efficacy and biosafety. However, the clinical translation of gas therapy remains challenging due to the rapid diffusion and limited tissue penetration of therapeutic gases. Herein, a self-propelled, asymmetrical Au@MnO2 nanomotor for efficient delivery of therapeutic gas to deep-seated cancer tissue for enhanced efficacy of gas therapy, is reported. The Au@MnO2 nanoparticles (NPs) catalyze endogenous H2 O2 into O2 that propels NPs into deep solid tumors, where SO2 prodrug is released from the hollow NPs owing to the degradation of MnO2 shells. Fluorescein isothiocyanate (FITC) is conjugated onto the surface of Au via caspase-3 responsive peptide (DEVD) and the therapeutic process of gas therapy can be optically self-reported by the fluorescence of FITC that is turned on in the presence of overexpressed caspase-3 as an apoptosis indicator. Au@MnO2 nanomotors show self-reported therapeutic efficacy and high biocompatibility both in vitro and in vivo, offering important new insights to the design and development of novel nanomotors for efficient payload delivery into deep tumor tissue and in situ monitoring of the therapeutic process.

6.
Talanta ; 233: 122593, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34215082

RESUMO

The latent fingerprints (LFPs) at the crime scene are unique and stable, which are considered as an important clue in criminal justice and forensic identification. Herein, a butterfly-shaped molecule DPTS with solid fluorescence plus excited-state intramolecular proton transfer (ESIPT) properties was used to develop for enhancing the visualization of the LFPs. Considering the solid fluorescence of DPTS, the color and efficiency of DPTS with a large Stokes shift (216 nm) can be tuned by changing the morphology of its aggregates, and gradually red-shifted (green-yellow-red) with increasing water content. Furthermore, its effectiveness for the detection of LFPs was demonstrated on various different substrates including paper box, tinfoil and weighting paper. The emissive fingerprint of DPTS obtained gave good fluorescence images with high contrast and resolution such as the core, delta, bifurcation, ridge termination, independent ridge and pores. Caging of the phenol donor of DPTS with a sensitive biomarker group provided DPTS-ONOO-, which had high sensitive with detection limit of 5 nM and the quantification limit of 21 nM toward ONOO-. Modularly derived DPTS-ONOO- was synthesized and demonstrated specific fluorescence imaging of exogenous and endogenous peroxynitrite (ONOO-) in living macrophage cells.


Assuntos
Corantes Fluorescentes , Prótons , Ácido Peroxinitroso , Fenol , Fenóis
7.
Acta Biomater ; 131: 483-492, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34265471

RESUMO

Photodynamic therapy (PDT), where a photosensitizer (under light irradiation) converts molecular oxygen to singlet oxygen to elicit programmed cell death, is a promising cancer treatment modality with a high temporal and spatial resolution. However, only limited cancer treatment efficacy has been achieved in clinical PDT due to the hypoxic conditions of solid tumor microenvironment that limits the generation of singlet oxygen, and PDT process often leads to even more hypoxic microenvironment due to the consumption of oxygens during therapy. Herein, we designed novel supramolecular micelles to co-deliver photosensitizer and hypoxia-responsive prodrug to improve the overall therapeutic efficacy. The supramolecular micelles (CPC) were derived from a polyethylene glycol (PEG) system dually tagged with hydrophilic cucurbit[7]uril (CB[7]) and hydrophobic Chlorin e6 (Ce6), respectively on each end, for synergistic antitumor therapy via PDT of Ce6 and chemotherapy of a hypoxia-responsive prodrug, banoxantrone (AQ4N), loaded into the cavity of CB[7]. In addition, CPC was further modularly functionalized by folate (FA) via strong host-guest interaction between folate-amantadine (FA-ADA) and CB[7] to produce a novel nanoplatform, AQ4N@CPC-FA, for targeted delivery. AQ4N@CPC-FA exhibited enhanced cellular uptake, negligible cytotoxicity and good biocompatibility, and improved intracellular reactive oxygen species (ROS) generation efficiency. More importantly, in vivo evaluation of AQ4N@CPC-FA revealed a synergistic antitumor efficacy between PDT of Ce6 and hypoxia-activated chemotherapy of AQ4N (that can be converted to chemotherapeutic AQ4 for tumor chemotherapy in response to the strengthened hypoxic tumor microenvironment during PDT treatment). This study not only provides a new nanoplatform for synergistic photodynamic-chemotherapeutic treatment, but also offers important new insights to design and development of multifunctional supramolecular drug delivery system. STATEMENT OF SIGNIFICANCE: Photodynamic therapy (PDT) has exhibited a variety of advantages for cancer phototherapy as compared to traditional chemotherapy. However, the unsatisfactory therapeutic efficacy by PDT alone as a result of the enhanced tumor hypoxia during PDT has limited its clinical application. Herein, we designed multifunctional supramolecular micelles to co-deliver photosensitizer and hypoxia-responsive prodrug to improve the overall therapeutic efficacy. The supramolecular micelles are biocompatible and possess strong red absorption, controlled drug release profile, and ultimately enhanced therapeutic outcome via PDT-chemotherapy. This study not only provides a new nanoplatform for synergistic photodynamic-chemotherapeutic treatment of cancer, but also offers important new insights to design and development of multifunctional supramolecular drug delivery tool for multi-modality cancer therapy.


Assuntos
Antineoplásicos , Fotoquimioterapia , Linhagem Celular Tumoral , Humanos , Hipóxia , Micelas , Fármacos Fotossensibilizantes/farmacologia , Medicina de Precisão
8.
Biomaterials ; 275: 120822, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34062419

RESUMO

The hypoxic tumor microenvironment (TME) and non-specific distribution of sonosensitizers are two major obstacles that limit practical applications of sonodynamic therapy (SDT) in combating tumors. Here we report a hypoxia-responsive nanovesicle (hMVs) as delivery vehicles of a sonosensitizer to enhance the efficacy of SDT via specific payload release and local oxygenation in the tumor. The nanovesicles are composed of densely packed manganese ferrite nanoparticles (MFNs) embedded in hypoxia-responsive amphiphilic polymer membranes. With δ-aminolevulinic acid (ALA) loaded in the hollow cavities, the hMVs could rapidly dissociate into discrete nanoparticles in the hypoxic TME to release the payload and induce the generation of reactive oxygen species (ROS) under ultrasound (US) radiation. Meanwhile, the released MFNs could catalytically generate O2 to overcome the hypoxic TME and thus enhance the efficacy of SDT. After treatment, the dissociated MFNs could be readily excreted from the body via renal clearance to reduce long term toxicity. In vitro and in vivo experiments displayed effective tumor inhibition via hMVs-mediated SDT, indicating the great potential of this unique nanoplatform in effective SDT by generating sufficient ROS in deep-seated hypoxic tumors that are not readily accessible by conventional photodynamic therapy.


Assuntos
Hipóxia , Nanopartículas , Linhagem Celular Tumoral , Humanos , Espécies Reativas de Oxigênio , Microambiente Tumoral
9.
Small ; : e2101139, 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34114343

RESUMO

The precise accumulation and extended retention of nanomedicines in the tumor tissue has been highly desired for cancer therapy. Here a novel supramolecular-peptide derived nanodrug (SPN) that can be transformed to microfibers in response to intracellular polyamine in cancer cells for significantly enhanced tumor specific accumulation and retention is developed. The supramolecular-peptide is constructed via the non-covalent interactions between cucurbit[7]uril (CB[7]) and Phe on Phe-Phe-Val-Leu-Lys-camptothecin conjugates (FFVLK-CPT, PC). The resultant amphiphilic supramolecular complex subsequently self-assembles into nanoparticles with a hydrodynamic diameter of 164.2 ± 3.7 nm. Upon internalization into spermine-overexpressed cancer cells, the CB[7]-Phe host-guest pairs can be competitively dissociated by spermine and can release free PC, which immediately form ß-sheet structures and subsequently reorganize into microfibers, leading to dramatically improved accumulation, retention, and sustained release of CPT in tumor cells for highly effective cancer therapy. Accordingly, this SPN exhibit rather low toxicity against non-cancerous cells due to the morphological stability and fast exocytosis of the nanodrugs in those cells without abundant spermine. This study reports the first supramolecular peptide capable of polyamine-responsive "nanoparticle-to-microfiber" transformation for specific tumor therapy with minimal side effects. This work also offers novel insights to the design and development of stimuli-responsive nanomaterials as precision medicine.

10.
Angew Chem Int Ed Engl ; 60(32): 17570-17578, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34041833

RESUMO

The clinical application of chemodynamic therapy is impeded by the insufficient intracellular H2 O2 level in tumor tissues. Herein, we developed a supramolecular nanoparticle via a simple one-step supramolecular polymerization-induced self-assembly process using platinum (IV) complex-modified ß-cyclodextrin-ferrocene conjugates as supramolecular monomers. The supramolecular nanoparticles could dissociate rapidly upon exposure to endogenous H2 O2 in the tumor and release hydroxyl radicals as well as platinum (IV) prodrugs in situ, which is reduced into cisplatin to significantly promote the generation of H2 O2 in the tumor tissue. Thus, the supramolecular nanomedicine overcomes the limitation of conventional chemodynamic therapy via the self-augmented cascade radical generation and drug release. In addition, dissociated supramolecular nanoparticles could be readily excreted from the body via renal clearance to effectively avoid systemic toxicity and ensure long term biocompatibility of the nanomedicine. This work may provide new insights on the design and development of novel supramolecular nanoassemblies for cascade chemo/chemodynamic therapy.

11.
Virol Sin ; 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34037947

RESUMO

The emergence and re-emergence of RNA virus outbreaks highlight the urgent need for the development of broad-spectrum antivirals. Polyamines are positively-charged small molecules required for the infectivity of a wide range of RNA viruses, therefore may become good antiviral targets. Cucurbit[7]uril (CB[7]), a synthetic macrocyclic molecule, which can bind with amine-based organic compounds with high affinity, has been shown to regulate bioactive molecules through competitive binding. In this study, we tested the antiviral activity of CB[7] against diverse RNA viruses, including a panel of enteroviruses (i.e. human enterovirus A71, coxsackievirus A16, coxsackievirus B3, and echovirus 11), some flaviviruses (i.e. dengue virus and Zika virus), and an alphavirus representative Semliki forest virus. CB[7] can inhibit virus replications in a variety of cell lines, and its mechanism of action is through the competitive binding with polyamines. Our findings not only for the first time provide evidence that CB[7] can be a promising broad-spectrum antiviral agent, but more importantly, offer a novel therapeutic strategy to fight against RNA viruses by supramolecular sequestration of polyamines.

12.
Nanoscale ; 13(21): 9570-9576, 2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34008688

RESUMO

Glucose starvation has emerged as a therapeutic strategy to inhibit tumor growth by regulating glucose metabolism. However, the rapid proliferation of cancer cells could induce the hypoxic tumor microenvironment (TME) which limits the therapeutic efficacy of glucose starvation by vascular isomerization. Herein, we developed a "dual-lock" supramolecular nanomedicine system for synergistic cancer therapy by integrating glucose oxidase (GOx) induced starvation and hypoxia-activated gene therapy. The host-guest interactions (that mediate nano-assembly formation) and hypoxia-activatable promoters act as two locks to keep glucose oxidase (GOx) and a therapeutic plasmid (RTP801::p53) inside supramolecular gold nanovesicles (Au NVs). Upon initial dissociation of the host-guest interactions and hence Au NVs by cancer-specific reactive oxygen species (ROS), GOx is released to consume glucose and oxygen, generate H2O2 and induce the hypoxic TME, which act as the two keys for triggering burst payload release and promoter activation, thus allowing synergistic starvation and gene therapy of cancer. This "dual-lock" supramolecular nanomedicine exhibited integrated therapeutic effects in vitro and in vivo for tumor suppression.


Assuntos
Glucose , Neoplasias , Terapia Genética , Glucose Oxidase , Humanos , Peróxido de Hidrogênio , Hipóxia , Neoplasias/terapia , Microambiente Tumoral
13.
Spectrochim Acta A Mol Biomol Spectrosc ; 256: 119751, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33819765

RESUMO

The B,N dual-doped carbon dots (B,N-CDs) for ratiometric fluorescence detection the morin were prepared from sodium tetraborate and polyethyleneimine through the single-step hydrothermal method. The B,N-CDs exhibited the optimum excitation and emission wavelength at 340 nm and 467 nm, respectively. Interestingly, the intensities of emission peak at 467 nm of B,N-CDs reduced meanwhile a new peak emerged at 560 nm with the continuous addition of morin, which revealed the ratio fluorescence characteristic between F560nm/F467nm and morin concentration with the linearity range and detection limit of 14.5-32.5 µmol/L and 0.3 µmol/L (S/N = 3), respectively. The interference of common antibiotics and remedies could be ignored when the concentration of morin was detected by the B,N-CDs, which demonstrating the outstanding selectivity. Furthermore, the proposed fluorescence method is used to detect morin in urine with recoveries are 99.8-104.5%. The results of this research indicate the feasibility and practicality of B,N-CDs as an effective fluorescent probe for the determination of morin.


Assuntos
Carbono , Pontos Quânticos , Flavonoides , Fluorescência
14.
Biomater Sci ; 9(10): 3804-3813, 2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-33881050

RESUMO

Nano-graphene oxide (NGO) has attracted increasing attention as an advanced drug delivery system. However, the current surface functionalization and drug-loading of NGO either rely on π-π stacking that is limited to aromatic molecules, or covalent conjugation that requires tedious synthesis. Herein, we developed the first cucurbit[7]uril (CB[7])-conjugated NGO (NGO-CB[7]) that allows non-covalent, modular surface functionalization and drug loading via not only traditional π-π stacking interactions between the NGO surface and functional molecules, but also strong host-guest interactions between CB[7] and guest payloads or adamantane (ADA)-tagged functional molecules, for more versatile biomedical applications. To this end, chlorin e6 (Ce6, a photosensitizer), banoxantrone dihydrochloride (AQ4N, a hypoxia-responsive prodrug) and oxaliplatin (OX, a guest of CB[7]) were co-loaded onto NGO-CB[7] via π-π stacking and host-guest interactions, respectively. Subsequently, ADA-tagged hyaluronic acid (ADA-HA) wrapped NGO-CB[7] non-covalently via CB[7]-ADA host-guest interactions to improve the physiological stability and overall biocompatibility of this supramolecular nanosystem, and to enable targeted delivery into cancer cells with CD44 receptors overexpressed. Remarkably, this supramolecular nanomedicine exhibited significant antitumor efficacy via combined photothermal/photodynamic therapy (PTT/PDT) from NGO/Ce6, as well as dual chemotherapy from OX and AQ4N (activated by PDT-enhanced hypoxia), in vitro and in vivo. This study not only offers a new supramolecular inorganic/organic hybrid nanosystem for multi-modality cancer therapy, but may also provide important new insights into noncovalent functionalization of other carbon nanomaterials and inorganic nanomaterials leading to multifunctional drug delivery systems.


Assuntos
Nanomedicina , Neoplasias , Hidrocarbonetos Aromáticos com Pontes , Imidazóis , Neoplasias/tratamento farmacológico , Óxidos
15.
Chin Chem Lett ; 2021 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-33840982

RESUMO

The wide-spreading SARS-CoV-2 virus has put the world into boiling water for more than a year, however pharmacological therapies to act effectively against coronavirus disease 2019 (COVID-19) remain elusive. Chloroquine (CQ), an antimalarial drug, was found to exhibit promising antiviral activity in vitro and in vivo at a high dosage, thus CQ was approved by the FDA for the emergency use authorization (EUA) in the fight against COVID-19 in the US, but later was revoked the EUA status due to the severe clinical toxicity. Herein, we show that supramolecular formulation of CQ by a macrocyclic host, curcurbit[7]uril (CB[7]), reduced its non-specific toxicity and improved its antiviral activity against coronavirus, working in synergy with CB[7]. CB[7] was found to form 1:1 host-guest complexes with CQ, with a binding constant of ∼104 L/mol. The CQ-CB[7] formulation decreased the cytotoxicity of CQ against Vero E6 and L-02 cell lines. In particular, the cytotoxicity of CQ (60 µmol/L) against both Vero E6 cell line and L-02 cell lines was completely inhibited in the presence of 300 µmol/L and 600 µmol/L CB[7], respectively. Furthermore, the CB[7] alone showed astonishing antiviral activity in SARS-CoV-2 infected Vero E6 cells and Mouse hepatitis virus strain A59 (MHV-A59) infected N2A cells, and synergistically improved the antiviral activity of CQ-CB[7], suggesting that CB[7]-based CQ formulation has a great potential as a safe and effective antiviral agent against SARS-CoV-2 and other coronavirus.

16.
Theranostics ; 11(3): 1513-1526, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33391548

RESUMO

Poisons always have fascinated humankind. Initially considered as deleterious or hazardous substances, the modern era has witnessed the controlled utilization of dangerous poisons in medicine and cosmetics. Simultaneously, antidotes have become crucial as reversal agents to counteract the effects of a poison, and they are also used today to positively cancel the benefits of a poison after use. Currently, the majority of poisons are composed of small molecules. This review focuses on recent developments to reverse or prevent toxic effects of poisons by encapsulation in host molecules. Cyclodextrins, cucurbiturils, acyclic cucurbituril derivatives, calixarenes, and pillararenes, have been reported to largely impact the effects of toxic compounds, thus extending the current paradigm of small molecule antidotes by adding a new family of macrocyclic compounds to the current arsenal of antidotes. Along this line of research, endogenous "harmful" species are also sequestered by one or more of these supramolecular host molecules, expanding the potential of supramolecular antidotes to diverse therapeutic areas.


Assuntos
Antídotos/farmacologia , Compostos Macrocíclicos/farmacologia , Venenos/toxicidade , Animais , Humanos , Bibliotecas de Moléculas Pequenas/farmacologia
17.
Biomater Sci ; 9(6): 2115-2123, 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33481965

RESUMO

The simultaneous near-infrared (NIR)-absorbed photodynamic therapy (PDT)/photothermal therapy (PTT) has proved to be a promising approach to increase the antitumor efficiency due to their synergistic effect. Herein, a boron dipyrromethene (BODIPY)-based photosensitizer was designed and synthesized for the enhanced synergistic NIR-absorbed PDT/PTT therapy upon NIR light irradiation. In this strategy, a three-dimensional rigid polyhedral oligomeric silsesquioxane (POSS) block was introduced into the Br-BODIPY molecule to alleviate the aggregation of the photosensitizer. The POSS hybrid BODIPY (Br-BODIPY-POSS) was further functionalized with a biocompatible amphiphilic PEG via a facile thiol-ene "click" reaction, affording Br-BODIPY-POSS-PEG2000 (BBPP). BBPP can self-assemble into nanoparticles, which maintain a competitive photothermal conversion efficiency (ηBBPP = 30.2%) with its counterpart Br-BODIPY-PEG (BBP, ηBBP = 34.5%). Significantly, BBPP exhibited a relatively higher oxygen quantum yield (ΦBBPP = 0.405) than BBP (ΦBBP = 0.175). The in vitro and in vivo experiments showed that BBPP possessed negligible dark cytotoxicity and a better phototherapeutic outcome than BBP. The proof-of-concept of the POSS hybrid photosensitizer offers guidance for the construction of single-component and PDT/PTT-balanced NIR nanoagents to promote the cancer therapeutic efficacy in the future.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Terapia Fototérmica
18.
Angew Chem Int Ed Engl ; 60(2): 618-623, 2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33128291

RESUMO

Due to the inherent resistance of bacterial biofilms to antibiotics and their serious threat to global public health, novel therapeutic agents and strategies to tackle biofilms are urgently needed. To this end, we designed and synthesized a novel guanidinium-functionalized pillar[5]arene (GP5) that exhibited high antibacterial potency against Gram-negative E. coli (BH101) and Gram-positive S. aureus (ATCC25904) strains. More importantly, GP5 effectively disrupted preformed E. coli biofilms by efficient penetration through biofilm barriers and subsequent destruction of biofilm-enclosed bacteria. Furthermore, host-guest complexation between GP5 and cefazolin sodium, a conventional antibiotic that otherwise shows negligible activity against biofilms, exhibited much enhanced, synergistic disruption activity against E. coli biofilms, thus providing a novel supramolecular platform to effectively disrupt biofilms.


Assuntos
Antibacterianos/síntese química , Calixarenos/química , Guanidina/química , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Cefazolina/farmacologia , Escherichia coli/fisiologia , Microscopia Confocal , Staphylococcus aureus/fisiologia
19.
Chemistry ; 27(19): 5890-5896, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33107654

RESUMO

Chiral α-amino acids play critical roles in the metabolic process in nearly all life forms. So far, chiral recognition of α-amino acids has mainly focused on the determination of l/d enantiomers. Herein, selection of planar chiral conformations between water-soluble pillar[5]arene WP5 and pillar[6]arene WP6 was observed due to α-side chain or ethyl ester moieties of l-α-amino acid ethyl ester hydrochlorides binding with WP5 and WP6, respectively. Therefore, α-side chain and ethyl ester moieties of l-α-amino acid ethyl ester hydrochlorides were recognized by observing the induced CD signal and its inversion. This is a rare example of being able to detect the chiral region around α-carbon of a chiral α-amino acid molecule.

20.
Angew Chem Int Ed Engl ; 60(12): 6581-6592, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33305859

RESUMO

Tumor fibrotic stroma forms complex barriers for therapeutic nanomedicine. Although nanoparticle vehicles are promising in overcoming biological barriers for drug delivery, fibrosis causes hypoxia, immunosuppression and limited immunocytes infiltration, and thus reduces antitumor efficacy of nanosystems. Herein, we report the development of cancer-associated fibroblasts (CAFs) responsive honeycomb-like nanoassemblies of carbon dots (CDs) to spatially program the delivery of multiple therapeutics for enhanced antitumor chemoimmunotherapy. Doxorubicin (DOX) and immunotherapeutic enhancer (Fe ions) are immobilized on the surface of CDs, whereas tumor microenvironment modifier (losartan, LOS) is encapsulated within the mesopores. The drugs-loaded nanoassemblies disassociate into individual CDs to release LOS to mitigate stroma and hypoxia in response to CAFs. The individual CDs carrying DOX and Fe ion efficiently penetrate deep into tumor to trigger intensified immune responses. Our in vitro and in vivo studies show that the nanoassemblies exhibit effective T cells infiltration, tumor growth inhibition and lung metastasis prevention, thereby providing a therapeutic platform for desmoplasia solid tumor.

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