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1.
Adv Mater ; : e1908109, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32022983

RESUMO

Photodynamic therapy (PDT) efficacy has been severely limited by oxygen (O2 ) deficiency in tumors and the electron-hole separation inefficiency in photosensitizers, especially the long-range diffusion of O2 toward photosensitizers during the PDT process. Herein, novel bismuth sulfide (Bi2 S3 )@bismuth (Bi) Z-scheme heterostructured nanorods (NRs) are designed to realize the spatiotemporally synchronous O2 self-supply and production of reactive oxygen species for hypoxic tumor therapy. Both narrow-bandgap Bi2 S3 and Bi components can be excited by a near-infrared laser to generate abundant electrons and holes. The Z-scheme heterostructure endows Bi2 S3 @Bi NRs with an efficient electron-hole separation ability and potent redox potentials, where the hole on the valence band of Bi2 S3 can react with water to supply O2 for the electron on the conduction band of Bi to produce reactive oxygen species. The Bi2 S3 @Bi NRs overcome the major obstacles of conventional photosensitizers during the PDT process and exhibit a promising phototherapeutic effect, supplying a new strategy for hypoxic tumor elimination.

2.
Mol Genet Genomic Med ; 8(1): e1017, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31782911

RESUMO

OBJECTIVE: To investigate the expression of long-chain noncoding growth stasis specific protein 6 antisense RNA1 (lncRNA DLX6-AS1) in nasopharyngeal carcinoma (NPC) tissues and cells, and its regulatory effect on malignant phenotypes of NPC cells. METHODS: The expressions of DLX6-AS1, miR-199a-5p, and HIF-1α mRNA in NPC issues and cells were detected by qRT-PCR. The proliferation, metastasis, and invasion of cells were monitored via MTT and transwell assay. The interactions between DLX6-AS1 and miR-199a-5p, miR-199a-5p and HIF-1α were verified by luciferase activity assay. Western blot was performed to determine the regulatory effect of DLX6-AS1 and miR-199a-5p on HIF-1α protein. RESULTS: The expression of lncRNA DLX6-AS1 was up-regulated in NPC tissues and cells. The proliferation, migration, and invasion of NPC were enhanced by overexpressed DLX6-AS1 but inhibited by DLX6-AS1 knockdown. In addition, DLX6-AS1 can be used as a kind of ceRNA to regulate miR-199a-5p and, thereby modulating the expression of HIF-1α. CONCLUSION: We found that DLX6-AS1 was a cancer-promoting lncRNA to facilitate the progression of NPC, and its underlying mechanism was suppressing miR-199a-5p expression. This study can provide novel clues for the treatment of NPC.

3.
Theranostics ; 9(19): 5577-5594, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534504

RESUMO

Rationale: Colorectal cancer (CRC) is one of the most common cancers worldwide. Ciclopirox olamine (CPX) has recently been identified to be a promising anticancer candidate; however, novel activities and detailed mechanisms remain to be uncovered. Methods: The cytotoxic potential of CPX towards CRC cells was examined in vitro and in vivo. The global gene expression pattern, ROS levels, mitochondrial function, autophagy, apoptosis, etc. were determined between control and CPX-treated CRC cells. Results: We found that CPX inhibited CRC growth by inhibiting proliferation and inducing apoptosis both in vitro and in vivo. The anti-cancer effects of CPX involved the downregulation of DJ-1, and overexpression of DJ-1 could reverse the cytotoxic effect of CPX on CRC cells. The loss of DJ-1 resulted in mitochondrial dysfunction and ROS accumulation, thus leading to CRC growth inhibition. The cytoprotective autophagy was provoked simultaneously, and blocking autophagy pharmacologically or genetically could further enhance the anti-cancer efficacy of CPX. Conclusion: Our study demonstrates that DJ-1 loss-induced ROS accumulation plays a pivotal role in CPX-mediated CRC inhibition, providing a further understanding for CRC treatment via modulating compensatory protective autophagy.

4.
ACS Appl Mater Interfaces ; 11(37): 33725-33733, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31449386

RESUMO

Wound healing is a dynamic, interactive, and complex process, including multiple stages. Although various nanomaterials are applied to accelerate the wound healing process through exhibiting antibacterial activity or promoting cell proliferation, only a single stage is promoted during the process, lowering healing efficacy. It is necessary to develop programmable nanosystems for promoting multiple wound healing stages in sequence. Herein, arginine-loaded and detachable ceria-graphene nanocomposites (ACG NCs) were designed to achieve this purpose. Ceria NPs and graphene were linked by base-cleavable N-hydroxysuccinimide ester. At inflammation stage, ACG NCs could effectively generate reactive oxygen species (ROS) and kill bacteria under white light irradiation due to their efficient electron-hole separation between ceria NPs and graphene. At proliferation stage, ceria NPs could be detached from ACG NCs and taken up by cells to scarify intracellular ROS and promote cell proliferation, while the separated graphene could act as a scaffold to promote fibroblast migration to wound site. A series of in vitro and in vivo assessments demonstrated that ACG NCs could effectively accelerate wound healing process.

5.
Nano Lett ; 19(10): 6800-6811, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31466437

RESUMO

Nitric oxide (NO) molecular messenger can reverse the multidrug resistance (MDR) effect of cancer cells through reducing P-glycoprotein (P-gp) expression, beneficial for creating a favorable microenvironment for the treatment of doxorubicin (Dox)-resistant cancer cells. Development of sophisticated nanosystems to programmably release NO and Dox becomes an efficient strategy to overcome the MDR obstacles and achieve promising therapeutic effects in Dox-resistant cancer. Herein, a NO stimulated nanosystem was designed to engineer a significant time gap between NO and Dox release, promoting MDR cancer therapy. A o-phenylenediamine-containing lipid that can hydrolyze in response to NO was embedded in the phospholipid bilayer structure of liposome to form NO-responsive liposome, which could further encapsulate l-arginine (l-Arg)/Dox-loaded gold@copper sulfide yolk-shell nanoparticls (ADAu@CuS YSNPs) to form ADLAu@CuS YSNPs. Under 808 nm laser irradiation, the unique resonant energy transfer (RET) process and reactive oxygen species (ROS) generation in the confined space of ADLAu@CuS YSNPs could effectively convert l-Arg into NO, regionally destabilizing the phospholipid bilayer structure, as a result of NO release. However, at this early stage Dox could not be released from YSNPs due to the molecular scaffold limit. As the NO release progressed, the NO-responsive liposome layer was deteriorated more severely, allowing Dox to escape. This NO and Dox sequential release of ADLAu@CuS YSNPs could significantly inhibit P-gp expression and enhance Dox accumulation in Dox-resistant MCF-7/ADR cells, leading to promising in vitro and in vivo therapeutic effects and presenting their great potential for MDR cancer therapy.

6.
Biomaterials ; 217: 119327, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31299626

RESUMO

Photochemotherapy is currently an effective anticancer therapy. Recently, it has been reported that cancer cells pretreated with epidermal growth factor receptor (EGFR) inhibitor erlotinib (Erl) can significantly synergize its apoptosis against the DNA damaging agent doxorubicin (Dox). As a result, we designed two gold nanocages (Au NCs) microcontainers covered with different smart polymer shell-PAA (pH responsive) and p (NIPAM-co-AM) (temperature responsive) containing Erl and Dox respectively. The acidic tumor microenvironment and NIR light irradiation can selectively activate the release of Erl and Dox. Time staggered release of Erl and Dox and photothermal therapy enhance the apoptotic signaling pathways, resulting in improved tumor cell killing in both MCF-7 (low EGFR expression) and A431 (very high EGFR expression) tumor cells, but more efficient in the latter. The photochemotherapy strategy controls the order and duration of drug exposure precisely in spatial and temporal, and significantly improves the therapeutic efficacy against high EGFR expressed tumors.

7.
Adv Healthc Mater ; 8(16): e1900256, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31290270

RESUMO

Wound healing is a complex and sequential biological process that involves multiple stages. Although various nanomaterials are applied to accelerate the wound healing process, only a single stage is promoted during the process, lacking hierarchical stimulation. Herein, hollow CeO2 nanoparticles (NPs) with rough surface and l-arginine inside (Ah CeO2 NPs) are developed as a compact and programmable nanosystem for sequentially promoting the hemostasis, inflammation, and proliferation stages. The rough surface of Ah CeO2 NPs works as a nanobridge to rapidly closure the wounds, promoting the hemostasis stage. The hollow structure of Ah CeO2 NPs enables the multireflection of light inside particles, significantly enhancing the light harvest efficiency and electron-hole pair abundance. Simultaneously, the porous shell of Ah CeO2 NPs facilitates the electron-hole separation and reactive oxygen species production, preventing wound infection and promotion wound healing during the inflammation stage. The enzyme mimicking property of Ah CeO2 NPs can alleviate the oxidative injury in the wound, and the released l-arginine can be converted into nitric oxide (NO) under the catalysis of inducible NO synthase, both of which promote the proliferation stage. A series of in vitro and in vitro biological assessments corroborate the effectiveness of Ah CeO2 NPs in the wound healing process.

8.
J Med Chem ; 62(15): 6985-6991, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31283215

RESUMO

Meta-iodobenzylguanidine (MIBG) is a ligand with high affinity against norepinephrine transporter (NET) that has been used for diagnostic imaging and radionuclide therapy of NET-expressing tumors, such as neuroblastoma. We hypothesize that MIBG can be used as a ligand for development of new anticancer drugs targeting NET-expressing neuroblastoma (NB). To test our hypothesis, we synthesized two MIBG-based anticancer copper complexes [Cu(m-TSBG)2 and Cu(p-TSBG)2] by conjugation of a thiosemicarbazone copper group onto MIBG ligand. Both Cu(m-TSBG)2 and Cu(p-TSBG)2 compounds showed potent anticancer activity against NB cells (BE2C and SK-N-DZ cells). The NB-specific anticancer activity of Cu(m-TSBG)2 and Cu(p-TSBG)2 was further demonstrated by the reduced anticancer activities when nonconjugated MIBG ligand was used to competitively block binding of Cu(m-TSBG)2 or Cu(p-TSBG)2 onto NET-expressing NB cells. Both Cu(m-TSBG)2 or Cu(p-TSBG)2 compounds hold potential as promising new drugs for targeted therapy of neuroblastoma and other NET-expressing tumors.

9.
Adv Sci (Weinh) ; 6(11): 1900158, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31179221

RESUMO

The development of sophisticated theranostic systems for simultaneous near infrared (NIR) fluorescence imaging and phototherapy is of particular interest. Herein, anisotropic plasmonic metal heterostructures, Pt end-deposited Au nanorods (PEA NRs), are developed to efficiently produce hot electrons under 808 nm laser irradiation, exhibiting the strong electric density. These hot electrons can release the heat through electron-phonon relaxation and form reactive oxygen species through chemical transformation, as a result of potent photothermal and photodynamic performance. Simultaneously, the confined electromagnetic field of PEA NRs can transfer energy to adjacent polyethylene glycol (PEG)-linked NIR fluorophores (CF) based on their energy overlap mechanism, leading to remarkable NIR fluorescence amplification in CF-PEA NRs. Various PEG linkers (1, 3.4, 5.0, and 10 kD) are employed to regulate the distance between CF and PEA NRs of CF-PEA NRs, and the maximum fluorescence intensity is achieved in CF5k-PEA NRs. After further attachment with i-motif DNA/Nrf2 siRNA chimera to simultaneously suppress both cellular antioxidant defense and hyperthermia resistance effects, the final biocompatible CF5k-bPEA@siRNA NRs present promising NIR fluorescence imaging ability and 808 nm laser-activated photothermal and photodynamic therapeutic effect in MCF7 cells and tumor-bearing mice, holding great potential for cancer therapy.

10.
Nano Lett ; 19(7): 4478-4489, 2019 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-31244230

RESUMO

Silver nanoparticles (Ag NPs) have promising plasmonic properties, however, they are rarely used in biomedical applications because of their potent toxicity. Herein, an electron compensation effect from Au to Ag was applied to design safe Au@Ag core-shell NPs. The Ag shell thickness was precisely regulated to enable the most efficient electron enrichment in Ag shell of Au@Ag2.4 NPs, preventing Ag oxidation and subsequent Ag+ ion release. X-ray photoelectron spectroscopy and X-ray absorption near-edge structure analysis revealed the electron transfer process from Au core to Ag shell, and inductively coupled plasma optical emission spectroscopy analysis confirmed the low Ag+ ion release from Au@Ag2.4 NPs. Bare Au@Ag2.4 NPs showed much lower toxicological responses than Ag NPs in BEAS-2B and Raw 264.7 cells and acute lung inflammation mouse models, and PEGylation of Au@Ag2.4 NPs could further improve their safety to L02 and HEK293T cells as well as mice through intravenous injection. Further, diethylthiatri carbocyanine iodide attached pAu@Ag2.4 NPs exhibited intense surface-enhanced Raman scattering signals and were used for Raman imaging of MCF7 cells and Raman biosensing in MCF7 tumor-bearing mice. This electron compensation effect opens up new opportunity for broadening biomedical application of Ag-based NPs.

11.
Nano Lett ; 19(6): 4134-4145, 2019 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-31084016

RESUMO

As a noninvasive treatment modality, ultrasound (US)-triggered sonodynamic therapy (SDT) shows broad and promising applications to overcome the drawbacks of traditional photodynamic therapy (PDT) in combating cancer. However, the SDT efficacy is still not satisfactory without oxygen (O2) assistance. In addition, there is also much space to explore the SDT-based synergistic therapeutic modalities. Herein, a novel Pt-CuS Janus composed of hollow semiconductor CuS and noble metallic Pt was rationally designed and successfully synthesized. The hollow CuS shows a large inner cavity for loading sonosensitizer molecules (tetra-(4-aminophenyl) porphyrin, TAPP) to implement SDT. Moreover, the deposition of Pt not only enhances photothermal performance compared with those of CuS nanoparticles (NPs) due to the effect of the local electric field enhancement but also possesses nanozyme activity for catalyzing decomposition of endogenous overexpressed hydrogen peroxide (H2O2) to produce O2 that can overcome tumor hypoxia and augment the SDT-induced highly toxic reactive oxygen species (ROS) production for efficient cancer cell apoptosis. Importantly, the generated heat of Pt-CuS by 808 nm laser irradiation can accelerate the catalytic activity of Pt and elevate the O2 level that further facilitates SDT efficacy. Interestingly, the thermally sensitive copolymer coated around the Janus can act as a smart switch to regulate the catalytic ability of Pt and control TAPP release that has a significant effect on modulating the therapeutic effect. The synergistic catalysis-enhanced SDT efficiency and highly photothermal effect almost realized complete tumor resection without obvious reoccurrence and simultaneously displayed a highly therapeutic biosafety. Furthermore, the high optical absorbance allows the as-synthesized Pt-CuS Janus for photoacoustic (PA) imaging and NIR thermal imaging. This work develops a versatile nanoplatform for a multifunctional theranostic strategy and broadens the biological applications by rationally designing their structure.


Assuntos
Neoplasias do Colo/terapia , Cobre/uso terapêutico , Nanopartículas/uso terapêutico , Platina/uso terapêutico , Animais , Linhagem Celular Tumoral , Humanos , Hipertermia Induzida , Camundongos , Nanopartículas/ultraestrutura , Hipóxia Tumoral , Terapia por Ultrassom
12.
Gene ; 707: 44-52, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-30898716

RESUMO

Long non-coding RNAs (lncRNAs) have been wildly verified to modulate multiple tumorigenesis, especially nasopharyngeal carcinoma (NPC). In present study, we aims to investigate the role and mechanism of LINC00520 in the NPC carcinogenesis. Results indicated that LINC00520 was significantly increasing in NPC tissues and cells in comparison to their corresponding controls. Moreover, the aberrant overexpression of LINC00520 indicated the poor prognosis of NPC patients. Silence of LINC00520 was able to repress NPC cell growth in vitro while overexpression of LINC00520 inversed this process. Moreover, in vivo tumor xenografts were establishing using CNE-1/SUNE-1 cells to investigate the function of LINC00520 in NPC tumorigenesis. Rescue assay was conducting to further confirm that LINC00520 contributed to NPC progression by regulating miR-26b-3p/ubiquitin-specific protease 39 (USP39) signal pathway. Taken together, our study discovered the oncogenic role of LINC00520 in clinical specimens and cellular experiments, showing the potential LINC00520/miR-26b-3p/USP39 pathway. This results and findings provide a novel insight for NPC tumorigenesis.


Assuntos
MicroRNAs/genética , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , RNA Longo não Codificante/genética , Proteases Específicas de Ubiquitina/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Transplante de Neoplasias , Prognóstico , Proteases Específicas de Ubiquitina/metabolismo , Regulação para Cima
13.
Expert Rev Proteomics ; 16(5): 413-429, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30925852

RESUMO

INTRODUCTION: Resistance to chemotherapy and development of specific and effective molecular targeted therapies are major obstacles facing current cancer treatment. Comparative proteomic approaches have been employed for the discovery of putative biomarkers associated with cancer drug resistance and have yielded a number of candidate proteins, showing great promise for both novel drug target identification and personalized medicine for the treatment of drug-resistant cancer. Areas covered: Herein, we review the recent advances and challenges in proteomics studies on cancer drug resistance with an emphasis on biomarker discovery, as well as understanding the interconnectivity of proteins in disease-related signaling pathways. In addition, we highlight the critical role that post-translational modifications (PTMs) play in the mechanisms of cancer drug resistance. Expert opinion: Revealing changes in proteome profiles and the role of PTMs in drug-resistant cancer is key to deciphering the mechanisms of treatment resistance. With the development of sensitive and specific mass spectrometry (MS)-based proteomics and related technologies, it is now possible to investigate in depth potential biomarkers and the molecular mechanisms of cancer drug resistance, assisting the development of individualized therapeutic strategies for cancer patients.

14.
ACS Appl Mater Interfaces ; 11(13): 12224-12231, 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30864776

RESUMO

Silver (Ag)-based nanoparticles (NPs) with a high potential of Ag+ release have been known to be capable of promoting bacteria inactivation and the wound healing process; however, keeping a steady flux of high levels of Ag+ in Ag-based NPs is still challenging. Herein, a novel strategy in terms of altering the intrinsic electronic structure of Ag NPs was attempted to facilitate Ag oxidation and boost the Ag+ flux, as results of improved antibacterial and wound healing performance of Ag NPs. Gold (Au), platinum (Pt), and palladium (Pd) were doped into Ag NPs to tune their d band centers to upshift toward the Fermi level, and the formed Pd-Ag alloy NPs showed the largest shift, followed by Pt-Ag and Au-Ag NPs, as determined by density function theory calculation and ultraviolet photoemission spectroscopy measurement. Further X-ray photoelectron spectroscopy analysis indicates that a larger upshift could induce less electron filling in the antibonding orbital and a higher Ag oxidation level, leading to the more remarkable Ag+ release as determined by inductively coupled plasma optical emission spectrometry. All these alloy Ag NPs could more efficiently inhibit bacterial growth and accelerate the wound healing process than pure Ag NPs, and their antibacterial activity and wound healing performance were progressively proportional to the upshift values of the d band center. Taken together, tuning the d band center to upshift toward the Fermi level becomes a feasible strategy for designing therapeutic Ag-based NPs with a promising antibacterial and wound healing performance.


Assuntos
Ligas , Antibacterianos , Nanopartículas Metálicas , Prata , Cicatrização/efeitos dos fármacos , Ligas/química , Ligas/farmacocinética , Ligas/farmacologia , Animais , Antibacterianos/química , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Feminino , Ouro/química , Ouro/farmacologia , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Células NIH 3T3 , Paládio/química , Paládio/farmacologia , Prata/química , Prata/farmacocinética , Prata/farmacologia
15.
Biomater Sci ; 7(4): 1448-1462, 2019 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-30666994

RESUMO

Various gold (Au) nanostructures have shown promising near infrared (NIR) light-activated phototherapeutic effects; however, their reported photothermal or photodynamic performance behavior is usually inconsistent or even conflicted, dramatically limiting the improvement of phototherapeutic Au nanostructures. The potential reason for this uncertainty is mainly because the photoactivities of Au nanostructures are not evaluated under identical energy conditions. Herein, three Au nanostructures, Au nanorods (NRs), nanoshells (NSs), and nanocages (NCs), were prepared to provide the same localized surface plasmon resonance (LSPR) peaks at 808 nm. All these Au nanostructures (at the same optical density) could fully exert their photoactivities under the identical and optimal energy conditions of 808 nm laser irradiation. It was found that these Au nanostructures could induce similar levels of temperature elevation but different levels of reactive oxygen species (ROS) production, where Au NCs exhibited the highest ROS production, followed by Au NSs and NRs. In vitro and in vivo phototherapeutic assessments further supported that Au NCs could cause the most severe cell death and tumor growth regression. This means that the identical incident energy has different contributions to the photothermal and photodynamic performance of Au nanostructures, and the corner angle structures of Au NCs compared with NSs and NCs could more efficiently convert the photon energy into photodynamic properties. Altogether, Au NCs hold great potential for phototherapy due to their efficient energy utilization capability.


Assuntos
Antineoplásicos/farmacologia , Ouro/farmacologia , Lasers , Nanoestruturas/química , Fototerapia , Animais , Antineoplásicos/química , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Ouro/química , Camundongos , Tamanho da Partícula , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismo , Propriedades de Superfície , Células Tumorais Cultivadas
16.
Adv Mater ; 31(10): e1806808, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30633400

RESUMO

Bismuth (Bi)-based nanomaterials (NMs) are widely used for computed tomography (CT) imaging guided photothermal therapy, however, the photodynamic property is hardly exhibited by these NMs due to the fast electron-hole recombination within their narrow bandgap. Herein, a sophisticated nanosystem is designed to endow bismuth sulfide (Bi2 S3 ) nanorods (NRs) with potent photodynamic property. Zinc protoporphyrin IX (ZP) is linked to Bi2 S3 NRs through a thermoresponsive polymer to form BPZP nanosystems. The stretching ZP could prebind to the active site of heme oxygenase-1 overexpressed in cancer cells, suppressing the cellular antioxidant defense capability. Upon NIR laser irradiation, the heat released from Bi2 S3 NRs could retract the polymer and drive ZP to the proximity of Bi2 S3 NRs, facilitating an efficient electron-hole separation in ZP and Bi2 S3 NRs, and leading to reactive oxygen species generation. In vitro and in vivo studies demonstrate the promising photodynamic property of BPZP, together with their photothermal and CT imaging performance.


Assuntos
Antioxidantes/metabolismo , Nanoestruturas/ultraestrutura , Nanotubos/química , Protoporfirinas/química , Animais , Bismuto/química , Humanos , Fototerapia/métodos , Sulfetos/química , Nanomedicina Teranóstica/métodos
17.
Chem Commun (Camb) ; 54(92): 12990-12993, 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30387478
18.
ACS Appl Mater Interfaces ; 10(40): 34655-34663, 2018 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-30226739

RESUMO

Multifunctional supramolecular nanomaterials capable of targeted and multimodal therapy hold great potential to improve the efficiency of cancer therapeutics. Herein, we report a proof-of-concept nanoplatform for effective chemophotothermal therapy via the integration of folic acid-based active targeting and supramolecular nanovalves-based passive targeting. Inspired by facile surface engineering and designable layer-by-layer assembly concept, we design and synthesize PPy@UiO-66@WP6@PEI-Fa nanoparticles (PUWPFa NPs) to achieve efficient synergistic chemophotothermal therapy, taking advantage of the desirable photothermal conversion capability of polypyrrole nanoparticles (PPy NPs) and high drug-loading capacity of hybrid scaffolds. Significantly, pillararene-based pseudorotaxanes as pH/temperature dual-responsive nanovalves allow targeted drug delivery in pathological environment with sustained release over 4 days, which is complementary to photothermal therapy, and folic acid-conjugated polyethyleneimine (PEI-Fa) at the outmost layer through electrostatic interactions is able to enhance tumor-targeting and therapeutic efficiency. Such PUWPFa NPs showed efficient synergistic chemophotothermal therapy of cervical cancer both in vitro and in vivo. The present strategy offers not only the distinctly targeted drug delivery and release, but also excellent tumor inhibition efficacy of simultaneous chemophotothermal therapy, opening a new avenue for effective cancer treatment.

19.
Ecotoxicol Environ Saf ; 163: 612-619, 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30092543

RESUMO

Airborne fine particulate matter (PM2.5) has been known capable of causing lung inflammation and fibrosis, as a result of a series of chronic respiration diseases. Although NLRP3 inflammasome activation is essential for development of many chronic diseases, the relationship between PM2.5-induced toxicological effect and NLRP3 inflammasome activation is rarely investigated. Since PM2.5 contains a large population of nanosized materials and many types of nanomaterials can activate NLRP3 inflammasome, the NLRP3 inflammasome activation and lung fibrosis induced by PM2.5 were investigated in the present study. PM2.5 was found capable of causing weak cell death but potent IL-1ß secretion in THP-1 cells, which was involved in NLRP3 inflammasome activation as evidenced by Z-YVAD-FMK inhibited IL-1ß secretion and overexpressed ASC and NLRP3 protein in PM2.5 treated cells. PM2.5 could be internalized into cells through multiple endocytosis processes, such as phagocytosis and pinocytosis (macropinocytosis, clathrin- and caveolin-mediated endocytosis), and activate NLRP3 inflammasome through cathepsin B release, ROS production, and potassium efflux. After 21 days of exposure to PM2.5 through oropharyngeal aspiration, Balb/c mice showed increased IL-1ß and TGF-ß1 levels in the bronchoalveolar lavage fluid (BALF) of lung and significant collagen deposition around small airways of mice, suggesting potential lung inflammation and pulmonary fibrosis.


Assuntos
Inflamassomos/metabolismo , Pulmão/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Material Particulado/toxicidade , Fibrose Pulmonar/induzido quimicamente , Animais , Linhagem Celular , Humanos , Inflamassomos/fisiologia , Interleucina-1beta/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pneumonia/induzido quimicamente
20.
Chemistry ; 24(66): 17405-17418, 2018 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-29876975

RESUMO

Theranostic nanomaterials (NMs) have gained increasing attention for their simultaneous performance of diagnosis and therapy. Bi-based NMs hold great potential as theranostic platforms based on their X-ray sensitive capability, near-infrared driven semiconductor properties, and distinctive structures, which facilitate the computed tomography (CT) imaging, photoacoustic (PA) imaging, radiation therapy, and phototherapy. The sophisticated design in composition, structure, and surface fabrication of Bi-based NMs can endow these NMs with more modalities in cancer diagnosis and therapy. In this Minireview, we focus on the recent advances in Bi-based theranostic NMs. A series of unique structures and functions as well as the underlying property-activity relationship of Bi-based NMs are showcased to highlight their promising imaging and therapeutic performance. At the end, we propose some challenges for the design and preparation of Bi-based NMs to improve their cancer diagnostic and therapeutic performance.


Assuntos
Bismuto/química , Nanoestruturas/química , Neoplasias/diagnóstico , Animais , Humanos , Neoplasias/radioterapia , Técnicas Fotoacústicas , Fototerapia , Espécies Reativas de Oxigênio/metabolismo , Nanomedicina Teranóstica , Tomografia Computadorizada por Raios X
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