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1.
J Mater Sci Mater Med ; 32(9): 108, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34432156

RESUMO

Surface modification of superparamagnetic Fe3O4 nanoparticles using polymers (polyaniline/polypyrrole) was done by radio frequency (r.f.) plasma polymerization technique and characterized by XRD, TEM, TG/DTA and VSM. Surface-passivated Fe3O4 nanoparticles with polymers were having spherical/rod-shaped structures with superparamagnetic properties. Broad visible photoluminescence emission bands were observed at 445 and 580 nm for polyaniline-coated Fe3O4 and at 488 nm for polypyrrole-coated Fe3O4. These samples exhibit good fluorescence emissions with L929 cellular assay and were non-toxic. Magnetic hyperthermia response of Fe3O4 and polymer (polyaniline/polypyrrole)-coated Fe3O4 was evaluated and all the samples exhibit hyperthermia activity in the range of 42-45 °C. Specific loss power (SLP) values of polyaniline and polypyrrole-coated Fe3O4 nanoparticles (5 and 10 mg/ml) exhibit a controlled heat generation with an increase in the magnetic field.


Assuntos
Compostos de Anilina/química , Diagnóstico por Imagem/métodos , Hipertermia Induzida/métodos , Nanopartículas de Magnetita/química , Polímeros/química , Pirróis/química , Compostos de Anilina/efeitos da radiação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Compostos Férricos/síntese química , Compostos Férricos/química , Compostos Férricos/efeitos da radiação , Humanos , Campos Magnéticos , Magnetismo/métodos , Nanopartículas de Magnetita/efeitos da radiação , Nanopartículas de Magnetita/uso terapêutico , Teste de Materiais , Gases em Plasma/química , Polímeros/efeitos da radiação , Pirróis/efeitos da radiação , Ondas de Rádio , Propriedades de Superfície/efeitos da radiação , Difração de Raios X
2.
ACS Appl Mater Interfaces ; 13(28): 32690-32702, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34229434

RESUMO

The synergistic nanotheranostics of reactive oxygen species (ROS) augment or phototherapy has been a promising method within synergistic oncotherapy. However, it is still hindered by sophisticated design and fabrication, lack of a multimodal synergistic effect, and hypoxia-associated poor photodynamic therapy (PDT) efficacy. Herein, a kind of porous shuttle-shape platinum (IV) methylene blue (Mb) coordination polymer nanotheranostics-loaded 10-hydroxycamptothecin (CPT) is fabricated to address the abovementioned limitations. Our nanoreactors possess spatiotemporally controlled O2 self-supply, self-sufficient singlet oxygen (1O2), and outstanding photothermal effect. Once they are taken up by tumor cells, nanoreactors as a cascade catalyst can efficiently catalyze degradation of the endogenous hydrogen peroxide (H2O2) into O2 to alleviate tumor hypoxia. The production of O2 can ensure enhanced PDT. Subsequently, under both stimuli of external red light irradiation and internal lysosomal acidity, nanoreactors can achieve the on-demand release of CPT to augment in situ mitochondrial ROS and highly efficient tumor ablation via phototherapy. Moreover, under the guidance of near-infrared (NIR) fluorescent imaging, our nanoreactors exhibit strongly synergistic potency for treatment of hypoxic tumors while reducing damages against normal tissues and organs. Collectively, shuttle-shape platinum-coordinated nanoreactors with augmented ROS capacity and enhanced phototherapy efficiency can be regarded as a novel tumor theranostic agent and further promote the research of synergistic oncotherapy.


Assuntos
Antineoplásicos/uso terapêutico , Camptotecina/análogos & derivados , Portadores de Fármacos/química , Nanoestruturas/química , Neoplasias/tratamento farmacológico , Hipóxia Tumoral/efeitos dos fármacos , Animais , Antineoplásicos/química , Camptotecina/química , Camptotecina/uso terapêutico , Catálise/efeitos da radiação , Linhagem Celular Tumoral , Portadores de Fármacos/efeitos da radiação , Liberação Controlada de Fármacos , Feminino , Humanos , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , Luz , Azul de Metileno/análogos & derivados , Azul de Metileno/efeitos da radiação , Camundongos Endogâmicos BALB C , Nanoestruturas/efeitos da radiação , Neoplasias/metabolismo , Oxigênio/metabolismo , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Terapia Fototérmica , Platina/química , Platina/efeitos da radiação , Polímeros/síntese química , Polímeros/química , Polímeros/efeitos da radiação , Porosidade , Oxigênio Singlete/metabolismo , Nanomedicina Teranóstica
3.
ACS Appl Mater Interfaces ; 13(8): 10287-10300, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33615773

RESUMO

Near-infrared (NIR)-light-modulated photothermal thrombolysis has been investigated to overcome the hemorrhage danger posed by clinical clot-busting substances. A long-standing issue in thrombosis fibrinolytics is the lack of lesion-specific therapy, which should not be ignored. Herein, a novel thrombolysis therapy using photothermal disintegration of a fibrin clot was explored through dual-targeting glycol chitosan/heparin-decorated polypyrrole nanoparticles (GCS-PPY-H NPs) to enhance thrombus delivery and thrombolytic therapeutic efficacy. GCS-PPY-H NPs can target acidic/P-selectin high-expression inflammatory endothelial cells/thrombus sites for initiating lesion-site-specific thrombolysis by hyperthermia using NIR irradiation. A significant fibrin clot-clearance rate was achieved with thrombolysis using dual-targeting/modality photothermal clot disintegration in vivo. The molecular level mechanisms of the developed nanoformulations and interface properties were determined using multiple surface specific analytical techniques, such as particle size distribution, zeta potential, electron microscopy, Fourier-transform infrared spectroscopy (FTIR), wavelength absorbance, photothermal, immunofluorescence, and histology. Owing to the augmented thrombus delivery of GCS-PPY-H NPs and swift treatment time, dual-targeting photothermal clot disintegration as a systematic treatment using GCS-PPY-H NPs can be effectively applied in thrombolysis. This novel approach possesses a promising future for thrombolytic treatment.


Assuntos
Quitosana/uso terapêutico , Heparina/uso terapêutico , Nanopartículas/uso terapêutico , Polímeros/uso terapêutico , Pirróis/uso terapêutico , Trombose/tratamento farmacológico , Animais , Quitosana/química , Células Endoteliais/metabolismo , Heparina/química , Heparina/metabolismo , Luz , Masculino , Camundongos Endogâmicos ICR , Nanopartículas/química , Nanopartículas/efeitos da radiação , Selectina-P/metabolismo , Fototerapia/métodos , Polímeros/química , Polímeros/efeitos da radiação , Pirróis/química , Pirróis/efeitos da radiação , Terapia Trombolítica/métodos , Trombose/metabolismo
4.
J Mater Sci Mater Med ; 31(7): 58, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32607849

RESUMO

Traumatic spinal cord injury (TSCI) can cause paralysis and permanent disability. Rehabilitation (RB) is currently the only accepted treatment, although its beneficial effect is limited. The development of biomaterials has provided therapeutic possibilities for TSCI, where our research group previously showed that the plasma-synthesized polypyrrole/iodine (PPy/I), a biopolymer with different physicochemical characteristics than those of the PPy synthesized by conventional methods, promotes recovery of motor function after TSCI. The present study evaluated if the plasma-synthesized PPy/I applied in combination with RB could increase its beneficial effects and the mechanisms involved. Adult rats with TSCI were divided into no treatment (control); biopolymer (PPy/I); mixed RB by swimming and enriched environment (SW/EE); and combined treatment (PPy/I + SW/EE) groups. Eight weeks after TSCI, the general health of the animals that received any of the treatments was better than the control animals. Functional recovery evaluated by two scales was better and was achieved in less time with the PPy/I + SW/EE combination. All treatments significantly increased ßIII-tubulin (nerve plasticity) expression, but only PPy/I increased GAP-43 (nerve regeneration) and MBP (myelination) expression when were analyzed by immunohistochemistry. The expression of GFAP (glial scar) decreased in treated groups when determined by histochemistry, while morphometric analysis showed that tissue was better preserved when PPy/I and PPy/I + SW/EE were administered. The application of PPy/I + SW/EE, promotes the preservation of nervous tissue, and the expression of molecules related to plasticity as ßIII-tubulin, reduces the glial scar, improves general health and allows the recovery of motor function after TSCI. The implant of the biomaterial polypyrrole/iodine (PPy/I) synthesized by plasma (an unconventional synthesis method), in combination with a mixed rehabilitation scheme with swimming and enriched environment applied after a traumatic spinal cord injury, promotes expression of GAP-43 and ßIII-tubulin (molecules related to plasticity and nerve regeneration) and reduces the expression of GFAP (molecule related to the formation of the glial scar). Both effects together allow the formation of nerve fibers, the reconnection of the spinal cord in the area of injury and the recovery of lost motor function. The figure shows the colocalization (yellow) of ßIII-tubilin (red) and GAP-43 (green) in fibers crossing the epicenter of the injury (arrowheads) that reconnect the rostral and caudal ends of the injured spinal cord and allowed recovery of motor function.


Assuntos
Materiais Biocompatíveis , Terapia por Exercício/métodos , Iodo/química , Polímeros/química , Pirróis/química , Traumatismos da Medula Espinal/reabilitação , Traumatismos da Medula Espinal/cirurgia , Animais , Coagulação com Plasma de Argônio/métodos , Materiais Biocompatíveis/administração & dosagem , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/efeitos da radiação , Precipitação Química/efeitos da radiação , Terapia Combinada , Modelos Animais de Doenças , Planejamento Ambiental , Feminino , Injeções Espinhais , Iodo/administração & dosagem , Iodo/efeitos da radiação , Laminectomia , Lasers de Gás/uso terapêutico , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Regeneração Nervosa/efeitos dos fármacos , Regeneração Nervosa/fisiologia , Polímeros/administração & dosagem , Polímeros/síntese química , Polímeros/efeitos da radiação , Pirróis/administração & dosagem , Pirróis/síntese química , Pirróis/efeitos da radiação , Ratos , Ratos Long-Evans , Recuperação de Função Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/fisiologia , Traumatismos da Medula Espinal/patologia , Regeneração da Medula Espinal/efeitos dos fármacos , Natação
5.
ACS Appl Mater Interfaces ; 12(20): 23311-23322, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32349481

RESUMO

Dendritic macromolecules are potential candidates for nanomedical application. Herein, glycogen, the natural hyperbranched polysaccharide with favorable biocompatibility, is explored as an effective drug vehicle for treating liver cancer. In this system, glycogen is oxidized and conjugated with cancer drugs through a disulfide link, followed by in situ loading of polypyrrole nanoparticles and then coated with functional phospholipids to form the desired system, Gly-ss-DOX@ppy@Lipid-RGD. The phospholipid layer has good cell affinity and can assist the system to penetrate into cells smoothly. Additionally, combined with the "fusion targeting" of glycogen and the active targeting effect of RGD toward liver cancer cells, Gly-ss-DOX@ppy@Lipid-RGD presents efficient specificity and enrichment of hepatocellular carcinoma. Owing to the glutathione-triggered cleavage of disulfide linkers, Gly-ss-DOX@ppy@Lipid-RGD can controllably release drugs to induce cell nucleus damage. Meanwhile, the polypyrrole nanoparticles can absorb near-infrared light and radiate heat energy within tumors. Besides enhancing drug release, the heat can also provide photothermal treatment for tumors. As proved by in vitro and in vivo experiments, Gly-ss-DOX@ppy@Lipid-RGD is a remarkable candidate for synergistic chemophotothermal therapy with high anticancer therapeutic activity and reduced systematic toxicity, efficiently suppressing tumor growth. All results demonstrate that glycogen nanoparticles are expected to be a new building block for accurate hepatocellular carcinoma treatment.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Doxorrubicina/uso terapêutico , Glicogênio/química , Neoplasias Hepáticas/tratamento farmacológico , Nanopartículas/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Terapia Combinada , Doxorrubicina/química , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Glicogênio/toxicidade , Hemólise/efeitos dos fármacos , Humanos , Hipertermia Induzida/métodos , Raios Infravermelhos , Camundongos Endogâmicos BALB C , Nanopartículas/efeitos da radiação , Nanopartículas/toxicidade , Fosfolipídeos/química , Fosfolipídeos/toxicidade , Fotoquimioterapia , Polímeros/química , Polímeros/efeitos da radiação , Polímeros/toxicidade , Pirróis/química , Pirróis/efeitos da radiação , Pirróis/toxicidade
6.
ACS Appl Mater Interfaces ; 12(22): 24611-24622, 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32379418

RESUMO

Although differently shaped mesoporous silica is widely studied, the formation of width-consistent mesoporous silica nanorods (MSNRs) with a precisely controlled aspect ratio (AR: length/width) is challenging and has not been reported. Herein, width-consistent (100 nm) MSNRs with ARs of 2, 3, 4, 6, 8, and 10 were obtained by increasing the concentrations while maintaining the molar ratio of cetyltrimethylammonium bromide (CTAB) and tetraethyl orthosilicate (TEOS). The results demonstrated that the as-prepared MSNR with an AR of 6 (AR6) possesses high cellular-uptake efficiency and drug-loading capacity. Thus, AR6-based cancer-cell-targeting nanosystems were designed. These nanosystems encapsulated doxorubicin (DOX) into the porous channel of AR6, adsorbed glucose oxidase (GOx), and then formed a polydopamine (PDA) layer for Siramesine (Siram, a lysosome dysfunctional drug) adsorption and folic acid modification. In this design, the PDA shell could prevent the leakage of loading components and keep the activity of GOx during delivery while achieving an on-demand drug release in the targeted location and photothermal therapy under near-infrared irradiation. The increase in temperature was highly beneficial for elevating the catalytic efficiency of GOx, accelerating the consumption of intracellular glucose, and generating a relatively high level of cytotoxic H2O2, all of which enhanced starvation and oxidative therapies. Siram was employed to inhibit lysosomal metabolism and accompany GOx to reach a dual-enhanced starvation therapy effect. In addition, DOX entered the nucleus and altered DNA for chemotherapy. The results showed that the nanosystems have superior therapeutic efficacy against cancer cells and not much toxicity to normal cells. Therefore, this study provides a novel strategy for lysosome dysfunctional synergistic chemotherapy/photothermal therapy/starvation therapy/oxidative therapy based on MSNR.


Assuntos
Antineoplásicos/farmacologia , Terapia Combinada/métodos , Portadores de Fármacos/química , Lisossomos/efeitos dos fármacos , Nanotubos/química , Dióxido de Silício/química , Adsorção , Doxorrubicina/farmacologia , Glucose Oxidase/farmacologia , Células Hep G2 , Humanos , Hipertermia Induzida/métodos , Indóis/química , Indóis/farmacologia , Indóis/efeitos da radiação , Raios Infravermelhos , Fotoquimioterapia/métodos , Polímeros/química , Polímeros/efeitos da radiação , Porosidade , Compostos de Espiro/farmacologia
7.
ACS Appl Mater Interfaces ; 12(23): 26432-26443, 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32429664

RESUMO

The development of a highly effective photosensitizer (PS) that can be activated with a low-power single light is a pressing issue. Herein, we report a PS for synergistic photodynamic and photothermal therapy constructed through self-assembly of poly(selenoviologen) on the surface of core-shell NaYF4:Yb/Tm@NaYF4 upconversion nanoparticles. The hybrid UCNPs/PSeV PS showed strong ROS generation ability and high photothermal conversion efficiency (∼52.5%) under the mildest reported-to-date irradiation conditions (λ = 980 nm, 150 mW/cm2, 4 min), leading to a high efficiency in killing methicillin-resistant Staphylococcus aureus (MRSA) both in vitro and in vivo. Remarkably, after intravenous injection, the reported PS accumulated preferentially in deep MRSA-infected tissues and achieved an excellent therapeutic index. This PS design realizes a low-power single-NIR light-triggered synergistic phototherapy and provides a simple and versatile strategy to develop safe clinically translatable agents for efficient treatment of deep tissue bacterial inflammations.


Assuntos
Antibacterianos/uso terapêutico , Nanopartículas/uso terapêutico , Compostos Organosselênicos/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Viologênios/uso terapêutico , Animais , Antibacterianos/química , Antibacterianos/efeitos da radiação , Fluoretos/química , Fluoretos/efeitos da radiação , Hipertermia Induzida/métodos , Raios Infravermelhos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Nanopartículas/química , Nanopartículas/efeitos da radiação , Compostos Organosselênicos/química , Compostos Organosselênicos/efeitos da radiação , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/efeitos da radiação , Polímeros/química , Polímeros/efeitos da radiação , Polímeros/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Túlio/química , Túlio/efeitos da radiação , Viologênios/química , Viologênios/efeitos da radiação , Itérbio/química , Itérbio/efeitos da radiação , Ítrio/química , Ítrio/efeitos da radiação
8.
ACS Appl Mater Interfaces ; 12(20): 22613-22623, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32338491

RESUMO

Small interfering RNA (siRNA)-induced gene therapy has been recognized as a promising avenue for effective cancer treatment, while easy enzymatic degradation, poor transfection efficiency, nonspecific biodistribution, and uncontrolled release hinder its extensive clinical applications. Zeolitic imidazolate frameworks-8 (ZIF-8) have emerged as promising drug carriers without an in-depth exploration in programmable siRNA delivery. Herein, we report a multifunctional PDAs-ZIF-8 (PZ) nanoplatform for delivering siRNA with combined photothermal therapy (PTT) and gene therapy (GT) via the noninvasive guidance of photoacoustic (PA)/near-infrared (IR) dual-modal imaging. The ingenious PZ nanocarriers mediated the tumor-specific accumulation of therapeutic siRNA without undesired degradation and preleakage. The pH-responsive ZIF-8 decomposed in an acidic tumor microenvironment that was accompanied by the release of siRNA payloads for cleaving target mRNA in gene silencing therapy. Meanwhile, the polydopamine nanoparticles (PDAs) could simultaneously serve as a powerful noninvasive PA/IR imaging contrast agent and versatile photothermal agent for diagnosis-guided photogenetherapy. The systematic in vitro and in vivo experimental explorations demonstrated that our PDAs-siRNA-ZIF-8 (PSZ) could greatly enhance the therapeutic efficiency as compared with the corresponding PTT or GT monotherapy. This work holds great potential to advance the development of more intelligent diagnosis and therapeutic strategies, thus supplying promising smart nanomedicines in the near future.


Assuntos
Antineoplásicos/uso terapêutico , Meios de Contraste/química , Portadores de Fármacos/química , Nanopartículas/química , Neoplasias/tratamento farmacológico , RNA Interferente Pequeno/uso terapêutico , Animais , Terapia Combinada/métodos , Meios de Contraste/efeitos da radiação , Portadores de Fármacos/efeitos da radiação , Inativação Gênica/efeitos dos fármacos , Terapia Genética , Hipertermia Induzida/métodos , Indóis/química , Indóis/efeitos da radiação , Raios Infravermelhos , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/efeitos da radiação , Camundongos Endogâmicos BALB C , Nanopartículas/efeitos da radiação , Fototerapia/métodos , Polímeros/química , Polímeros/efeitos da radiação , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Angew Chem Int Ed Engl ; 59(31): 12756-12761, 2020 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-32343868

RESUMO

Cancer possesses normoxic and hypoxia microenvironments with different levels of oxygen, needing different efficacies of photothermal and photodynamic therapies. It is important to precisely tune the photothermal and photodynamic effects of phototherapy nano-agents for efficient cancer treatment. Now, a series of copolymeric nanoparticles (PPy-Te NPs) were synthesized in situ by controlled oxidative copolymerization with different ratios of pyrrole to tellurophene by FeCl3 . The photothermal and photodynamic effects of semiconducting nano-agents under the first near-infrared (NIR) irradiation were precisely and systematically tuned upon simply varying the molar ratio of the pyrrole to tellurophene. The PPy-Te NPs were used for cancer treatment in mice, exhibiting excellent biocompatibility and therapeutic effect. This work presents a simple method to tune photothermal and photodynamic therapies effect in semiconducting nano-agents for cancer treatment.


Assuntos
Antineoplásicos/uso terapêutico , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Polímeros/uso terapêutico , Pirróis/uso terapêutico , Animais , Antineoplásicos/síntese química , Antineoplásicos/efeitos da radiação , Linhagem Celular Tumoral , Raios Infravermelhos , Camundongos , Nanopartículas/química , Nanopartículas/efeitos da radiação , Fotoquimioterapia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/efeitos da radiação , Terapia Fototérmica , Polimerização , Polímeros/síntese química , Polímeros/efeitos da radiação , Pirróis/síntese química , Pirróis/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo
10.
Chem Commun (Camb) ; 56(7): 1093-1096, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31894764

RESUMO

We prepared novel conjugated polymer based NIR-II nanoparticles, which display extremely high photothermal conversion efficiency (65%). Both in vitro and in vivo investigations revealed that the as-prepared nanoparticles exhibit excellent theranostic properties including an extremely high cancer cell killing ability, admirable tumor elimination efficiency (100%) and a remarkable photoacoustic imaging contrast enhancing ability.


Assuntos
Antineoplásicos/uso terapêutico , Nanopartículas/uso terapêutico , Compostos de Organossilício/uso terapêutico , Polímeros/uso terapêutico , Tiadiazóis/uso terapêutico , Animais , Antineoplásicos/química , Antineoplásicos/efeitos da radiação , Células Hep G2 , Humanos , Hipertermia Induzida/métodos , Raios Infravermelhos , Camundongos , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Nanopartículas/química , Nanopartículas/efeitos da radiação , Compostos de Organossilício/química , Compostos de Organossilício/efeitos da radiação , Técnicas Fotoacústicas/métodos , Polímeros/química , Polímeros/efeitos da radiação , Nanomedicina Teranóstica/métodos , Tiadiazóis/química , Tiadiazóis/efeitos da radiação
11.
J Mater Chem B ; 7(42): 6576-6584, 2019 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-31588950

RESUMO

NIR-II fluorescence imaging has great potential in diagnosis, but the quantum efficiency of contrast agents is an urgent problem to be solved. We synthesized two new multifunctional polymers, P-TT and P-DPP, with a tetrahedral C (sp3) and branched alkyl chains in the main chain, which were beneficial to obtain high quantum efficiency. P-TT and P-DPP showed absorption peaks of 686 nm and 763 nm, respectively, and fluorescence emission peaks of 1071 nm and 1066 nm, respectively. The photothermal effect of P-DPP can reach 52 °C, and the quantum yield reaches 1.5%, which was three times higher than that of nanotube fluorophores (quantum yield 0.4%). P-DPP is used for stable fluorescence imaging of blood vessels and photoacoustic imaging of nude mice, and successfully applied to phototherapy of nude mouse tumours.


Assuntos
Antineoplásicos/uso terapêutico , Nanopartículas/uso terapêutico , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Polímeros/uso terapêutico , Tiofenos/uso terapêutico , Animais , Antineoplásicos/síntese química , Antineoplásicos/efeitos da radiação , Antineoplásicos/toxicidade , Feminino , Corantes Fluorescentes , Células HeLa , Humanos , Hipertermia Induzida/métodos , Raios Infravermelhos , Fígado/diagnóstico por imagem , Camundongos Nus , Nanopartículas/efeitos da radiação , Nanopartículas/toxicidade , Técnicas Fotoacústicas/métodos , Fotoquimioterapia/métodos , Polímeros/síntese química , Polímeros/efeitos da radiação , Polímeros/toxicidade , Tiofenos/síntese química , Tiofenos/efeitos da radiação , Tiofenos/toxicidade , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Nanomedicine ; 21: 102042, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31247311

RESUMO

Targeted, biocompatible, and synergistic "all in one" systems should be designed to combat the heterogeneity of cancer. In this study, we constructed a dual function nanosystem, copper sulfide nanoplatform loaded with the chemotherapeutic drug docetaxel wrapped by a conjugated polymer-peptide for targeted chemo-phototherapy. The nanoconstruct has been successfully designed with a size of 186.1 ±â€¯5.2 nm, a polydispersity index of 0.18 ±â€¯0.01, and zeta potential of -16.4 ±â€¯0.1 mV. The enhanced uptake and near-infrared-responsive behavior of the nanosystem resulted in efficient drug release, photothermal ablation, effective cytotoxic activity, and potentiated reactive oxygen species generation. The induction of apoptotic markers, enhanced accumulation in the tumor site, and maximum tumor growth inhibition were seen during in vivo studies compared to non-targeted nanoformulations and free drug. Cumulatively, our results indicate that, with low systemic toxicity and better biocompatibility, this nanoconstruct could provide a promising strategy for treating prostate cancer.


Assuntos
Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Polímeros/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/efeitos da radiação , Proliferação de Células/efeitos dos fármacos , Cobre/química , Doxorrubicina/química , Liberação Controlada de Fármacos/efeitos da radiação , Humanos , Hipertermia Induzida , Masculino , Nanopartículas/química , Peptídeos/química , Peptídeos/farmacologia , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Fototerapia , Polímeros/química , Polímeros/efeitos da radiação , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Espécies Reativas de Oxigênio/química , Receptores de Somatostatina/genética , Somatostatina/análogos & derivados , Somatostatina/química , Somatostatina/farmacologia , Sulfetos/química
14.
Nat Commun ; 10(1): 1192, 2019 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-30867429

RESUMO

Development of photothermal materials which are able to harness sunlight and convert it to thermal energy seems attractive. Besides carbon-based nanomaterials, conjugated polymers are emerging promising photothermal materials but their facile syntheses remain challenging. In this work, by modification of a CBT-Cys click condensation reaction and rational design of the starting materials, we facilely synthesize conjugated polymers poly-2-phenyl-benzobisthiazole (PPBBT) and its dihexyl derivative with good photothermal properties. Under the irradiation of either sunlight-mimicking Xe light or near-infrared laser, we verify that PPBBT has comparable photothermal heating-up speed to that of star material single-wall carbon nanotube. Moreover, PPBBT is used to fabricate water-soluble NPPPBBT nanoparticles which maintain excellent photothermal properties in vitro and photothermal therapy effect on the tumours exposed to laser irradiation. We envision that our synthetic method provides a facile approach to fabricate conjugated polymers for more promising applications in biomedicine or photovoltaics in the near future.


Assuntos
Hipertermia Induzida/métodos , Nanopartículas/efeitos da radiação , Neoplasias/terapia , Nanomedicina Teranóstica/métodos , Terapia Ultravioleta/métodos , Animais , Linhagem Celular Tumoral/transplante , Terapia Combinada/métodos , Modelos Animais de Doenças , Feminino , Humanos , Hipertermia Induzida/instrumentação , Lasers , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Transmissão , Nanopartículas/administração & dosagem , Nanopartículas/química , Nanopartículas/ultraestrutura , Polímeros/administração & dosagem , Polímeros/química , Polímeros/farmacocinética , Polímeros/efeitos da radiação , Distribuição Tecidual , Resultado do Tratamento , Terapia Ultravioleta/instrumentação
15.
Chembiochem ; 20(13): 1628-1636, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30690811

RESUMO

In recent years, semiconducting polymer nanoparticles (SPNs) have been attracting considerable attention because of their outstanding characteristics such as higher light and thermal stability. They are widely used in fields of biomedicine such as photoacoustic (PA) imaging (PAI), photodynamic therapy (PDT), and photothermal therapy (PTT). PAI, a new imaging modality based on PA effects, shows great promise in biomedical applications. SPNs that display strong optical absorbance in the visible and near-infrared (NIR) regions can be promising candidates for in vivo PTT and PAI. Here we introduce the preparation of organic conjugated polymer fluorescent nanoparticles in the aqueous phase. We then discuss the application of water-dispersible conjugated polymer nanoparticles in PA and PTT. Finally, we discuss the opportunities and challenges for the development of organic conjugated polymer nanoparticles.


Assuntos
Antineoplásicos/uso terapêutico , Nanopartículas/uso terapêutico , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Polímeros/uso terapêutico , Semicondutores , Animais , Antineoplásicos/química , Antineoplásicos/efeitos da radiação , Humanos , Hipertermia Induzida/métodos , Luz , Nanopartículas/química , Nanopartículas/efeitos da radiação , Imagem Óptica/métodos , Técnicas Fotoacústicas/métodos , Fototerapia/métodos , Polímeros/química , Polímeros/efeitos da radiação
16.
J Mater Chem B ; 7(13): 2190-2200, 2019 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-32073578

RESUMO

Cancer cells possess some inherent characteristics, such as glucose-dependence and intolerance to heat and exogenous reactive oxygen species (ROS). In this study, a strategy has been developed to target these vulnerable weaknesses of cancer cells using glucose oxidase (GOx) and polydopamine (PDA) functionalized iron oxide nanoparticles (Fe3O4@PDA/GOx NPs). PDA is first deposited on the surfaces of iron oxide NPs through self-polymerization, and then GOx is covalently linked with PDA upon mixing the enzyme and Fe3O4@PDA under alkaline conditions. In this system, the PDA layer along with iron oxide NPs serves as a photothermal transfer material converting near infrared (NIR) radiation into heat. The covalently linked GOx can competitively consume glucose and spontaneously generate ROS H2O2 that can be further converted by the iron oxide NPs into more toxic ˙OH, inducing apoptosis of cancer cells. The selective toxicity of Fe3O4@PDA/GOx NPs on cancer cells is demonstrated both in vitro and in vivo. In particular, a single injection rather than multiple doses results in significant suppression of tumors, and does not induce apparent histological lesions in the 4T1 tumor-bearing Balb/c mice. The versatility of the functionalization strategy reported in this study will contribute to developing efficient therapies for selective cancer treatment.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Glucose Oxidase/uso terapêutico , Peróxido de Hidrogênio/metabolismo , Indóis/uso terapêutico , Nanopartículas de Magnetita/uso terapêutico , Polímeros/uso terapêutico , Animais , Antineoplásicos/química , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Dano ao DNA/efeitos dos fármacos , Enzimas Imobilizadas/química , Enzimas Imobilizadas/uso terapêutico , Enzimas Imobilizadas/toxicidade , Glucose Oxidase/química , Glucose Oxidase/toxicidade , Humanos , Hipertermia Induzida/métodos , Indóis/química , Indóis/efeitos da radiação , Indóis/toxicidade , Raios Infravermelhos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/toxicidade , Camundongos Endogâmicos BALB C , Fototerapia/métodos , Polímeros/química , Polímeros/efeitos da radiação , Polímeros/toxicidade , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Carbohydr Polym ; 205: 533-539, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30446137

RESUMO

Bacterial biofilms are widely associated with persistent infections and food contamination. High resistance to conventional antimicrobial agents resulted in an urgent need for novel formulation to eliminate these bacterial communities. Herein we fabricated light controllable chitosan micelles loading with thymol (T-TCP) for elimination of biofilm. Due to the exterior chitosan, T-TCP micelles easily bind to negative biofilm through electrostatic interaction and efficiently deliver the essential oil payloads. Under irradiation, T-TCP micelles generated ROS, which triggered simultaneous thymol release and also resulted in additional ROS-inducing bactericidal effects, both effectively eradicating biofilms of Listeria monocytogenes and Staphylococcus aureus. This formulation provided a platform for other water-insoluble antimicrobials and might be used as a potent and controllable solution to biofilm fighting.


Assuntos
Biofilmes/efeitos dos fármacos , Quitosana/análogos & derivados , Quitosana/química , Portadores de Fármacos/química , Micelas , Timol/farmacologia , Quitosana/síntese química , Quitosana/efeitos da radiação , Portadores de Fármacos/síntese química , Portadores de Fármacos/efeitos da radiação , Liberação Controlada de Fármacos/efeitos da radiação , Interações Hidrofóbicas e Hidrofílicas , Luz , Listeria monocytogenes/fisiologia , Óleos Voláteis/farmacologia , Polímeros/síntese química , Polímeros/química , Polímeros/efeitos da radiação , Espécies Reativas de Oxigênio , Staphylococcus aureus/fisiologia , Sulfetos/síntese química , Sulfetos/química , Sulfetos/efeitos da radiação , Cloreto de Tolônio/síntese química , Cloreto de Tolônio/química , Cloreto de Tolônio/efeitos da radiação
18.
Chem Commun (Camb) ; 54(96): 13599-13602, 2018 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-30451251

RESUMO

We designed novel diketopyrrolopyrrole polymer based nanoparticles (DPP-IID-FA), which exhibited strong light absorption and excellent photothermal conversion in the NIR optical window, and displayed high biocompatibility and photostability. Furthermore, our nanoparticles could be efficiently uptaken by cancer cells and exhibited outstanding anticancer ability both in vitro and in vivo under NIR-II laser irradiation.


Assuntos
Antineoplásicos/uso terapêutico , Nanopartículas/química , Polímeros/uso terapêutico , Pirróis/uso terapêutico , Neoplasias do Colo do Útero/terapia , Animais , Antineoplásicos/síntese química , Antineoplásicos/efeitos da radiação , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Células HeLa , Calefação , Humanos , Raios Infravermelhos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/efeitos da radiação , Fototerapia/métodos , Polímeros/síntese química , Polímeros/efeitos da radiação , Polímeros/toxicidade , Pirróis/síntese química , Pirróis/efeitos da radiação , Pirróis/toxicidade
19.
Theranostics ; 8(15): 4097-4115, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30128039

RESUMO

Chemo-photothermal therapy shows great potential for inhibiting tumor growth. However, achieving maximal chemo-photothermal synergistic efficacy is challenging because of the low efficiency of controllable chemo-drug release in response to external or internal triggers. Thus, a nano-delivery system that could effectively achieve photothermal therapy and dual stimuli-responsive (heat and pH) drug release to inhibit both primary breast tumor growth and metastases is required. Methods: Herein, a thermo- and pH-responsive polymer (mPEG-PAAV) with an upper critical solution temperature (UCST) was synthesized to fabricate a DOX- and IR780-loaded micellar system. After systematic studies of the photothermal performance and controllable drug release of mPEG-PAAV micelles/IR780+DOX under NIR irradiation at different pH values, their chemo-photothermal synergetic therapy efficacies were also estimated both in in vitro and in vivo. Results: Because of the photothermal conversion of mPEG-PAAV micelle/IR780+DOX (~200 nm, 3.82 mV), high local temperature could be induced at the tumor site under NIR laser irradiation. This hyperthermia not only produced an enhanced tumor necrosis, but also broke down the micelles under the decreased pH environment, resulting in rapid DOX release and enhanced intracellular drug accumulation after NIR laser irradiation. In addition, photoacoustic imaging (PAI) of mPEG-PAAV/IR780+DOX micelle was adopted to monitor the morphology and micro-vascular distribution of the tumor tissue, which could also guide the chemo-photothermal therapy. Most importantly, the systemic administration of mPEG-PAAV micelles/IR780+DOX combined with NIR laser irradiation could simultaneously eliminate the 4T1 breast tumor and thoroughly suppress lung metastasis without any obvious adverse effects. Conclusion: Herein, a pH- and thermo-dual responsive UCST micelle system was developed for delivering IR780 and DOX, which could achieve NIR laser-controlled drug release and PA imaging guidance for chemo-photothermal synergistic therapy of both primary breast tumors and their metastases.


Assuntos
Neoplasias da Mama/terapia , Portadores de Fármacos/administração & dosagem , Tratamento Farmacológico/métodos , Hipertermia Induzida/métodos , Nanoestruturas/administração & dosagem , Técnicas Fotoacústicas/métodos , Fototerapia/métodos , Animais , Neoplasias da Mama/secundário , Terapia Combinada/métodos , Modelos Animais de Doenças , Doxorrubicina/administração & dosagem , Portadores de Fármacos/efeitos da radiação , Concentração de Íons de Hidrogênio , Indóis/administração & dosagem , Raios Infravermelhos , Camundongos Endogâmicos BALB C , Micelas , Nanoestruturas/efeitos da radiação , Polímeros/administração & dosagem , Polímeros/efeitos da radiação , Temperatura
20.
Phys Med Biol ; 63(6): 06NT01, 2018 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-29528035

RESUMO

Recent developments in radiation therapy aimed at more precise dose delivery along with higher dose gradients (dose painting) and more efficient dose delivery with higher dose rates e.g. flattening filter free (FFF) irradiation. Magnetic-resonance-imaging based polymer gel dosimetry offers 3D information for precise dose delivery techniques. Many of the proposed polymer gels have been reported to exhibit a dose response, measured as relaxation rate ΔR2(D), which is dose rate dependent. A lack of or a reduced dose-rate sensitivity is very important for dosimetric accuracy, especially with regard to the increasing clinical use of FFF irradiation protocols with LINACs at high dose rates. Some commonly used polymer gels are based on Methacrylic-Acid-Gel-Initiated-by-Copper (MAGIC). Here, we report on the dose sensitivity (ΔR2/ΔD) of MAGIC-type gels with different oxygen scavenger concentration for their specific dependence on the applied dose rate in order to improve the dosimetric performance, especially for high dose rates. A preclinical x-ray machine ('Yxlon', E = 200 kV) was used for irradiation to cover a range of dose rates from low [Formula: see text] min = 0.6 Gy min-1 to high [Formula: see text] max = 18 Gy min-1. The dose response was evaluated using R2-imaging of the gel on a human high-field (7T) MR-scanner. The results indicate that all of the investigated dose rates had an impact on the dose response in polymer gel dosimeters, being strongest in the high dose region and less effective for low dose levels. The absolute dose rate dependence [Formula: see text] of the dose response in MAGIC-type gel is significantly reduced using higher concentrations of oxygen scavenger at the expense of reduced dose sensitivity. For quantitative dose evaluations the relative dose rate dependence of a polymer gel, normalized to its sensitivity is important. Based on this normalized sensitivity the dose rate sensitivity was reduced distinctly using an increased oxygen scavenger concentration with reference to standard MAGIC-type gel formulation at high dose rate levels. The proposed gel composition with high oxygen scavenger concentration exhibits a larger linear active dose response and might be used especially in FFF-radiation applications and preclinical dosimetry at high dose rates. We propose in general to use high dose rates for calibration and evaluation as the change in relative dose sensitivity is reduced at higher dose rates in all of the investigated gel types.


Assuntos
Ácido Ascórbico/química , Sulfato de Cobre/química , Sequestradores de Radicais Livres/química , Gelatina/química , Hidroquinonas/química , Imageamento por Ressonância Magnética/métodos , Metacrilatos/química , Oxigênio/química , Polímeros/química , Radiometria/métodos , Ácido Ascórbico/efeitos da radiação , Calibragem , Sulfato de Cobre/efeitos da radiação , Gelatina/efeitos da radiação , Humanos , Hidroquinonas/efeitos da radiação , Metacrilatos/efeitos da radiação , Polímeros/efeitos da radiação , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador
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