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1.
Mater Today Bio ; 21: 100729, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37529216

RESUMO

Infectious disease is one of the top 10 causes of death worldwide, especially in low-income countries. The extensive use of antibiotics has led to an increase in antibiotic resistance, which poses a critical threat to human health globally. Natural products such as polyphenolic compounds and their derivatives have been shown the positive therapeutic effects in antibacterial therapy. However, the inherent physicochemical properties of polyphenolic compounds and their derivatives limit their pharmaceutical effects, such as short half-lives, chemical instability, low bioavailability, and poor water solubility. Nanoformulations have shown promising advantages in improving antibacterial activity by controlling the release of drugs and enhancing the bioavailability of polyphenols. In this review, we listed the classification and antibacterial mechanisms of the polyphenolic compounds. More importantly, the nanoformulations for the delivery of polyphenols as the antibacterial agent were summarized, including different types of nanoparticles (NPs) such as polymer-based NPs, metal-based NPs, lipid-based NPs, and nanoscaffolds such as nanogels, nanofibers, and nanoemulsions. At the same time, we also presented the potential biological applications of the nano-system to enhance the antibacterial ability of polyphenols, aiming to provide a new therapeutic perspective for the antibiotic-free treatment of infectious diseases.

2.
Int J Mol Sci ; 24(5)2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36901762

RESUMO

Respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are critical areas of medical research, as millions of people are affected worldwide. In fact, more than 9 million deaths worldwide were associated with respiratory diseases in 2016, equivalent to 15% of global deaths, and the prevalence is increasing every year as the population ages. Due to inadequate treatment options, the treatments for many respiratory diseases are limited to relieving symptoms rather than curing the disease. Therefore, new therapeutic strategies for respiratory diseases are urgently needed. Poly (lactic-co-glycolic acid) micro/nanoparticles (PLGA M/NPs) have good biocompatibility, biodegradability and unique physical and chemical properties, making them one of the most popular and effective drug delivery polymers. In this review, we summarized the synthesis and modification methods of PLGA M/NPs and their applications in the treatment of respiratory diseases (asthma, COPD, cystic fibrosis (CF), etc.) and also discussed the research progress and current research status of PLGA M/NPs in respiratory diseases. It was concluded that PLGA M/NPs are the promising drug delivery vehicles for the treatment of respiratory diseases due to their advantages of low toxicity, high bioavailability, high drug loading capacity, plasticity and modifiability. And at the end, we presented an outlook on future research directions, aiming to provide some new ideas for future research directions and hopefully to promote their widespread application in clinical treatment.


Assuntos
Asma , Nanopartículas , Doença Pulmonar Obstrutiva Crônica , Transtornos Respiratórios , Doenças Respiratórias , Humanos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Ácido Poliglicólico/química , Ácido Láctico/química , Nanopartículas/química , Portadores de Fármacos/química
3.
Molecules ; 29(1)2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38202616

RESUMO

Chitosan nanoparticles (NPs) serve as useful multidrug delivery carriers in cancer chemotherapy. Chitosan has considerable potential in drug delivery systems (DDSs) for targeting tumor cells. Doxorubicin (DOX) has limited application due to its resistance and lack of specificity. Chitosan NPs have been used for DOX delivery because of their biocompatibility, biodegradability, drug encapsulation efficiency, and target specificity. In this review, various types of chitosan derivatives are discussed in DDSs to enhance the effectiveness of cancer treatments. Modified chitosan-DOX NP drug deliveries with other compounds also increase the penetration and efficiency of DOX against tumor cells. We also highlight the endogenous stimuli (pH, redox, enzyme) and exogenous stimuli (light, magnetic, ultrasound), and their positive effect on DOX drug delivery via chitosan NPs. Our study sheds light on the importance of chitosan NPs for DOX drug delivery in cancer treatment and may inspire the development of more effective approaches for cancer chemotherapy.


Assuntos
Quitosana , Nanopartículas , Neoplasias , Humanos , Sistemas de Liberação de Medicamentos , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Neoplasias/tratamento farmacológico
4.
Adv Mater ; 34(50): e2206851, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36193764

RESUMO

Currently, immune checkpoint therapy combined with chemotherapy and radiotherapy is a useful strategy for improving immunotherapy's therapeutic efficacy. However, chemotherapy and radiotherapy cause serious side effects, so finding safe and effective methods to combine with immunotherapy is critical. In this work, regulating tumor glycometabolism is found to induce tumor cell pyroptosis and regulate the degree of expression of programmed death-ligand 1 (PD-L1). Therefore, how to treat tumors by regulating tumor glycometabolism in combination with anti-PD-L1 therapy is investigated here. First, the biomineralization-like method is used to construct nanoparticles with two-enzymatic activity by hybridizing nanozymes and glucose oxidase (GOx). It has the ability to self-amplify regulation of the glycometabolism of tumor cells. It can also induce tumor cell pyroptosis and increase the expression of PD-L1 in tumor cells. To treat tumors, nanoparticles are further combined with anti-PD-L1, which substantially inhibits tumor development and significantly increases  the survival time of mice. Combination therapy also has a significant immunological memory effect, successfully preventing tumor recurrence and metastasis. This is thought to be the first study that combines tumor glycometabolism with immunocheckpoint blocking in cancer therapy. This innovative, safe, low-toxic, and highly effective anti-tumor strategy can have good prospects in clinical applications.


Assuntos
Nanopartículas , Neoplasias , Camundongos , Animais , Piroptose , Imunoterapia/métodos , Neoplasias/terapia , Terapia Combinada , Linhagem Celular Tumoral , Microambiente Tumoral
5.
Biomaterials ; 289: 121794, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36113330

RESUMO

As a representative of tumor immunotherapy, tumor vaccine can inhibit tumor growth by activating tumor-specific immune response, which has the advantages of relatively low toxicity and high efficiency, and has attracted much attention in recent years. However, there are still difficulties in how to effectively deliver tumor vaccines in vivo and make them work efficiently. It is a relatively mature method to load tumor specific antigens with suitable carriers to produce tumor vaccines. Here, a generally minimalist construction method of tumor nanovaccine was developed. A high-efficiency tumor nanovaccine (NV) was prepared in one step by a biomineralization-like method, which contained ovalbumin (OVA, model antigen), unmethylated cytosine-phosphate-guanine (CpG, adjuvant) and Mn-NP (carrier and adjuvant). NV not only showed good tumor preventive effect, but also could successfully inhibited tumor development and metastasis when combined with anti-PD-L1, and induced long-term immune memory effect. However, the method of screening tumor specific antigen to construct nanovaccine is cumbersome and tumors are heterogeneous. Therefore, surgically resected tumor tissue is the best source of antigens for preparing tumor vaccines. Next, based on the strong loading ability of the carrier, we designed a personalized tumor nanovaccine (PNV) using the supernatant of tumor abrasive fluid (STAF) as antigen based on the generally minimalist tumor nanovaccine construction strategy. PNV combined with anti-PD-L1 could successfully inhibit post-surgical tumor recurrence and induce strong and durable immune memory effects. This study presents a novel, general, and minimalist strategy to construct high-efficiency personalized nanovaccine, which has a wide range of potential applications in the field of tumor treatment.


Assuntos
Vacinas Anticâncer , Nanopartículas , Neoplasias , Animais , Antígenos de Neoplasias , Citosina , Guanina , Humanos , Inibidores de Checkpoint Imunológico , Imunoterapia/métodos , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias/terapia , Ovalbumina , Fosfatos
6.
Acta Biomater ; 144: 132-141, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35307591

RESUMO

Because of molecular heterogeneity in tumors, clinical outcomes of tumor treatment are not very satisfactory, and novel strategies are therefore needed to address this challenge. Combination therapy could efficiently enhance tumor treatment by stimulating multiple pathways, reducing the systemic toxicity of monotherapy, and regulating the tumor immune microenvironments. Herein, metal-organic framework MIL-100 (Fe) nanoparticles (NPs) were synthesized by a microwave-assisted method, and oxaliplatin (OXA) and indocyanine green (ICG) were then loaded into hyaluronic acid (HA)-modified MIL-100 NPs to obtain multifunctional nanoparticles (OIMH NPs). The OIMH NPs exhibited sensitive photoacoustic imaging (PAI) for imaging-guided therapy and showed a good synergistic effect by combining chemotherapy with photothermal therapy (PTT) to kill tumor cells. Immunogenic cell death (ICD) and activation of T cells induced by the chemo-photothermal therapy could sensitize for immune checkpoint blockade (aPD-L1) response, thus eliciting systemic antitumor immunity. Finally, tumor inhibition was observed, which could be attributed to the combination of chemotherapy, PTT, and aPD-L1. On the basis of the study findings, an innovative imaging-mediated combined therapeutic strategy involving multifunctional NPs was proposed, which might potentially offer a new clinical treatment for colorectal cancer. STATEMENT OF SIGNIFICANCE: The metal-organic framework-mediated chemo-photothermal therapy guided by photoacoustic imaging (PAI) is an accurate and effective approach for tumor inhibition, which can synergistically achieve immunogenic cell death and lead to an increasing infiltration of immune cells in the tumor microenvironment, thereby enhancing the sensitivity for immune checkpoint blockade (aPD-L1) therapy. This type of therapy can not only reduce the systemic toxicity caused by traditional treatment methods, but it can also solve the issue of low response of immune checkpoint blockade in colorectal cancer (CRC). Our study provides experimental evidence for using the combination of immunotherapy and chemo-photothermal therapy against CRC.


Assuntos
Neoplasias Colorretais , Estruturas Metalorgânicas , Nanopartículas Multifuncionais , Nanopartículas , Linhagem Celular Tumoral , Neoplasias Colorretais/terapia , Humanos , Inibidores de Checkpoint Imunológico , Imunoterapia , Estruturas Metalorgânicas/farmacologia , Nanopartículas/uso terapêutico , Fototerapia , Terapia Fototérmica , Microambiente Tumoral
7.
Medicine (Baltimore) ; 100(14): e25469, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33832160

RESUMO

RATIONALE: Eccrine spiradenoma (ES) is a rare benign skin adnexal tumor originating from eccrine sweat glands. The features of ES on ultrasonography (US) have received little attention. Therefore, we report the sonographic findings in a case of an ES that originated from the abdominal wall and discuss the previously reported cases. PATIENT CONCERNS: A 53-year-old woman was admitted to our hospital with a complaint of a painful nodule on the right side of her abdominal wall of 1-year duration. DIAGNOSES: The mass on the right side of abdominal wall was diagnosed as ES by histopathological examination. INTERVENTIONS: The patient subsequently underwent total excision of the mass. OUTCOMES: The patient recovered well and had no complications during the 1-year follow-up. LESSONS: As eccrine spiradenoma (ES) is rare and most of the tumors are excised without prior imaging studies. Little is known regarding the features of ES on ultrasonography (US). Familiarizing with the clinical and US features of this rare tumor may increase awareness of the disease among sonographers and clinicians.


Assuntos
Acrospiroma/diagnóstico por imagem , Neoplasias das Glândulas Sudoríparas/diagnóstico por imagem , Ultrassonografia Doppler em Cores , Feminino , Humanos , Pessoa de Meia-Idade
8.
Biomaterials ; 264: 120382, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32971373

RESUMO

Developing an ideal photothermal agent is one of the challenges for effective photothermal therapy (PTT). Herein, a green and simple yet versatile method is developed to construct a novel poly-(iron-dopamine coordination complexes) nanoparticles (P[Fe-DA]-NPs) based on polymerization and coordination synergistically by using Fe3+ ions and dopamine (DA) in aqueous solution, and simultaneously poly(vinylpyrrolidone) (PVP) is applied to improve dispersion stability. P[Fe-DA]-NPs can be laden into macrophages directly with no further purification required to target tumor tissue to perform cell-mediated strategy. P[Fe-DA]-laden macrophages as an ideal photothermal agent has the advantages of good biocompatibility, simple preparation process, high photothermal performance, and effective tumor targeting. Furthermore, the P[Fe-DA]-laden macrophages possess excellent photoacoustic imaging (PAI) capacity for guiding the precise PTT. The results show that the tumors are significantly suppressed after PTT with the help of the accurate PAI diagnosis. This cell-mediated strategy may be the most promising avenue for the future clinical cancer therapy.


Assuntos
Nanopartículas , Neoplasias , Técnicas Fotoacústicas , Humanos , Macrófagos , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Fototerapia , Polimerização
9.
Macromol Biosci ; 21(1): e2000192, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33043592

RESUMO

Despite the polymeric vascular disrupting agent (poly(L -glutamic acid)-graft-methoxy poly(ethylene glycol)/combretastatin A4) nanoparticles can efficiently inhibit cancer growth, their further application is still a challenge owing to the tumor recurrence and metastasis after treatment. In this study, two poly(L -glutamic acid)-drug conjugates for chemo-and photodynamic combination therapy are fabricated. PLG-g-mPEG-CA4 nanoparticles are prepared by combretastatin A4 (CA4) and poly(L -glutamic acid)-graft-methoxy poly(ethylene glycol) (PLG-g-mPEG) using the Yamaguchi esterification reaction. PLG-g-mPEG-TPP (TPP: 5, 10, 15, 20-tetraphenylporphyrin) nanoparticles are constructed using PLG-g-mPEG and amine porphyrin through condensation reaction between carboxyl group of PLG-g-mPEG and amino group of porphyrin. The results showed that PLG-g-mPEG-CA4 nanoparticles have good antitumor ability. PLG-g-mPEG-TPP nanoparticles can produce singlet oxygen under the laser irradiation. Moreover, the combined therapy of PLG-g-mPEG-CA4 and PLG-g-mPEG-TPP nanoparticles has higher antitumor effect than the single chemotherapy or the single photodynamic therapy in vitro. The combination of CA4 nondrug and photodynamic therapy provides a new insight for enhancing the tumor therapeutic effect with vascular disrupting agents and other therapy.


Assuntos
Proliferação de Células/efeitos dos fármacos , Nanopartículas/química , Neoplasias/tratamento farmacológico , Fotoquimioterapia , Animais , Sobrevivência Celular/efeitos dos fármacos , Humanos , Camundongos , Neoplasias/patologia , Oxigênio/química , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Ácido Poliglutâmico/química , Ácido Poliglutâmico/farmacologia , Estilbenos/química , Estilbenos/farmacologia
10.
Sci Adv ; 6(40)2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32998884

RESUMO

Immune checkpoint blockade therapy (ICT) has shown potential in the treatment of multiple tumors, but suffers poor response rate in clinic. We found that even combining ICT with chemotherapy, which was wildly used in clinical trials, failed to achieve satisfactory tumor inhibition in the B16F10 model. Thus, we further constructed a previously unexplored immune cocktail therapy and realized multiple boosting of the cancer-immunity cycle. Cocktail therapy consisted of two kinds of tumor microenvironment-responsive drug and gene delivery nanoparticles to achieve specific delivery of doxorubicin and codelivery of plasmids expressed small hairpin RNA of PD-L1 (pshPD-L1) and hyaluronidase (pSpam1) in the tumor area. Experimental evidences proved that any component in the cocktail therapy was indispensable, and the cocktail therapy exhibited excellent antitumor effects against different types of tumors. The cocktail therapy presented here offers a searching strategy for more synergistic units with ICT and is meaningful for developing more efficient antitumor immunotherapy.

11.
J Control Release ; 328: 631-639, 2020 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-32950593

RESUMO

Numerous biological enzymes are considered promising for tumor therapy. However, the remote control of enzymatic activity in vivo to achieve a satisfactory therapeutic effect remains challenge. Herein, we loaded chlorin e6 (Ce6) to the peroxidase-mimic metal-organic framework (MOF) MIL-100 (Ce6@MIL-100) to develop cascade-reaction nanoparticles shielded with hyaluronic acid (CMH NPs). CMH NPs and the highly expressed H2O2 in the tumor site underwent Fenton reaction to generate hydroxyl radical (·OH) and O2. The produced ·OH and O2 were used for chemodynamic therapy and alleviating hypoxia, respectively. Under near-infrared light irradiation, the Ce6-mediated photochemical effect not only generated cytotoxic singlet oxygen (1O2) for enhanced photodynamic therapy with additional oxygen supply, but also produced H2O2 to amplify the Fenton reaction. Therefore, the CMH NPs exhibited a virtuous cycle of cascade reactions. Furthermore, comprehensive experiments demonstrated that combined therapy could effectively ablate tumors. Thus, the nanozyme based on MOF realized potent chemo-photodynamic therapeutic efficacy. Overall, the nanoplatform displayed an exciting biomedical application of MOF-derived nanozyme as a versatile therapeutic agent.


Assuntos
Estruturas Metalorgânicas , Nanopartículas , Neoplasias , Fotoquimioterapia , Porfirinas , Linhagem Celular Tumoral , Humanos , Peróxido de Hidrogênio , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/uso terapêutico
12.
ACS Appl Mater Interfaces ; 12(17): 19295-19306, 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32239907

RESUMO

Recently, pH-sensitive polymers have received extensive attention in tumor therapy. However, the rapid response to pH changes is the key to achieving efficient treatment. Here, a novel shielding system with a rapidly pH-responsive polymer (PAMT) is synthesized by click reaction between poly(γ-allyl-l-glutamate) and thioglycolic acid or 2-(Boc-amino)ethanethiol. The zwitterionic biodegradable polymer PAMT, which is negatively charged at physiological pH, can be used to shield positively charged nanoparticles. PAMT is electrostatically attached to the surface of the positively charged PEI/pDNA complex to form a ternary complex. The zwitterionic PAMT-shielded complex exhibits rapid charge conversion when the pH decreases from 7.4 to 6.8. For the in vivo tumor inhibition experiment, PAMT/PEI/shVEGF injected intravenously shows a more significant inhibitory effect on tumor growth. The excellent results are mainly attributed to introduction of the zwitterionic copolymer PAMT, which can shield the positively charged PEI/shVEGF complex in physiological conditions, while the surface potential of the shielded complexes changes to a positive charge in the acidic tumor environment.


Assuntos
DNA/uso terapêutico , Portadores de Fármacos/química , Neoplasias/terapia , Plasmídeos/uso terapêutico , Ácido Poliglutâmico/análogos & derivados , Animais , Linhagem Celular Tumoral , DNA/genética , DNA/toxicidade , Portadores de Fármacos/síntese química , Portadores de Fármacos/toxicidade , Técnicas de Transferência de Genes , Terapia Genética/métodos , Concentração de Íons de Hidrogênio , Masculino , Camundongos Endogâmicos BALB C , Plasmídeos/genética , Plasmídeos/toxicidade , Polietilenoimina/química , Polietilenoimina/toxicidade , Ácido Poliglutâmico/síntese química , Ácido Poliglutâmico/toxicidade , RNA Antissenso/genética , Fator A de Crescimento do Endotélio Vascular/genética , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Nanoscale ; 12(3): 1349-1355, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31913380

RESUMO

Nowadays, Fenton reaction-based chemodynamic therapy (CDT) strategies have drawn extensive attention as tumor-specific nanomedicine-based therapy. Nevertheless, current existing CDTs normally suffer from therapeutic bottlenecks such as the scavenging of hydroxyl radical (˙OH) by intracellular antioxidants and unideal therapeutic outcome of single treatment modality. Herein, we constructed novel all-in-one AFP nanoparticles (NPs) as CDT agents through a one-pot process for multifunctional nanotheranostics. The as-constructed AFP NPs could simultaneously produce ˙OH through the Fenton reaction and scavenge intracellular glutathione, functioning as self-reinforced CDT agents to achieve tumor-triggered enhanced CDT (ECDT). In addition, the AFP NPs possessed the capability of H2O2 and acid-boosted photoacoustic imaging and photothermal therapy, enabling a precise and effective tumor therapeutic outcome with minimal nonspecific damage in combination with ECDT. Our novel nanoplatform would open new perspectives on multi-functional CDT agents for accurate and non-invasive tumor theranostics.


Assuntos
Glutationa/metabolismo , Hipertermia Induzida , Nanopartículas , Neoplasias Experimentais , Técnicas Fotoacústicas , Fototerapia , Animais , Linhagem Celular Tumoral , Humanos , Camundongos , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/terapia , Nanomedicina Teranóstica
14.
Biomaterials ; 223: 119470, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31526950

RESUMO

Nowadays, two-dimensional (2D) nanomaterials with many fascinating physicochemical properties have drawn extensive attention as drug delivery platforms for cancer theranostics. Nevertheless, current existing 2D nanomaterial-based drug delivery systems normally undergo the bottlenecks of hash preparation process, low drug loading content and unsatisfactory therapeutic outcome. Herein, we developed a novel nanoparticles-induced assemble strategy to construct 2D nanosheets with ultra-high curcumin loading content of 59.6 % and excellent stability in water. Furthermore, a distinct photothermal effect and multimodal imaging property after polydopamine coating could be obtained, thereby leading to precise and efficient ablation of tumor in combination of curcumin-induced chemotherapy. More importantly, the design principle of our work offers novel facile strategy to assemble metal-binding drugs into 2D nanomedicine with high drug content and well-defined shapes.


Assuntos
Curcumina/química , Nanopartículas/química , Neoplasias/terapia , Fototerapia/métodos , Animais , Sistemas de Liberação de Medicamentos , Células HeLa , Humanos , Hipertermia Induzida , Indóis/química , Células MCF-7 , Metais/química , Camundongos , Microscopia Confocal , Imagem Multimodal , Nanomedicina , Transplante de Neoplasias , Polímeros/química , Ligação Proteica , Nanomedicina Teranóstica , Resultado do Tratamento , Água/química
15.
Biomater Sci ; 7(11): 4615-4623, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31441464

RESUMO

Doxorubicin (DOX) as a traditional chemotherapy drug is restricted in clinical applications due to its poor therapeutic activity and severe side effects. Herein, we prepared a metal-organic framework (MOF) MIL-100 by a microwave-assisted synthesis and DOX was loaded in MIL-100 and then, hyaluronic acid (HA) was modified on the surface of MIL-100 to give DMH NPs. The DMH NPs possessed the following advantages: (1) MIL-100 could serve as a drug carrier with a high DOX loading efficiency; MIL-100 could also generate a hydroxyl radical (˙OH) in the presence of H2O2 for chemodynamic therapy (CDT) via a Fenton-like reaction. (2) To improve the dispersibility of MIL-100, HA was modified on the surface of MIL-100, which could endow MIL-100 with a targeting ability towards tumor tissues. (3) DMH NPs could enhance antitumor efficacy and reduce drug-related toxicity though the combination of chemotherapy and chemodynamic therapy. DMH NPs have enormous potential as a candidate for reducing the systemic toxicity and improving the treatment effect for breast cancer.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/farmacologia , Estruturas Metalorgânicas/farmacologia , Nanopartículas/química , Animais , Antibióticos Antineoplásicos/química , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Doxorrubicina/química , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Liberação Controlada de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Células MCF-7 , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/patologia , Estruturas Metalorgânicas/química , Camundongos , Camundongos Endogâmicos BALB C , Imagem Óptica , Relação Estrutura-Atividade
16.
Adv Mater ; 31(40): e1902885, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31423690

RESUMO

Activatable theranostic agents that can be activated by tumor microenvironment possess higher specificity and sensitivity. Here, activatable nanozyme-mediated 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) loaded ABTS@MIL-100/poly(vinylpyrrolidine) (AMP) nanoreactors (NRs) are developed for imaging-guided combined tumor therapy. The as-constructed AMP NRs can be specifically activated by the tumor microenvironment through a nanozyme-mediated "two-step rocket-launching-like" process to turn on its photoacoustic imaging signal and photothermal therapy (PTT) function. In addition, simultaneously producing hydroxyl radicals in response to the high H2 O2 level of the tumor microenvironment and disrupting intracellular glutathione (GSH) endows the AMP NRs with the ability of enhanced chemodynamic therapy (ECDT), thereby leading to more efficient therapeutic outcome in combination with tumor-triggered PTT. More importantly, the H2 O2 -activated and acid-enhanced properties enable the AMP NRs to be specific to tumors, leaving the normal tissues unharmed. These remarkable features of AMP NRs may open a new avenue to explore nanozyme-involved nanoreactors for intelligent, accurate, and noninvasive cancer theranostics.


Assuntos
Materiais Biomiméticos/química , Peroxidases/metabolismo , Técnicas Fotoacústicas/métodos , Fototerapia/métodos , Nanomedicina Teranóstica/métodos , Microambiente Tumoral , Animais , Benzotiazóis/química , Terapia Combinada , Camundongos , Compostos Organometálicos/química , Povidona/química , Ácidos Sulfônicos/química
17.
Small ; 15(41): e1903016, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31423737

RESUMO

Developing tumor-responsive diagnosis and therapy strategies for tumor theranostics is still a challenge owing to their high accuracy and specificity. Herein, an AND logic gated-DNA nanodevice, based on the fluorescence nucleic acid probe and polymer-modified MnO2 nanosheets, for glutathione (GSH)-gated miRNA-21 signal amplification and GSH-activated magnetic resonance (MR) imaging-guided chemodynamic therapy (CDT) is reported. In the presence of overexpressed miRNA and GSH (tumor cells), the nanodevice can be in situ activated and release significantly amplified fluorescence signals and MR signals. Conversely, the fluorescence signal is quenched and MR signal remains at the background level with low miRNA and GSH (normal cells), efficiently reducing the false-positive signals by more than 50%. Under the guide of miRNA profiling and MR imaging, the tumor-responsive hydroxyl radical (·OH) can effectively kill tumor cells. Furthermore, the nanodevice shows catalase-like activity and glucose oxidase-like activity with the performance of O2 production and glucose consumption. This is the first time to fabricate a tumor-responsive theranostic DNA nanodevice with tumor-specific signal amplification of microRNA and GSH-activated MR imaging for CDT, potential hypoxia relief and starvation therapy, which provides a new insight for designing smart theranostic strategies.


Assuntos
DNA/metabolismo , Glutationa/metabolismo , Imageamento por Ressonância Magnética , MicroRNAs/metabolismo , Nanotecnologia/instrumentação , Neoplasias/genética , Nanomedicina Teranóstica , Animais , Células CHO , Catalase/metabolismo , Cricetinae , Cricetulus , Glucose Oxidase/metabolismo , Humanos , Peróxido de Hidrogênio/química , Ferro/química , Células MCF-7 , Compostos de Manganês/química , MicroRNAs/genética , Nanopartículas/química , Nanopartículas/ultraestrutura , Óxidos/química , Polietilenoimina/química
18.
Biomaterials ; 197: 284-293, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30677557

RESUMO

Despite multifunctional nanoparticles using for photothermal therapy can efficiently kill cancer cells, their further application is still hindered by the intrinsic high uptake in the reticuloendothelial system (RES) organs, causing the slow elimination from the body and potential toxicity to the body. Therefore, it is ideal to develop multifunctional nanoparticles which process the ability to effectively accumulate in tumors, while the nanoparticles can be rapidly excreted from the body via renal clearance after effective treatment. Herein, we report the multifunctional nanoparticles (FeTNPs) based on the coordination interaction of phenolic group and metal iron, which are composed of ferric iron, tannic acid (TA) and poly (glutamic acid)-graft-methoxypoly (ethylene glycol) (PLG-g-mPEG). FeTNPs exhibit the following highlighted features: (1) The effective accumulation in the tumor tissue is achieved based on EPR effect. (2) The dual photoacoustic (PA)/magnetic resonance (MR) imaging capacity can provide guidance for the photothermal therapy (PTT). (3) FeTNPs can be dynamically disassembled by deferoxamine mesylate (DFO) to accelerate elimination of the nanoparticles, thus reducing the potential toxicity for the body. The DFO triggered dynamic disassembling strategy may open a new avenue to overcome the dilemma between EPR effect and renal clearance.


Assuntos
Neoplasias da Mama/terapia , Nanopartículas Multifuncionais/uso terapêutico , Animais , Neoplasias da Mama/diagnóstico por imagem , Feminino , Humanos , Hipertermia Induzida , Células MCF-7 , Imageamento por Ressonância Magnética , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas Multifuncionais/química , Técnicas Fotoacústicas , Ratos Sprague-Dawley , Nanomedicina Teranóstica
19.
J Control Release ; 295: 153-163, 2019 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-30586598

RESUMO

Despite advances in cancer therapy, effective local treatment remains a formidable challenge due to the limit of efficient drug delivery method and the toxicity of chemotherapeutics. In the current study, a combined system was developed for simultaneous delivering doxorubicin (DOX) and cis-platinum (CDDP) to the lungs via pulmonary administration. Methoxy poly(ethylene glycol)-poly(ethylenimine)-poly(l-glutamate) (mPEG-OEI-PLG) copolymers were synthesized as a carrier for the co-delivery of DOX and CDDP. The co-delivery nanoparticles (Co-NPs) were formed with mPEG-OEI-PLG via electrostatic interactions for DOX loading and chelate interactions for CDDP loading, respectively. The results of in vitro cytotoxicity assays against B16F10 cell line showed that Co-NPs exhibited higher cytotoxicity than those treated with either DOX or CDDP alone. In the B16F10 tumor-bearing mice models, local delivery of Co-NPs by pulmonary administration demonstrated that Co-NPs had highly efficient accumulation in the lungs, especially in the tumor tissues of the lungs, but rarely in normal lung tissues. Moreover, Co-NPs exhibited higher anti-tumor efficiency for metastatic lung cancer than that in the single treatment of DOX or CDDP, while no obvious side effects were observed during the pulmonary treatment. The present pulmonary delivery by exploiting co-loaded nanoparticles was proved to be a promising drug delivery strategy for effective lung cancer therapy.


Assuntos
Antineoplásicos/administração & dosagem , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Portadores de Fármacos/química , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Cisplatino/farmacocinética , Cisplatino/uso terapêutico , Doxorrubicina/farmacocinética , Doxorrubicina/uso terapêutico , Neoplasias Pulmonares/patologia , Masculino , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas/química , Polietilenoglicóis/química , Ácido Poliglutâmico/análogos & derivados
20.
ACS Biomater Sci Eng ; 5(9): 4700-4707, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-33448842

RESUMO

Photothermal therapy (PTT) has received extensive attention because of its excellent antitumor effect, specific selectivity, and minimal invasiveness. FeIII-phenol complexes with good biocompatibility and biosafety have widespread applications in PTT. However, the comparison of different FeIII-phenol complexes for photoacoustic imaging (PAI) and PTT has been rarely reported. Herein, we prepared a series of FeIII-phenol complexes using phenols with different structures via a simple one-step method. We then systematically investigated their ultraviolet-visible (UV-vis) absorbance, photothermal performance, and PAI capability. Phenols, including ortho diphenol or triphenol, were important components of FeIII-phenol complexes with strong capacity for UV-vis absorbance, photothermal performance, and PAI. The representative FeIII-pyrocatechol (PC) and FeIII-tannic acid (TA) complexes exhibited excellent photothermal performance and could induce MCF-7 cell death with laser irradiation. Moreover, FeIII-PC and FeIII-TA complexes emitted strong photoacoustic (PA) signals and might be used as PA agents. After comprehensive consideration, FeIII-TA complexes were identified as optimal PTT agents with PAI for cancer treatment. This study has a high reference value for the application of FeIII-phenol complexes to cancer diagnosis and therapy.

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