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1.
Small ; : e2402308, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39114869

RESUMO

Metalloimmunotherapy has achieved great preclinical success against malignant tumors. Nonetheless, the limited immune cell infiltration and impaired immunogenicity within the tumor microenvironment (TME) significantly hinder its translation to clinical applications. In this study, a zinc coordination lipid nanoparticle is developed loaded with calcium peroxide hydrate (CaO2) nanoparticles and the STING agonist diABZI-2, which is termed A-CaO2-Zn-LNP. The release of Zn2+ from the A-CaO2-Zn-LNP and the calcium overload synergistically induced immunogenic cell death (ICD). In addition, CaO2 nanoparticles can consume H+ and release oxygen (O2) under acidic conditions. This treatment increased the pH and alleviated the hypoxia of the TME. Along with cGAS-STING activation by diABZI-2, A-CaO2-Zn-LNP ultimately results in enhanced anti-tumor systemic immunity and long-term immune memory via alleviating the immunosuppressive microenvironment. Taken together, A-CaO2-Zn-LNP offers a new nanoplatform that expands its application for cancer treatment by metalloimmunotheray.

2.
Small ; 19(17): e2206981, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36693779

RESUMO

CRISPR/Cas9-based gene therapy and photodynamic therapy both show promise for cancer treatment but still have their drawbacks limited by tumor microenvironment and long treatment duration. Herein, CRISPR/Cas9 genome editing and photodynamic strategy for a synergistic anti-tumor therapeutic modality is merged. Chlorophyll (Chl) extracted from natural green vegetables is encapsulated in Pluronic F127 (F127) micelles and Histidine-tagged Cas9 can be effectively chelated onto micelles via metal coordination by simple incubation, affording Cas9-Chl@F127 micelles. Mg2+ acts as an enzyme cofactor to correlatively enhance Cas9 gene-editing activity. Upon laser irradiation, Chl as an effective photosensitizer generates reactive oxygen species (ROS) to kill tumor cells. Meanwhile, CRISPR/Cas9, mediated by dual deliberately designed gRNAs of APE1 and NRF2, can reprogram the tumor microenvironment by increasing the intracellular oxygen accumulation and impairing the oxidative defense system of tumor cells. Cas9-Chl@F127 micelles can responsively release Cas9 in the presence of abundant ATP or low pH in tumor cells. In a murine tumor model, Cas9-Chl@F127 complexed with dual gRNAs including APE1 and NRF2 significantly inhibits the tumor growth. Taken together, Cas9-Chl@F127 micelles, representing the first Chl-based green biomaterial for the delivery of Cas9, show great promise for the synergistic anti-tumor treatment by PDT and gene editing.


Assuntos
Neoplasias , Fotoquimioterapia , Camundongos , Animais , Micelas , Edição de Genes , Clorofila , Sistemas CRISPR-Cas/genética , Fator 2 Relacionado a NF-E2 , Neoplasias/genética , Neoplasias/terapia
3.
Small ; 18(6): e2104132, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34850550

RESUMO

Photoacoustic imaging (PA) in the second near infrared (NIR-II) window presents key advantages for deep tissue imaging owing to reduced light scattering and low background signal from biological structures. Here, a thiadiazoloquinoxaline-based semiconducting polymer (SP) with strong absorption in the NIR-II region is reported. After encapsulation of SP in Pluronic F127 (F127) followed by removal of excess surfactant, a dual functional polymer system named surfactant-stripped semiconductor polymeric micelles (SSS-micelles) are generated with water solubility, storage stability, and high photothermal conversion efficiency, permitting tumor theranostics in a mouse model. SSS-micelles have a wideband absorption in the NIR-II window, allowing for the PA imaging at both 1064 and 1300 nm wavelengths. The PA signal of the SSS-micelles can be detected through 6.5 cm of chicken breast tissue in vitro. In mice or rats, SSS-micelles can be visualized in bladder and intestine overlaid 5 cm (signal to noise ratio, SNR ≈ 17 dB) and 5.8 cm (SNR over 10 dB) chicken breast tissue, respectively. This work demonstrates the SSS-micelles as a nanoplatform for deep tissue theranostics.


Assuntos
Nanopartículas , Neoplasias , Técnicas Fotoacústicas , Animais , Camundongos , Micelas , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Técnicas Fotoacústicas/métodos , Fototerapia , Polímeros/química , Medicina de Precisão , Ratos , Tensoativos/química
4.
Bioconjug Chem ; 33(10): 1944-1952, 2022 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-36191256

RESUMO

In the tumor microenvironment, there exist microorganisms that metabolize anticancer drugs, leading to chemotherapy failure. To solve this problem, herein, we develop antibiotic and anticancer drug co-delivery micelles, termed colistin crosslinked gemcitabine micelle (CCGM). A self-immolative linker enables colistin and gemcitabine to be released on demand without affecting their antibacterial and anticancer effects. Once CCGM is delivered to the tumor microenvironment, intracellular glutathione triggers the release of colistin and gemcitabine, inhibiting the growth of microbes in the tumor, thus eliminating the microbe-induced drug resistance of tumor.


Assuntos
Antineoplásicos , Micelas , Colistina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Glutationa , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Linhagem Celular Tumoral , Gencitabina
5.
Int J Mol Sci ; 21(17)2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32887466

RESUMO

Stimulus-responsive drug delivery systems generally aim to release the active pharmaceutical ingredient (API) in response to specific conditions and have recently been explored for disease treatments. These approaches can also be extended to molecular imaging to report on disease diagnosis and management. The stimuli used for activation are based on differences between the environment of the diseased or targeted sites, and normal tissues. Endogenous stimuli include pH, redox reactions, enzymatic activity, temperature and others. Exogenous site-specific stimuli include the use of magnetic fields, light, ultrasound and others. These endogenous or exogenous stimuli lead to structural changes or cleavage of the cargo carrier, leading to release of the API. A wide variety of stimulus-responsive systems have been developed-responsive to both a single stimulus or multiple stimuli-and represent a theranostic tool for disease treatment. In this review, stimuli commonly used in the development of theranostic nanoplatforms are enumerated. An emphasis on chemical structure and property relationships is provided, aiming to focus on insights for the design of stimulus-responsive delivery systems. Several examples of theranostic applications of these stimulus-responsive nanomedicines are discussed.


Assuntos
Sistemas de Liberação de Medicamentos , Nanomedicina , Nanopartículas/administração & dosagem , Nanopartículas/química , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Polímeros/química , Humanos
6.
Adv Healthc Mater ; 13(9): e2303305, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38277491

RESUMO

Nanomedicine in combination with immunotherapy has shown great potential in the cancer treatment, but phototherapeutic nanomaterials that specifically activate the immunopharmacological effects in deep tumors have rarely been developed due to limited laser penetration depth and tumor immune microenvironment. Herein, this work reports a newly synthesized semiconducting polymer (SP) grafted with imiquimod R837 and indoxmid encapsulated micelle (SPRIN-micelle) with strong absorption in the second near infrared window (NIR-II) that can relieve tumor immunosuppression and enhance the photothermal immunotherapy and catabolic modulation on tumors. Immune agonists (Imiquimod R837) and immunometabolic modulators (indoxmid) are covalently attached to NIR-II SP sensors via a glutathione (GSH) responsive self-immolation linker and then loaded into Pluronic F127 (F127) micelles by a temperature-sensitive critical micelle concentration (CMC)-switching method. Using this method, photothermal effect of SPRIN-micelles in deep-seated tumors can be activated, leading to effective tumor ablation and immunogenic cell death (ICD). Meanwhile, imiquimod and indoxmid are tracelessly released in response to the tumor microenvironment, resulting in dendritic cell (DC) maturation by imiquimod R837 and inhibition of both indoleamine 2,3-dioxygenase (IDO) activity and Treg cell expression by indoxmid. Ultimately, cytotoxic T-lymphocyte infiltration and tumor metastasis inhibition in deep solid tumors (9 mm) are achieved. In summary, this work demonstrates a new strategy for the combination of photothermal immunotherapy and metabolic modulation by developing a dual functional polymer system including activable SP and temperature-sensitive F127 for the treatment of deep solid tumors.


Assuntos
Nanopartículas , Neoplasias , Polietilenos , Polipropilenos , Humanos , Imiquimode/farmacologia , Polímeros/farmacologia , Micelas , Fototerapia/métodos , Neoplasias/tratamento farmacológico , Imunoterapia/métodos , Linhagem Celular Tumoral , Microambiente Tumoral
7.
ACS Appl Bio Mater ; 7(5): 3306-3315, 2024 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-38634490

RESUMO

Photodynamic therapy (PDT) and ferroptosis show significant potential in tumor treatment. However, their therapeutic efficacy is often hindered by the oxygen-deficient tumor microenvironment and the challenges associated with efficient intracellular drug delivery into tumor cells. Toward this end, this work synthesized perfluorocarbon (PFC)-modified Pluronic F127 (PFC-F127), and then exploits it as a carrier for codelivery of photosensitizer Chlorin e6 (Ce6) and the ferroptosis promoter sorafenib (Sor), yielding an oxygen self-supplying nanoplatform denoted as Ce6-Sor@PFC-F127. The PFCs on the surface of the micelle play a crucial role in efficiently solubilizing and delivering oxygen as well as increasing the hydrophobicity of the micelle surface, giving rise to enhanced endocytosis by cancer cells. The incorporation of an oxygen-carrying moiety into the micelles enhances the therapeutic impact of PDT and ferroptosis, leading to amplified endocytosis and cytotoxicity of tumor cells. Hypotonic saline technology was developed to enhance the cargo encapsulation efficiency. Notably, in a murine tumor model, Ce6-Sor@PFC-F127 effectively inhibited tumor growth through the combined use of oxygen-enhanced PDT and ferroptosis. Taken together, this work underscores the promising potential of Ce6-Sor@PFC-F127 as a multifunctional therapeutic nanoplatform for the codelivery of multiple cargos such as oxygen, photosensitizers, and ferroptosis inducers.


Assuntos
Antineoplásicos , Clorofilídeos , Ensaios de Seleção de Medicamentos Antitumorais , Ferroptose , Fluorocarbonos , Micelas , Oxigênio , Fotoquimioterapia , Fármacos Fotossensibilizantes , Ferroptose/efeitos dos fármacos , Fluorocarbonos/química , Fluorocarbonos/farmacologia , Animais , Camundongos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/síntese química , Humanos , Oxigênio/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Teste de Materiais , Tamanho da Partícula , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/síntese química , Porfirinas/química , Porfirinas/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Sorafenibe/química , Sorafenibe/farmacologia , Sorafenibe/administração & dosagem , Poloxâmero/química , Linhagem Celular Tumoral , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Neoplasias Experimentais/metabolismo , Estrutura Molecular
8.
ACS Nano ; 18(33): 21855-21872, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39109520

RESUMO

Malignant pleural effusions (MPEs) are hard to treat, and their onset usually signals terminal cancer. Immunotherapies hold promise but must overcome the immunosuppressive MPE microenvironment. Herein, we treat MPEs via synergistically combining two emerging cancer therapy modalities: enzyme-dynamic therapy (EDT) and metalloimmunotherapy. To do so, a nanoplatform termed "A-R-SOME" was developed which comprises MPE-targeted M1 type extracellular vesicles (EVs) loaded with (1) a manganese-based superoxide dismutase (SOD) enzyme, (2) stimulator of interferon genes (STING) agonist diABZI-2, and (3) signal transducer and an activator of transcription 3 (STAT3) small interfering RNA. Endogenous reactive oxygen species within tumors induced immunogenic cell death by EDT, along with STING activation by both Mn and diABZI-2, and suppression of the STAT3 pathway. Systemically administered A-R-SOME alleviated the MPE immunosuppressive microenvironment, triggered antitumor systemic immunity, and long-term immune memory, leading to the complete eradication of MPE and pleural tumors with 100% survival rate in an aggressive murine model. A-R-SOME-induced immune effects were also observed in human patient-derived MPE, pointing toward the translation potential of A-R-SOME as an experimental malignancy treatment.


Assuntos
Vesículas Extracelulares , Imunoterapia , Derrame Pleural Maligno , Vesículas Extracelulares/química , Vesículas Extracelulares/metabolismo , Animais , Humanos , Camundongos , Superóxido Dismutase/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , RNA Interferente Pequeno/genética , Feminino , Fator de Transcrição STAT3/metabolismo , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral
9.
J Control Release ; 357: 210-221, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36972864

RESUMO

CRISPR-Cas9 is a central focus of the emerging field of gene editing and photodynamic therapy (PDT) is a clinical-stage ablation modality combining photosensitizers with light irradiation. But metal coordination biomaterials for the applications of both have rarely been investigated. Herein, Chlorin-e6 (Ce6) Manganese (Mn) coordination micelles loaded with Cas9, termed Ce6-Mn-Cas9, were developed for augmented combination anti-cancer treatment. Manganese played multiple roles to facilitate Cas9 and single guide RNA (sgRNA) ribonucleoprotein (RNP) delivery, Fenton-like effect, and enhanced endonuclease activity of RNP. Histidine (His)-tagged RNP could be coordinated to Ce6 encapsulated in Pluronic F127 (F127) micelles by simple admixture. Triggered by ATP and endolysosomal acidic pH, Ce6-Mn-Cas9 released Cas9 without altering protein structure or function. Dual guide RNAs were designed to target the antioxidant regulator MTH1 and the DNA repair protein APE1, resulting in increased oxygen and enhanced PDT effect. In a murine tumor model, Ce6-Mn-Cas9 inhibited tumor growth with the combination therapy of PDT and gene editing. Taken together, Ce6-Mn-Cas9 represents a new biomaterial with a high degree of versatility to enable photo- and gene-therapy approaches.


Assuntos
Neoplasias , Fotoquimioterapia , Porfirinas , Humanos , Animais , Camundongos , Fotoquimioterapia/métodos , Micelas , Manganês , Edição de Genes , Fototerapia , Fármacos Fotossensibilizantes/química , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Porfirinas/química , Linhagem Celular Tumoral
10.
J Biomed Mater Res A ; 110(9): 1590-1598, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35593460

RESUMO

Colistin is a potent antibiotic but its severe side effects including nephrotoxicity and neurotoxicity are the roadblock for their wide use in clinics. To solve this problem, we synthesized a new prodrug, mannose-maltose-colistin conjugate, termed MMCC that can reversibly mask the five amines of colistin that are primarily responsible for the toxicity. The deliberated design of disulfide-based self-immolative linker warranted the reversibly release of the pristine amines of colistin on demand without sacrificing antimicrobial efficacy. Once MMCC was delivered in cells, reducing agents cleaves the disulfide bond and release the pristine amines. The targeting ligands of maltose and mannose were grafted on colistin conjugate for targeting delivery of colistin to bacteria and macrophages, respectively. Taken together, MMCC as a new class of antimicrobial biomaterials, demonstrates its great potential for the treatment of intracellular bacterial infections.


Assuntos
Infecções Bacterianas , Pró-Fármacos , Aminas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Colistina/química , Colistina/uso terapêutico , Dissulfetos , Humanos , Maltose , Manose , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico
11.
J Control Release ; 341: 329-340, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34843813

RESUMO

Effective delivery of antimicrobial agents to intracellular pathogens represents a major bottleneck for a wide variety of infectious diseases. To address this, we developed SIR-micelles(+), as a new delivery vehicle comprising antibiotic-loaded micelles with rapid self-immolation within cells for targeted delivery to macrophages, where most intracellular bacterial reside. After phagocytosis, SIR-micelles(+) rapidly release the pristine antibiotic after the cleavage of the disulfide bonds by intracellular reducing agents such as glutathione (GSH). Colistin, a hydrophilic and potent "last-resort" antibiotic used for the treatment of drug-resistant bacterial infection, was encapsulated in SIR-micelles with 40% yield and good short-term storage stability. Hydrophobic moieties and mannose ligands in SIR-micelles(+) enhanced the delivery of colistin into macrophages. The traceless and thiol-responsive release of colistin effectively eliminated intracellular Escherichia coli within twenty minutes. In a murine pneumonia model, SIR-micelles(+) significantly reduced bacterial lung burden of multidrug-resistant Klebsiella pneumoniae. Furthermore, SIR-micelles(+) improved the survival rate and reduced the bacterial burden of organs infected by intracellular bacteria transferred from donor mice. Using this formulation approach, the nephrotoxicity and neurotoxicity induced by antibiotic were reduced by about 5- 15 fold. Thus, SIR-micelles(+) represent a new class of material that can be used for targeting treatment of intracellular and drug-resistant pathogens.


Assuntos
Antibacterianos , Micelas , Animais , Colistina , Escherichia coli , Glutationa/química , Camundongos
12.
Adv Healthc Mater ; 11(10): e2102365, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34989166

RESUMO

CRISPR-Cas9 as a powerful gene-editing tool has tremendous potential for the treatment of genetic diseases. Herein, a new mesoporous nanoflower (NF)-like delivery nanoplatform termed Cas9-NF is reported by crosslinking Cas9 and polymeric micelles that enables efficient intracellular delivery and controlled release of Cas9 in response to reductive microenvironment in tumor cells. The flower morphology is flexibly tunable by the protein concentration and different types of crosslinkers. Cas9 protein, embedded between polymeric micelles and protected by Cas9-NF, remains stable even under extreme pH conditions. Responsive cleavage of crosslinkers in tumor cells, leads to the traceless release of Cas9 for efficient gene knockout in nucleus. This crosslinked nanoparticle exhibits excellent capability of downregulating oncogene expression and inhibiting tumor growth in a murine tumor model. Taken together, these findings pave a new pathway toward the application of the protein-micelle crosslinked nanoflower for protein delivery, which warrants further investigations for gene regulation and cancer treatment.


Assuntos
Edição de Genes , Nanopartículas , Animais , Proteína 9 Associada à CRISPR/genética , Sistemas CRISPR-Cas/genética , Camundongos , Micelas , Polímeros/metabolismo
13.
ACS Appl Mater Interfaces ; 14(2): 2510-2521, 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-34986639

RESUMO

The development of nanocarriers capable of codelivering antigens and immune-activating adjuvants is an emerging area of research and is relevant for cancer vaccines that target induction of antigen-specific CD8+ T-cell responses. Here, we report a system for delivery of short peptide antigens to dendritic cells for strong cellular immune responses, based on block copolymers chemically modified with a hydrophobic and self-immolative linker. After modification, micelles effectively and reversibly capture antigens and adjuvants via a covalent bond within several minutes in an aqueous solution. After uptake in antigen presenting cells, the polymer disulfide bond is cleaved by intracellular glutathione, leading to release of pristine antigens, along with the upregulated expression of costimulatory molecules. The induced antigen-specific CD8+ T cells have strong tumor cell killing efficacy in the murine B16OVA and human papilloma virus-E6/E7 subcutaneous and lung metastasis tumor models. In addition, delivery to lymph nodes can be imaged to visualize vaccine trafficking. Taken together, multifunctional self-immolative micelles represent a versatile class of a vaccine delivery system for the generation of a cellular immune response that warrants further exploration as a component of cancer immunotherapy.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Vacinas Anticâncer/imunologia , Epitopos de Linfócito T/imunologia , Imunoterapia , Neoplasias Pulmonares/terapia , Adjuvantes Imunológicos , Animais , Humanos , Neoplasias Pulmonares/imunologia , Teste de Materiais , Camundongos , Micelas , Vacinação
14.
ACS Appl Bio Mater ; 4(6): 4982-4989, 2021 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-35007046

RESUMO

Prodrugs can be formed by chemical modification of the existing active pharmaceutical ingredients (APIs); however, this often sacrifices their functional efficacy. Self-immolative linkers have recently attracted attention, as they can be designed to release pristine APIs. Herein, we report a strategy to generate a self-immolative prodrug (SIP) that can release pristine doxorubicin (DOX). Compared to conventional linkers, the key SIP DOX (KSIP-DOX) developed here can rapidly and quantitatively release the API due to its strong leaving group after reduction by thiol groups, which are present in tumors. KSIP-DOX has enhanced cellular uptake and improved anticancer efficacy, demonstrating its utility for cancer treatment.


Assuntos
Antibióticos Antineoplásicos , Doxorrubicina , Pró-Fármacos , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/toxicidade , Linhagem Celular Tumoral , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/toxicidade , Desenho de Fármacos , Liberação Controlada de Fármacos , Feminino , Glutationa/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias/tratamento farmacológico , Pró-Fármacos/administração & dosagem , Pró-Fármacos/química , Pró-Fármacos/farmacocinética , Pró-Fármacos/toxicidade
15.
ACS Appl Mater Interfaces ; 13(8): 9630-9642, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33616382

RESUMO

One potential approach to address the rising threat of antibiotic resistance is through novel formulations of established drugs. We designed antibiotic cross-linked micelles (ABC-micelles) by cross-linking the Pluronic F127 block copolymers with an antibiotic itself, via a novel one-pot synthesis in aqueous solution. ABC-micelles enhanced antibiotic encapsulation while also reducing systemic toxicity in mice. Using colistin, a hydrophilic, potent ″last-resort" antibiotic, ABC-micelle encapsulation yield was 80%, with good storage stability. ABC-micelles exhibited an improved safety profile, with a maximum tolerated dose of over 100 mg/kg colistin in mice, at least 16 times higher than the free drug. Colistin-induced nephrotoxicity and neurotoxicity were reduced in ABC-micelles by 10-50-fold. Despite reduced toxicity, ABC-micelles preserved bactericidal activity, and the clinically relevant combination of colistin and rifampicin (co-loaded in the micelles) showed a synergistic antimicrobial effect against antibiotic-resistant strains of Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii. In a mouse model of sepsis, colistin ABC-micelles showed equivalent efficacy as free colistin but with a substantially higher therapeutic index. Microscopic single-cell imaging of bacteria revealed that ABC-micelles could kill bacteria in a more rapid manner with distinct cell membrane disruption, possibly reflecting a different antimicrobial mechanism from free colistin. This work shows the potential of drug cross-linked micelles as a new class of biomaterials formed from existing antibiotics and represents a new and generalized approach for formulating amine-containing drugs.


Assuntos
Antibacterianos/uso terapêutico , Colistina/uso terapêutico , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Micelas , Sepse/tratamento farmacológico , Animais , Antibacterianos/síntese química , Antibacterianos/toxicidade , Bactérias/efeitos dos fármacos , Colistina/síntese química , Colistina/toxicidade , Ciclofosfamida , Feminino , Camundongos , Testes de Sensibilidade Microbiana , Síndromes Neurotóxicas/prevenção & controle , Poloxâmero/síntese química , Poloxâmero/química , Poloxâmero/toxicidade , Sepse/induzido quimicamente
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