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1.
Macromol Rapid Commun ; : e2400136, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38593288

RESUMO

In this work, a natural medicine, baicalin, is designed for the treatment of psoriasis with the aid of hyaluronic acid (HA)-based MNs patches. This is also to improve the solubility of baicalin and increase its residence time in infected part, which is made into nanoparticles by complexation with humic acid and Eu2+. The baicalin nanoparticles loaded-MNs exhibit satisfactory rigidity, minimum injury, and controlled drug delivery. The anti-reactive oxygen species (anti-ROS) and anti-inflammatory action are verified by the effective scavenging oxygen and nitrogen radicals. In addition, the loading of baicalin nanoparticles brings remarkable photothermic effect to the MNs, enabling the device to release a controlled drug under near-infrared region II (NIR-II) laser irradiation. With the aid of NIR-II laser, the baicalin-mediated treatment of psoriasis is significantly improved by expediting radical scavenging and suppressing inflammation. The design of baicalin MNs provides a new idea for the treatment of chronic disease.

2.
Small ; 19(21): e2300244, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36843276

RESUMO

Energy band structure of inorganic nano-sonosensitizers is usually optimized by surface decoration with noble metals or metal oxide semiconductors, aiming to enhance interfacial charge transfer, augment spin-flip and promote radical generation. To avoid potential biohazards of metallic elements, herein, metal-free graphitic carbon nitride quantum dots (g-C3 N4 QDs) are anchored onto hollow mesoporous TiO2 nanostructure to formulate TiO2 @g-C3 N4 heterojunction. The direct Z-scheme charge transfer significantly improves the separation/recombination dynamics of electron/hole (e- /h+ ) pairs upon ultrasound (US) stimulation, which promotes the yield of singlet oxygen (1 O2 ) and hydroxyl radicals (·OH). The conjugated g-C3 N4 QDs with peroxidase-mimic activity further react with the elevated endogenous H2 O2 and aggravate oxidative stress. After loading prodrug romidepsin (RMD) in TiO2 @g-C3 N4 , stimulus-responsive drug delivery can be realized by US irradiation. The disulfide bridge of the released RMD tends to be reduced by glutathione (GSH) into a monocyclic dithiol, which arrests cell cycle in G2/M phase and evokes apoptosis through enhanced histone acetylation. Importantly, reactive oxygen species accumulation accompanied by GSH depletion is devoted to deleterious redox dyshomeostasis, leading to augmented systemic oncotherapy by eliciting antitumor immunity. Collectively, this paradigm provides useful insights in optimizing the performance of TiO2 -based nano-sonosensitizers for tackling critical diseases.


Assuntos
Óxidos , Oxirredução , Ultrassonografia , Acetilação
3.
Small ; 19(24): e2206912, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36932931

RESUMO

Enzyme-instructed self-assembly of bioactive molecules into nanobundles inside cells is conceived to potentially disrupt plasma membrane and subcellular structure. Herein, an alkaline phosphatase (ALP)-activatable hybrid of ICG-CF4 KYp is facilely synthesized by conjugating photosensitizer indocyanine green (ICG) with CF4 KYp peptide via classical Michael addition reaction. ALP-induced dephosphorylation of ICG-CF4 KYp enables its transformation from small-molecule precursor into rigid nanofibrils, and such fibrillation in situ causes severe mechanical disruption of cytomembrane. Besides, ICG-mediated photosensitization causes additional oxidative damage of plasma membrane by lipid peroxidation. Hollow MnO2 nanospheres devote to deliver ICG-CF4 KYp into tumorous tissue through tumor-specific acidity/glutathione-triggered degradation of MnO2 , which is monitored by fluorescent probing and magnetic resonance imaging. The burst release of damage-associated molecular patterns and other tumor antigens during therapy effectively triggers immunogenetic cell death and improves immune stimulatory, as demonstrated by the promotion of dendritic cell maturation and CD8+ lymphocyte infiltration, as well as constraint of regulatory T cell population. Taken together, such cytomembrane injury strategy based on peptide fibrillation in situ holds high clinical promise for lesion-specific elimination of primary, abscopal, and metastatic tumors, which may enlighten more bioinspired nanoplatforms for anticancer theranostics.


Assuntos
Compostos de Manganês , Fotoquimioterapia , Óxidos , Fármacos Fotossensibilizantes/química , Verde de Indocianina/química , Corantes/química , Peptídeos , Fosfatase Alcalina , Membrana Celular/metabolismo , Fotoquimioterapia/métodos , Linhagem Celular Tumoral
4.
Small ; : e2307404, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38054772

RESUMO

Mitochondria are core regulators of tumor cell homeostasis, and their damage has become an arresting therapeutic modality against cancer. Despite the development of many mitochondrial-targeted pharmaceutical agents, the exploration of more powerful and multifunctional medications is still underway. Herein, oxygen vacancy-rich BiO2-x wrapped with CaCO3 (named BiO2-x @CaCO3 /PEG, BCP) is developed for full-fledged attack on mitochondrial function. After endocytosis of BCP by tumor cells, the CaCO3 shell can be decomposed in the acidic lysosomal compartment, leading to immediate Ca2+ release and CO2 production in the cytoplasm. Near-infrared irradiation enhances the adsorption of CO2 onto BiO2-x defects, which enables highly efficient photocatalysis of CO2 -to-CO. Meanwhile, such BiO2-x nanosheets possess catalase-, peroxidase- and oxidase-like catalytic activities under acidic pH conditions, allowing hypoxia relief and the accumulation of diverse reactive oxygen species (ROS) in the tumor microenvironment. Ca2+ overload-induced ion dyshomeostasis, CO-mediated respiratory chain poisoning, ROS-triggered oxidative stress aggravation, and cytosolic hyperoxia can cause severe mitochondrial disorders, which further lead to type I cell death in carcinoma. Not only does BCP cause irreversible apoptosis, but immunogenic cell death is simultaneously triggered to activate antitumor immunity for metastasis inhibition. Collectively, this platform promises high benefits in malignant tumor therapy and may expand the medical applications of bismuth-based nanoagents.

5.
Mikrochim Acta ; 190(6): 228, 2023 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-37204518

RESUMO

Despite black phosphorous (BP) QDs possess the merits of size-tunable band-gap, high electron mobility, and intrinsic defects, the spontaneous agglomeration and rapid oxidation of BP QDs in aqueous solution caused low electrochemiluminescence (ECL) efficiency and unstable ECL signal, which confined its further application of biological analysis. Herein, polyethylene glycol-functionalized BP QDs (PEG@BP QDs) were prepared showing an efficient and stable ECL response, which is attributed to the fact that PEG as protectant not only effectively prevented the spontaneous agglomeration, but also restrained the rapid oxidation of BP QDs in aqueous solution. As proof-of-concept, PEG@BP QDs were used as an efficient ECL emitter to combine with palindrome amplification-induced DNA walker to construct a sensitive ECL aptasensing platform for detecting cancer marker mucin 1 (MUC1). Interestingly, with the aid of positively charged thiolated PEG, the reaction rate of DNA walker on the electrode interface was clearly increased for the recovery of the ECL signal. The ECL aptasensor provides sensitive determination with the detection limit of 16.5 fg/mL. The proposed strategy paves a path for the development of efficient and stable ECL nanomaterials to construct biosensors for biosensing and clinical diagnosis.


Assuntos
Pontos Quânticos , Medições Luminescentes , Biomarcadores Tumorais , Fotometria , Água , DNA
6.
Chem Soc Rev ; 51(12): 5136-5174, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35666131

RESUMO

Recent years have witnessed increasingly rapid advances in nanocarrier-based biomedicine aimed at improving treatment paradigms for cancer. Nanogels serve as multipurpose and constructed vectors formed via intramolecular cross-linking to generate drug delivery systems, which is attributed predominantly to their satisfactory biocompatibility, bio-responsiveness, high stability, and low toxicity. Recently, immunotherapy has experienced unprecedented growth and has become the preferred strategy for cancer treatment, and mainly involves the mobilisation of the immune system and an enhanced anti-tumour immunity of the tumour microenvironment. Despite the inspiring success, immunotherapeutic strategies are limited due to the low response rates and immune-related adverse events. Like other nanomedicines, nanogels are comparably limited by lower focal enrichment rates upon introduction into the organism via injection. Because nanogels are three-dimensional cross-linked aqueous materials that exhibit similar properties to natural tissues and are structurally stable, they can comfortably cope with shear forces and serum proteins in the bloodstream, and the longer circulation life increases the chance of nanogel accumulation in the tumour, conferring deep tumour penetration. The large specific surface area can reduce or eliminate off-target effects by introducing stimuli-responsive functional groups, allowing multiple physical and chemical modifications for specific purposes to improve targeting to specific immune cell subpopulations or immune organs, increasing the bioavailability of the drug, and conferring a low immune-related adverse events on nanogel therapies. The slow release upon reaching the tumour site facilitates long-term awakening of the host's immune system, ultimately achieving enhanced therapeutic effects. As an effective candidate for cancer immunotherapy, nanogel-based immunotherapy has been widely used. In this review, we mainly summarize the recent advances of nanogel-based immunotherapy to deliver immunomodulatory small molecule drugs, antibodies, genes and cytokines, to target antigen presenting cells, form cancer vaccines, and enable chimeric antigen receptor (CAR)-T cell therapy. Future challenges as well as expected and feasible prospects for clinical treatment are also highlighted.


Assuntos
Vacinas Anticâncer , Neoplasias , Sistemas de Liberação de Medicamentos , Humanos , Imunoterapia/métodos , Nanogéis , Neoplasias/tratamento farmacológico , Microambiente Tumoral
7.
Small ; 18(2): e2104302, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34761867

RESUMO

Here, acidic tumor microenvironment (TME)-responsive nano-Bi2 Se3 @MnCaP, as a near-infrared-II (NIR-II) biowindow-triggered free radical generator for hypoxia-irrelevant phototherapy, is elaborately developed by biomimetic mineralization of MnCaP onto 2, 2'-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIPH)-loaded mesoporous nano-Bi2 Se3 to form Bi2 Se3 /AIPH@MnCaP (BAM). Surface mineral of MnCaP can be degraded under mild acidity, leading to the release of both Mn2+ and AIPH. The leached Mn2+ not only facilitates chemodynamic therapy (CDT) via hydroxyl radicals (• OH) from Mn2+ -mediated Fenton-like reaction but also acts as contrast agent for magnetic resonance imaging. In another aspect, the splendid photothermal conversion capacity of BAM enables a rapid hyperthermia generation under NIR-II laser irradiation for photothermal therapy (PTT). Simultaneously, the local thermal shock can induce the disintegration of AIPH to generate alkyl radicals (• R) for thermodynamic therapy (TDT) and accelerate Fenton-like reaction rate to augment CDT efficacy. The strong synergistic effects from cooperative CDT/PTT/TDT are applied to 4T1 tumor suppression with minimal side effects. Importantly, the combination therapy can effectively trigger immunogenetic cell death and enhance antitumor immunity for systemic tumor eradication. Collectively, this proof-of-concept study demonstrates a more efficacious and safer strategy for oxygenation-independent phototherapy, which holds a good potential for clinical translation in cancer management.


Assuntos
Nanopartículas , Neoplasias , Linhagem Celular Tumoral , Radicais Livres , Humanos , Hipóxia/tratamento farmacológico , Neoplasias/tratamento farmacológico , Fototerapia , Microambiente Tumoral
8.
Small ; 18(38): e2203080, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35989099

RESUMO

The therapeutic exploration of nano-zirconia semiconductor largely remains untouched in the field of fundamental science to date. Here, a robust nano-sonosensitizer of ZrO2- x @Pt is strategically formulated by in situ growth of Pt nanocrystal onto the surface of oxygen-deficient ZrO2- x . Compared to 3.09 eV of nano-ZrO2- x , the bandgap of ZrO2- x @Pt Schottky junction is narrowed down to 2.74 eV. The band bending and bandgap narrowing enables an enhanced e- /h+ separation in the presence of aPt electron sink, which facilitates a high yield of singlet oxygen (1 O2 ) and hydroxyl radicals (·OH) under ultrasound (US) irradiation. Moreover, nanozyme Pt with catalase-mimic activity can promote 1 O2  generation by relieving the hypoxic tumor microenvironment. Upon further modification of 2,2'-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIPH), US-stimulated local thermal shock can disintegrate AIPH to create cytotoxic alkyl radicals (• R). US-triggered reactive oxygen species generation and hyperthermia-induced alkyl radical production lead to severe and irreversible tumor cell death. Such combinatorial sonodynamic-thermodynamic therapy benefits the tumor eradication and metastasis inhibition at the animal level, with the aid of immunogenetic cell death and immune checkpoint blockade. Taken together, this proof-of-concept paradigm expands the medical use of nano-zirconia and provides useful insights for its therapeutic perspectives.


Assuntos
Neoplasias , Terapia por Ultrassom , Animais , Catalase/metabolismo , Linhagem Celular Tumoral , Inibidores de Checkpoint Imunológico , Neoplasias/terapia , Estresse Oxidativo , Oxigênio , Platina , Propano , Espécies Reativas de Oxigênio/metabolismo , Oxigênio Singlete , Termodinâmica , Microambiente Tumoral
9.
Analyst ; 146(3): 989-996, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33295357

RESUMO

An up-conversion luminescent material converts low-frequency excitation light into high-frequency emission light through photons and has the advantages of long fluorescence lifetime, narrow emission peak and low toxicity; thus, this material has many unique applications in the detection and identification of biomolecules. In this study, an ultrasensitive up-conversion luminescent system for the quantitative detection of morphine was developed. The principle of this system is based on infrared light as an excitation light source to convert light with lower energy into excitation light with higher energy. The up-conversion luminescent material is used as a label and through the processing and analysis of the excitation light intensity, the quantitative detection of morphine concentration is achieved. At the same time, the excitation light can avoid the interference and scattering phenomenon of the autofluorescence of the biological sample, which improves the system's detection sensitivity. An algorithm for light intensity processing is added to process image data, reduce the interference caused by noise during image acquisition and improve the accuracy of morphine detection. The T/C value is calculated to achieve the quantitative detection of morphine with a detection limit of 0.1 ng mg-1 and detection time within 0.5 min. The up-conversion luminescent system has the advantages of quantitative detection, convenience, portability, short detection time and low price. Thus, the system can be used for the detection of other biomolecules or for other applications such as food analysis, environmental detection, national security, etc.


Assuntos
Luminescência , Morfina , Fluorescência , Raios Infravermelhos , Medições Luminescentes , Fótons
10.
Small ; 16(19): e2000214, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32309900

RESUMO

Nanoparticle-based tumor immunotherapy has emerged to show great potential for simultaneously regulating the immunosuppressive tumor microenvironment, reducing the unpleasant side effects, and activating tumor immunity. Herein, an excipient-free glutathione/pH dual-responsive prodrug nanoplatform is reported for immunotherapy, simply by sequentially liberating 5-aminolevulinic acid and immunogenically inducing doxorubicin drug molecules, which can leverage the acidity and reverse tumor microenvironment. The obtained nanoplatform effectively boosts the immune system by promoting dendritic cell maturation and reducing the number of immune suppressive immune cells, which shows the enhanced adjunctive effect of anti-programmed cell death protein 1 therapy. Overall, the prodrug-based immunotherapy nanoplatform may offer a reliable strategy for improving synergistic antitumor efficacy.


Assuntos
Neoplasias , Pró-Fármacos , Humanos , Morte Celular Imunogênica , Imunoterapia , Nanomedicina , Neoplasias/tratamento farmacológico , Microambiente Tumoral
11.
Electrophoresis ; 41(10-11): 811-820, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32097991

RESUMO

Ion concentration polarization (ICP) imposes remarkable adverse effects on the energy conversion performance of the pressure-driven electrokinetic (EK) flows through a capillary system that can be equivalently treated as a battery. An optimized dimensionless numerical method is proposed in this study to investigate the causes and the effects of the ICP. Results show that remarkable ICP phenomena are induced under certain conditions such as high applied pressure, high surface charge density, and small inversed Debye length at dimensionless values of 6000, -10, and 0.5. Meanwhile, different factors influence the ICP and the corresponding electric properties in different ways. Particularly for the overall electric resistance, the applied pressure and the surface charge density mainly affect the variation amplitude and the level of the overall electric resistance when varying the output electric potential, respectively. Differently, the Debye length affects the overall electric resistance in both aspects. Ultimately, the induced ICP leads to significant nonlinear current-potential curves.


Assuntos
Fontes de Energia Elétrica , Técnicas Eletroquímicas/instrumentação , Desenho de Equipamento , Íons/química , Dinâmica não Linear
12.
Electrophoresis ; 40(6): 922-929, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30597589

RESUMO

Spatial microgravity is a significant factor affecting and causing physiological changes of organisms in space environment. On-site assessment of the damage associated to microgravity is very important for future long-term space exploration of mankind. In this paper, a new microfluidic device for analyzing the damage of microgravity on Caenorhabditis elegans (C. elegans) has been developed. This device is mainly composed of a microfluidic chip, a dual imaging module, and an imaging acquisition and processing module, which are integrated into a compact system. The microfluidic chip is designed as a platform for monitoring C. elegans, which is captured in an imaging region through a suction structure in the microfluidic chip. A dual imaging module is designed to obtain the images of bright field and fluorescence of C. elegans. The behaviors of C. elegans are analyzed based on the dual-mode imaging of bright field and fluorescence to assess the degree of damage due to microgravity. A comparative study using a commercial microscope is also conducted to demonstrate the unique advantage of the developed system under the simulated microgravity. The results show that the developed system can evaluate the damage of C. elegans under microgravity accurately and conveniently. Furthermore, this device has compact size and weight, easy operation, and low-cost, which could be highly advantageous for on-site evaluation of the damage to microorganisms under microgravity in a space station.


Assuntos
Caenorhabditis elegans/fisiologia , Processamento de Imagem Assistida por Computador/métodos , Dispositivos Lab-On-A-Chip , Técnicas Analíticas Microfluídicas , Ausência de Peso/efeitos adversos , Animais , Desenho de Equipamento , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodos
13.
Biomed Microdevices ; 21(3): 58, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-31227909

RESUMO

Traditional immunomagnetic assays for the isolation and recovery of circulating tumor cells (CTCs) usually require sophisticated device or intense magnetic field to simultaneously achieve high capture efficiency and high throughout. In this study, a simple microfluidic chip featured with nanoroughened channel substrate was developed for effectively capture and release of CTCs based on an immunomagnetic chip-based approach. The nanoroughened substrate aims to increase the cell-surface contact area, facilitate the immobilization of magnet particles (MPs) and accommodate cell attachment tendency. Hep3B tumor cells were firstly conjugated with MPs that were functionalized with anti-EpCAM. Comparing with the flat channel, MPs modified tumor cells can be more effectively captured on nanoroughened substrate at the presence of the magnetic field. Upon the removal of magnetic field, these captured cells can be released from the device and collected for further analysis. Under the optimum operating conditions, the capture efficiency of tumor cells was obtained as high as ~90% with a detection limit of 10 cell per mL. Additionally, recovery rates of trapped tumor cells at various densities all exceeded 90% and their biological potencies were well retained by investigating the cell attachment and proliferation. Therefore, the present approach may potentially be used in clinical CTC analysis for cancer diagnosis and prognosis as well as the fundamental understanding of tumor metastasis.


Assuntos
Dimetilpolisiloxanos/química , Separação Imunomagnética/instrumentação , Nanoestruturas/química , Células Neoplásicas Circulantes/patologia , Adesão Celular , Linhagem Celular Tumoral , Proliferação de Células , Molécula de Adesão da Célula Epitelial/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Células Neoplásicas Circulantes/metabolismo , Propriedades de Superfície , Fatores de Tempo
14.
Langmuir ; 35(28): 9246-9254, 2019 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-31251628

RESUMO

Design and construction of multifunctional theranostic nanoplatforms are still desired for cancer-effective treatment. Herein, a kind of polypyrrole (PPy)-based multifunctional nanocomposite was designed and successfully constructed for dual-model imaging and enhanced synergistic phototherapy against cancer cells. Through graphene oxide (GO) sheet coating, PPy nanoparticles (NPs) were effectively combined with polyethylene glycol chains, Au NPs, and IR820 molecules. The obtained PGPAI NPs showed promising ability for photoacoustic/computed tomography imaging. Under near-infrared light irradiation, the PPy core and IR820 molecule effectively generated heat and reactive oxygen species (ROS), respectively. Furthermore, the loaded Au NPs owning catalase-like activity produced oxygen by decomposing H2O2 (up-regulated in tumor region), enhancing the oxygen-dependent photodynamic therapy efficacy. The formed PGPAI NPs were also proved to own desirable photothermal conversion efficiency, photothermal stability, colloidal stability, cytocompatibility, and cellular internalization behaviors. Furthermore, cell assay demonstrated that PGPAI NPs displayed enhanced synergistic phototherapy efficacy against cancer cells. These developed multifunctional nanoplatforms are promising for effective cancer theranostic applications.


Assuntos
Nanocompostos/química , Imagem Óptica , Fototerapia , Polímeros/química , Pirróis/química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Células HeLa , Humanos , Camundongos , Tamanho da Partícula , Polímeros/farmacologia , Pirróis/farmacologia , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismo , Propriedades de Superfície
15.
Biomacromolecules ; 20(3): 1334-1345, 2019 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-30703318

RESUMO

Polymeric microneedles have attracted increasing attention as a minimally invasive platform for delivering drugs or vaccines in a more patient-friendly manner. However, traditional microfabrication techniques using negative molds with needle-shaped cavities usually require cumbersome centrifugation and vacuum degassing processes, which have restricted the scaled-up mass production of polymeric microneedles. Herein, a novel polydimethylsiloxane (PDMS)-based negative mold with cavities packed with silk fibroin scaffold is developed for rapid fabrication of polymeric microneedles, which comprise primarily the composition of poly(ethylene glycol) diacrylate (PEGDA) and sucrose as the needle matrix. Fibroin scaffolds can instantly adsorb prepolymer solution due to capillary force, and subsequently initiate the formation of microneedles via photoinduced polymerization. Based on three types of model drugs, including Rhodamine B (RhB), indocyanine green (ICG), and doxorubicin (DOX), the fabricated PEGDA/sucrose microneedles can realize effective transdermal delivery and controllable release of therapeutic molecules by regulating the sucrose content. The presented method provides a simple strategy for quick fabrication of polymeric microneedles toward transdermal drug delivery applications.


Assuntos
Administração Cutânea , Sistemas de Liberação de Medicamentos , Fibroínas/química , Agulhas , Polietilenoglicóis/química , Sacarose/química , Animais , Doxorrubicina/administração & dosagem , Células Endoteliais da Veia Umbilical Humana , Humanos , Verde de Indocianina/administração & dosagem , Camundongos , Porosidade , Rodaminas/administração & dosagem
16.
Biomacromolecules ; 20(3): 1190-1202, 2019 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-30658038

RESUMO

Polymeric prodrug based on therapeutic nanomedicine has demonstrated great promise for effective tumor growth inhibition, however, the drawbacks of low drug-loading and weak micellar stability limit its application for clinical cancer therapy. Herein, a reduction-responsive starburst block copolymer prodrug CCP [ß-cyclodextrin (ß-CD)-PCPTXX-POEGMA, XX: SS or CC] has been developed for cancer therapy. And CCP is composed of ß-CD-Br core with multiple reactive sites, as well as a diblock copolymer containing hydrophobic polymerized camptothecin (PCPT) prodrug chain and hydrophilic poly[(ethylene glycol) methyl ether methacrylate] (OEGMA) chain. A family of CCP polymeric prodrugs with different drug loading contents (up to 25%) and various sizes of unimolecular micelles (UMs) (around 30 nm) were obtained by adjusting the block ratio of PCPTXX and POEGMA. On account of the amphiphilic structure feature, CPP could take shape water-soluble UMs in aqueous medium with excellent micellar stability. Under imitatively reductive tumor microenvironment, anticancer drug CPT could rapidly escape from CCP UMs in terms of disulfide bond breakage. However, this behavior is strongly refrained in the physiological environment. In vitro and in vivo outcome confirmed that CCP UMs showed excellent performance of sufficient tumor accumulation, high-efficiency tumor growth inhibition and low-toxicity for healthy tissues. Based on these gratifying therapeutic efficacy, it is believed that as-present starburst prodrug strategy can offer a brand-new insight for high-efficiency therapeutic nanoplatforms for chemotherapy application.


Assuntos
Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos , Micelas , Polímeros/química , Pró-Fármacos/química , Animais , Antineoplásicos/química , Camptotecina/administração & dosagem , Camptotecina/química , Feminino , Células HeLa , Humanos , Interações Hidrofóbicas e Hidrofílicas , Células MCF-7 , Camundongos Endogâmicos BALB C , Camundongos Nus , Microambiente Tumoral , beta-Ciclodextrinas/química
17.
Biomacromolecules ; 20(7): 2637-2648, 2019 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-31141665

RESUMO

The physicochemical properties of nanomedicine can be altered with a tumor microenvironment, which influence the precise delivery of drug molecules to the lesion. Thus, the therapeutic efficiency is restrained. Here, a covalent self-assembled nanomicelle (CSNM) based starburst polyprodrug was constructed with the unimolecular micelle-templated self-assembly method and was expected to overcome biological barriers. It aimed to enhance the tumor penetration and chemotherapy efficiency of drugs. In CSNM, a hydrophilic copolymer was glued around a camptothecin (CPT) linked starburst polymeric prodrug [ß-CD-P (CPT- co-NH2)] for protecting the positive charge of the prodrug with a reduction-triggered reversibility in conjugation and activity. Then, the complex was tracelessly delivered into a negatively charged cell membrane, leading to enhanced cellular uptake. Finally, the disulfide bond in the CPT prodrug can be broken under the reductive microenvironment within tumor cells and liberated the CPT molecules. Both in vitro and in vivo results demonstrated the benefits of our CSNM system, including high drug loading, controllable drug release, excellent uptake by tumor cells and remarkable antitumor efficiency. In essence, our findings suggested CSNM as an innovative strategy for drug delivery in chemotherapy, producing a competitive versatility in the development of biomedicine.


Assuntos
Camptotecina , Micelas , Nanoestruturas , Neoplasias Experimentais , Pró-Fármacos , Microambiente Tumoral/efeitos dos fármacos , Animais , Camptotecina/química , Camptotecina/farmacocinética , Camptotecina/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Células HeLa , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanoestruturas/química , Nanoestruturas/uso terapêutico , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Pró-Fármacos/química , Pró-Fármacos/farmacocinética , Pró-Fármacos/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Biomacromolecules ; 20(1): 401-411, 2019 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-30485741

RESUMO

Functionalized nanomaterials with near-infrared (NIR) responsive capacity are quite promising for theranostic treatment of tumors, but formation of NIR responsive nanomaterials with enhanced theranostic ability and excellent biocompatibility is still very challenging. Herein, PEGylated indocyanine green (ICG)-loaded polypyrrole nanoparticles (PPI NPs) were designed and successfully formed through selecting polydopamine as the linkage between each component, demonstrating enhanced NIR responsive theranostic ability against tumor. By combining in vitro cell study with in vivo assay, the formed PPI NPs were proven to be fantastically biocompatible while effectively internalization in HeLa cells and retention in HeLa tumor were demonstrated by in vitro flow cytometry/confocal measurement and in vivo photoacoustic imaging assay. With the guidance of photoacoustic imaging, successful photothermal ablation of tumor was achieved by treatment with PPI NPs plus laser, which was much more effective than the group treated with NPs free of ICG. The combined enhanced photoacoustic and photothermal effect is mainly ascribed to the functionalized polypyrrole nanoparticles, which could accumulate in the tumor site more effectively with a relatively longer retention time taking advantage of the nanomaterial-induced endothelial leakiness phenomenon. All these results demonstrating that this designed PPI NPs possessing enhanced NIR responsive property hold great promise for tumor NIR theranostic applications.


Assuntos
Hipertermia Induzida/métodos , Nanopartículas/química , Neoplasias Experimentais/terapia , Técnicas Fotoacústicas/métodos , Fototerapia/métodos , Animais , Células HeLa , Humanos , Verde de Indocianina/química , Indóis/química , Raios Infravermelhos/uso terapêutico , Camundongos , Camundongos Nus , Nanopartículas/efeitos adversos , Nanopartículas/uso terapêutico , Neoplasias Experimentais/diagnóstico por imagem , Polietilenoglicóis/química , Polímeros/química , Pirróis/química
19.
Nanomedicine ; 17: 1-12, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30654184

RESUMO

Taking advantage of the mesoporous structure of bismuth sulfide nanostars (Bi2S3 NSs), a chemotherapeutic drug of doxorubicin (DOX) and a photosensitizer of chlorin e6 (Ce6) were concurrently loaded in the PEGylated Bi2S3 NSs to formulate a multifunctional nanocomplex (BPDC NSs) for tumor theranostics. BPDC NSs have excellent photothermal conversion efficiency and a capacity of yielding reactive oxygen species (ROS) upon laser irradiation, and can realize on-demand drug release by either pH-activation or thermal induction. Accumulation of the nanodrug could be monitored in real-time by infrared thermal imaging, fluorescence imaging and computed tomography (CT). More importantly, the combination effects of photothermal therapy (PTT), photodynamic therapy (PDT) and chemotherapy were demonstrated to dramatically suppress solid tumors without recurrence in vivo. Featuring low systemic toxicity and high biocompatibility, this nanoplatform could be a promising derivative of Bi2S3 NSs for imaging-guided theranostics of cancer.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Fármacos Fotossensibilizantes/administração & dosagem , Porfirinas/administração & dosagem , Animais , Antibióticos Antineoplásicos/uso terapêutico , Bismuto/uso terapêutico , Linhagem Celular Tumoral , Clorofilídeos , Preparações de Ação Retardada/uso terapêutico , Doxorrubicina/uso terapêutico , Hipertermia Induzida , Camundongos , Nanopartículas/uso terapêutico , Nanopartículas/ultraestrutura , Imagem Óptica , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Polietilenoglicóis/uso terapêutico , Porosidade , Porfirinas/uso terapêutico , Sulfetos/uso terapêutico , Nanomedicina Teranóstica , Tomografia Computadorizada por Raios X
20.
Sensors (Basel) ; 19(22)2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31766178

RESUMO

There are a huge number, and abundant types, of microalgae in the ocean; and most of them have various values in many fields, such as food, medicine, energy, feed, etc. Therefore, how to identify and separation of microalgae cells quickly and effectively is a prerequisite for the microalgae research and utilization. Herein, we propose a microfluidic system that comprised microalgae cell separation, treatment and viability characterization. Specifically, the microfluidic separation function is based on the principle of deterministic lateral displacement (DLD), which can separate various microalgae species rapidly by their different sizes. Moreover, a concentration gradient generator is designed in this system to automatically produce gradient concentrations of chemical reagents to optimize the chemical treatment of samples. Finally, a single photon counter was used to evaluate the viability of treated microalgae based on laser-induced fluorescence from the intracellular chlorophyll of microalgae. To the best of our knowledge, this is the first laboratory prototype system combining DLD separation, concentration gradient generator and chlorophyll fluorescence detection technology for fast analysis and treatment of microalgae using marine samples. This study may inspire other novel applications of micro-analytical devices for utilization of microalgae resources, marine ecological environment protection and ship ballast water management.


Assuntos
Separação Celular/instrumentação , Microalgas/citologia , Microfluídica/instrumentação , Sobrevivência Celular , Fluorescência , Movimento , Reologia , Soluções
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