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1.
Biomaterials ; 266: 120474, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33125969

RESUMO

Free radicals were generally regarded as highly reactive, transient and harmful species. In fact, some of the free radicals can also be inactive, long-lived and beneficial for our health. These properties of free radicals provide future possibilities for their application in various fields. Owning to their open-shell electronic structure, free radicals exhibit unique advantages in biomedical applications, such as high reactivity, photoacoustic and photothermal conversion ability, molecular magnetic. In this review, recent progress on free radicals and their applications in cancer theranostics are presented. Typical materials that exhibit controlled generation of free radicals and their applications for photodynamic therapy (PDT), chemodynamic therapy (CDT), sonodynamic therapy (SDT), gas therapy, hypoxic cancer treatment, photothermal therapy (PTT), photoacoustic imaging (PAI) and magnetic resonance imaging (MRI) are summarized and discussed.

2.
Small ; : e2006582, 2020 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-33382206

RESUMO

Glioblastoma is the most common lethal malignant intracranial tumor with a low 5-year survival rate. Currently, the maximal safe surgical resection, followed by high-dose radiotherapy (RT), is a standard treatment for glioblastoma. However, high-dose radiation to the brain is associated with brain injury and results in a high fatality rate. Here, integrated pharmaceutics (named D-iGSNPs) composed of gold sub-nanometer particles (GSNPs), blood-brain barrier (BBB) penetration peptide iRGD, and cell cycle regulator α-difluoromethylornithine is designed. In both simulated BBB and orthotopic murine GL261 glioblastoma models, D-iGSNPs are proved to have a beneficial effect on the BBB penetration and tumor targeting. Meanwhile, data from cell and animal experiments reveal that D-iGSNPs are able to sensitize RT. More importantly, the synergy of D-iGSNPs with low-dose RT can exhibit an almost equal therapeutic effect with that of high-dose RT. This study demonstrates the therapeutic advantages of D-iGSNPs in boosting RT, and may provide a facile approach to update the current treatment of glioblastoma.

3.
Chem Soc Rev ; 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33226037

RESUMO

Cell primitive-based functional materials that combine the advantages of natural substances and nanotechnology have emerged as attractive therapeutic agents for cancer therapy. Cell primitives are characterized by distinctive biological functions, such as long-term circulation, tumor specific targeting, immune modulation etc. Moreover, synthetic nanomaterials featuring unique physical/chemical properties have been widely used as effective drug delivery vehicles or anticancer agents to treat cancer. The combination of these two kinds of materials will catalyze the generation of innovative biomaterials with multiple functions, high biocompatibility and negligible immunogenicity for precise cancer therapy. In this review, we summarize the most recent advances in the development of cell primitive-based functional materials for cancer therapy. Different cell primitives, including bacteria, phages, cells, cell membranes, and other bioactive substances are introduced with their unique bioactive functions, and strategies in combining with synthetic materials, especially nanoparticulate systems, for the construction of function-enhanced biomaterials are also summarized. Furthermore, foreseeable challenges and future perspectives are also included for the future research direction in this field.

4.
Nat Commun ; 11(1): 4907, 2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32999289

RESUMO

Global alterations in the metabolic network provide substances and energy to support tumor progression. To fuel these metabolic processes, extracellular matrix (ECM) plays a dominant role in supporting the mass transport and providing essential nutrients. Here, we report a fibrinogen and thrombin based coagulation system to construct an artificial ECM (aECM) for selectively cutting-off the tumor metabolic flux. Once a micro-wound is induced, a cascaded gelation of aECM can be triggered to besiege the tumor. Studies on cell behaviors and metabolomics reveal that aECM cuts off the mass transport and leads to a tumor specific starvation to inhibit tumor growth. In orthotopic and spontaneous murine tumor models, this physical barrier also hinders cancer cells from distant metastasis. The in vivo gelation provides an efficient approach to selectively alter the tumor mass transport. This strategy results in a 77% suppression of tumor growth. Most importantly, the gelation of aECM can be induced by clinical operations such as ultrasonic treatment, surgery or radiotherapy, implying this strategy is potential to be translated into a clinical combination regimen.


Assuntos
Materiais Biomiméticos/administração & dosagem , Matriz Extracelular/química , Neoplasias/terapia , Animais , Transporte Biológico/efeitos dos fármacos , Transporte Biológico/efeitos da radiação , Materiais Biomiméticos/química , Materiais Biomiméticos/efeitos da radiação , Linhagem Celular Tumoral/transplante , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Quimiorradioterapia/métodos , Modelos Animais de Doenças , Matriz Extracelular/metabolismo , Matriz Extracelular/efeitos da radiação , Feminino , Fibrinogênio/administração & dosagem , Fibrinogênio/química , Fibrinogênio/efeitos da radiação , Géis , Humanos , Injeções Intravenosas , Metabolômica , Camundongos , Neoplasias/metabolismo , Trombina/administração & dosagem , Trombina/química , Trombina/efeitos da radiação , Terapia por Ultrassom/métodos , Ondas Ultrassônicas
5.
Adv Drug Deliv Rev ; 160: 36-51, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33080257

RESUMO

Controlled nano-systems for drug delivery are designed to deliver therapeutical drugs to desirable sites on demand. Due to the diverse physiological functions of peptides, it is reasonable to introduce peptides into anti-tumor nano-system. The integration of peptides into nanomaterials has complementary advantages, which not only avoids the rapid degradation of peptides in vivo, but also improves the intelligence and functionality of the nano-system. We summarized the functional peptides with targeting and stimulus-responsive properties, and the present review outlined the most relevant and recent developed peptide-based multifunctional nanomaterials for tumor therapy.

6.
Phytother Res ; 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33006176

RESUMO

Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects not only joints but also multiple organ systems including cardiovascular system. Endothelial dysfunction plays an important role in cardiovascular diseases (CVD). In RA, endothelial dysfunction exists at both the macrovascular and the microvascular levels, which is a precursor to vasculitis. This study aimed to investigate the pathogenesis of vasculitis and the therapeutic effect of CP-25 on vasculitis in high-fat diet (HFD) collagen-induced arthritis (CIA) rats. Experimental groups were divided into normal group, HFD group, CIA group, HFD CIA group, CP-25 group and MTX group. In vitro, IL-17A was used to stimulate human umbilical vein endothelial cells (HUVECs), and then CP-25 was used to intervene. Results showed that CP-25 reduced global scoring (GS), arthritis index (AI), and swollen joint count (SJC) scores, improved histopathological score, reduced T cells percentage, and decreased IL-17A and ICAM-1 levels. Besides, CP-25 reduced the expression of p-STAT3 to normal levels in vascular of HFD CIA rats. In vitro, IL-17A promoted the expression of p-JAK1, p-JAK2, p-JAK3, pSTAT3, and ICAM-1, and CP-25 inhibited the expression of p-JAK1, p-JAK2, p-JAK3, p-STAT3, and ICAM-1. In conclusion, CP-25 might inhibit endothelial cell activation through inhibiting IL-17A/JAK/STAT3 signaling pathway, which improves vasculitis in HFD CIA rats.

7.
Adv Mater ; 32(45): e2004529, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33006175

RESUMO

While microbial-based therapy has been considered as an effective strategy for treating diseases such as colon cancer, its safety remains the biggest challenge. Here, probiotics and prebiotics, which possess ideal biocompatibility and are extensively used as additives in food and pharmaceutical products, are combined to construct a safe microbiota-modulating material. Through the host-guest chemistry between commercial Clostridium butyricum and chemically modified prebiotic dextran, prebiotics-encapsulated probiotic spores (spores-dex) are prepared. It is found that spores-dex can specifically enrich in colon cancers after oral administration. In the lesion, dextran is fermented by C. butyricum, and thereby produces anti-cancer short-chain fatty acids (SCFAs). Additionally, spores-dex regulate the gut microbiota, augment the abundance of SCFA-producing bacteria (e.g., Eubacterium and Roseburia), and markedly increase the overall richness of microbiota. In subcutaneous and orthotopic tumor models, drug-loaded spores-dex inhibit tumor growth up to 89% and 65%, respectively. Importantly, no obvious adverse effect is found. The work sheds light on the possibility of using a highly safe strategy to regulate gut microbiota, and provides a promising avenue for treating various gastrointestinal diseases.

8.
Sci Adv ; 6(22): eaaz4107, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32766439

RESUMO

Platelets play a critical role in the regulation of coagulation, one of the essential processes in life, attracting great attention. However, mimicking platelets for in vivo artificial coagulation is still a great challenge due to the complexity of the process. Here, we design platelet-like nanoparticles (pNPs) based on self-assembled peptides that initiate coagulation and form clots in blood vessels. The pNPs first bind specifically to a membrane glycoprotein (i.e., CD105) overexpressed on angiogenetic endothelial cells in the tumor site and simultaneously transform into activated platelet-like nanofibers (apNFs) through ligand-receptor interactions. Next, the apNFs expose more binding sites and recruit and activate additional pNPs, forming artificial clots in both phantom and animal models. The pNPs are proven to be safe in mice without systemic coagulation. The self-assembling peptides mimic platelets and achieve artificial coagulation in vivo, thus providing a promising therapeutic strategy for tumors.

9.
Angew Chem Int Ed Engl ; 59(48): 21562-21570, 2020 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-32779303

RESUMO

By leveraging the ability of Shewanella oneidensis MR-1 (S. oneidensis MR-1) to anaerobically catabolize lactate through the transfer of electrons to metal minerals for respiration, a lactate-fueled biohybrid (Bac@MnO2 ) was constructed by modifying manganese dioxide (MnO2 ) nanoflowers on the S. oneidensis MR-1 surface. The biohybrid Bac@MnO2 uses decorated MnO2 nanoflowers as electron receptor and the tumor metabolite lactate as electron donor to make a complete bacterial respiration pathway at the tumor sites, which results in the continuous catabolism of intercellular lactate. Additionally, decorated MnO2 nanoflowers can also catalyze the conversion of endogenous hydrogen peroxide (H2 O2 ) into generate oxygen (O2 ), which could prevent lactate production by downregulating hypoxia-inducible factor-1α (HIF-1α) expression. As lactate plays a critical role in tumor development, the biohybrid Bac@MnO2 could significantly inhibit tumor progression by coupling bacteria respiration with tumor metabolism.

10.
ACS Nano ; 14(8): 9848-9860, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32658459

RESUMO

Metal carbonyl complexes can readily liberate carbon monoxide (CO) in response to activation stimulus. However, applicability of metal carbonyl complexes is limited because they are unstable under natural ambient conditions of moisture and oxygen. Reported here is the rational design of an iron carbonyl complex delivery nanosystem for the improvement of cancer therapy. We demonstrated that iron pentacarbonyl (Fe(CO)5) can be encapsulated into the cavity of a Au nanocage under an oxygen-free atmosphere and then controllably form iron oxide on the surface of the Au nanocage under aerobic conditions. The formation of iron oxide efficiently avoids the leakage and oxidation of the caged Fe(CO)5. The resulting nanomaterial exhibits excellent safety, biocompatibility, and stability, which can be specifically activated under near-infrared (NIR) irradiation within the tumor environment to generate CO and iron. The released CO causes damage to mitochondria and subsequent initiation of autophagy. More importantly, during autophagy, the nanomaterial that contains iron and iron oxide can accumulate into the autolysosome and result in its destruction. The produced CO and iron show excellent synergistic effects in cancer cells.

11.
Nat Biomed Eng ; 4(9): 853-862, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32632226

RESUMO

Patients with kidney failure commonly require dialysis to remove nitrogenous wastes and to reduce burden to the kidney. Here, we show that a bacterial cocktail orally delivered in animals with kidney injury can metabolize blood nitrogenous waste products before they diffuse through the intestinal mucosal barrier. The microbial cocktail consists of three strains of bacteria isolated from faecal microbiota that metabolize urea and creatinine into amino acids, and is encapsulated in calcium alginate microspheres coated with a polydopamine layer that is selectively permeable to small-molecule nitrogenous wastes. In murine models of acute kidney injury and chronic kidney failure, and in porcine kidney failure models, the encapsulated microbial cocktail significantly reduced urea and creatinine concentrations in blood, and did not lead to any adverse effects.


Assuntos
Enteroadsorção/métodos , Microbiota , Compostos de Nitrogênio/isolamento & purificação , Insuficiência Renal/terapia , Administração Oral , Alginatos/química , Amônia/metabolismo , Animais , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/metabolismo , Cápsulas/administração & dosagem , Cápsulas/química , Creatinina/metabolismo , Modelos Animais de Doenças , Fezes/microbiologia , Indóis/química , Camundongos , Microfluídica , Microesferas , Compostos de Nitrogênio/metabolismo , Polímeros/química , Suínos , Resultado do Tratamento , Ureia/metabolismo
12.
Angew Chem Int Ed Engl ; 59(41): 18078-18086, 2020 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-32648640

RESUMO

Multi-component MOFs contain multiple sets of unique and hierarchical pores, with different functions for different applications, distributed in their inter-linked domains. Herein, we report the construction of a class of precisely aligned flexible-on-rigid hybrid-phase MOFs with a unique rods-on-octahedron morphology. We demonstrated that hybrid-phase MOFs can be constructed based on two prerequisites: the partially matched topology at the interface of the two frameworks, and the structural flexibility of MOFs with acs topology, which can compensate for the differences in lattice parameters. Furthermore, we achieved domain selective loading of multiple guest molecules into the hybrid-phase MOF, as observed by scanning transmission electron microscopy-energy-dispersive X-ray spectrometry elemental mapping. Most importantly, we successfully applied the constructed hybrid-phase MOF to develop a dual-drug delivery system with controllable loading ratio and release kinetics.

13.
Sci Adv ; 6(23): eabb0020, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32548273

RESUMO

Although vascular disrupting agents (VDAs) have been extensively implemented in current clinical tumor therapy, the notable adverse events caused by long-term dosing severely limit the therapeutic efficacy. To improve this therapy, we report a strategy for VDA-induced aggregation of gold nanoparticles to further destroy tumor vascular by photothermal effect. This strategy could effectively disrupt tumor vascular and cut off the nutrition supply after just one treatment. In the murine tumor model, this strategy results in notable tumor growth inhibition and gives rise to a 92.7% suppression of tumor growth. Besides, enhanced vascular damage could also prevent cancer cells from distant metastasis. Moreover, compared with clinical therapies, this strategy still exhibits preferable tumor suppression and metastasis inhibition ability. These results indicate that this strategy has great potential in tumor treatment and could effectively enhance tumor vascular damage and avoid the side effects caused by frequent administration.

14.
Sci Adv ; 6(20): eaba1590, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32440552

RESUMO

Mounting evidence suggests that the gut microbiota contribute to colorectal cancer (CRC) tumorigenesis, in which the symbiotic Fusobacterium nucleatum (Fn) selectively increases immunosuppressive myeloid-derived suppressor cells (MDSCs) to hamper the host's anticancer immune response. Here, a specifically Fn-binding M13 phage was screened by phage display technology. Then, silver nanoparticles (AgNP) were assembled electrostatically on its surface capsid protein (M13@Ag) to achieve specific clearance of Fn and remodel the tumor-immune microenvironment. Both in vitro and in vivo studies showed that of M13@Ag treatment could scavenge Fn in gut and lead to reduction in MDSC amplification in the tumor site. In addition, antigen-presenting cells (APCs) were activated by M13 phages to further awaken the host immune system for CRC suppression. M13@Ag combined with immune checkpoint inhibitors (α-PD1) or chemotherapeutics (FOLFIRI) significantly prolonged overall mouse survival in the orthotopic CRC model.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32374492

RESUMO

Nanotheranostic agents (NTAs) that integrate diagnostic capabilities and therapeutic functions have great potential for personalized medicine, yet poor tumor specificity severely restricts further clinical applications of NTAs. Here, a pro-NTA (precursor of nanotheranostic agent) activation strategy is reported for in situ NTA synthesis at tumor tissues to enhance the specificity of tumor therapy. This pro-NTA, also called PBAM, is composed of an MIL-100 (Fe)-coated Prussian blue (PB) analogue (K2 Mn[Fe(CN)6 ]) with negligible absorption in the near-infrared region and spatial confinement of Mn2+ ions. In a mildly acidic tumor microenvironment (TME), PBAM can be specifically activated to synthesize the photothermal agent PB nanoparticles, with release of free Mn2+ ions due to the internal fast ion exchange, resulting in the "ON" state of both T1 -weighted magnetic resonance imaging and photoacoustic signals. In addition, the combined Mn2+ -mediated chemodynamic therapy in the TME and PB-mediated photothermal therapy guarantee a more efficient therapeutic performance compared to monotherapy. In vivo data further show that the pro-NTA activation strategy could selectively brighten solid tumors and detect invisible lymph node metastases with high specificity.

16.
Nat Commun ; 11(1): 1985, 2020 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-32332752

RESUMO

The unsatisfactory response rate of immune checkpoint blockade (ICB) immunotherapy severely limits its clinical application as a tumor therapy. Here, we generate a vaccine-based nanosystem by integrating siRNA for Cd274 into the commercial human papillomavirus (HPV) L1 (HPV16 L1) protein. This nanosystem has good biosafety and enhances the therapeutic response rate of anti-tumor immunotherapy. The HPV16 L1 protein activates innate immunity through the type I interferon pathway and exhibits an efficient anti-cancer effect when cooperating with ICB therapy. For both resectable and unresectable breast tumors, the nanosystem decreases 71% tumor recurrence and extends progression-free survival by 67%. Most importantly, the nanosystem successfully induces high response rates in various genetically modified breast cancer models with different antigen loads. The strong immune stimulation elicited by this vaccine-based nanosystem might constitute an approach to significantly improve current ICB immunotherapy.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/terapia , Vacinas Anticâncer/administração & dosagem , Imunoterapia/métodos , Nanopartículas/administração & dosagem , Animais , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/genética , Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Vacinas Anticâncer/genética , Vacinas Anticâncer/imunologia , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/imunologia , Linhagem Celular Tumoral/transplante , Modelos Animais de Doenças , Feminino , Técnicas de Silenciamento de Genes , Células HEK293 , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/imunologia , Humanos , Imunidade Inata/genética , Camundongos , Recidiva Local de Neoplasia , Proteínas Oncogênicas Virais/genética , Proteínas Oncogênicas Virais/imunologia , Intervalo Livre de Progressão , RNA Interferente Pequeno/genética , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/genética , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia
17.
Nanoscale ; 12(16): 8890-8897, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32266902

RESUMO

Selectively attenuating the protection offered by heat shock protein 90 (HSP90), which is indispensable for the stabilization of the essential regulators of cell survival and works as a cell guardian under oxidative stress conditions, is a potential approach to improve the efficiency of cancer therapy. Here, we designed a biodegradable nanoplatform (APCN/BP-FA) based on a Zr(iv)-based porphyrinic porous coordination network (PCN) and black phosphorus (BP) sheets for efficient photodynamic therapy (PDT) by enhancing the accumulation of the nanoplatforms in the tumor area and attenuating the protection of cancer cells. Owing to the favorable degradability of BP, the nanosystem exhibited accelerated the release of the HSP90 inhibitor tanespimycin (17-AAG) and an apparent promotion in the reactive oxygen species (ROS) yield of PCN as well as expedited the degradation of the PCN-laden BP nanoplatforms. Both in vitro and in vivo results revealed that the elevated amounts of ROS and reduced cytoprotection in tumor cells were caused by the nanoplatforms. This strategy may provide a promising method for attenuating cytoprotection to aid efficient photodynamic therapy.

18.
Biomaterials ; 248: 120029, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32289589

RESUMO

Although metal-based agents are widely used in disease treatment, precisely controlled metal ions release is still a challenge. Here, we demonstrated a nanoplatform (PAM) to achieve on-demand activation and release of metal ions via controlling oxidation condition by near infrared (NIR) light-inducted photodynamic therapy (PDT). PAM was constructed by decorating silver nanoparticles (AgNPs) onto the porphyrinic porous coordination network (PCN) and further camouflaging with the neutrophil membrane (NM) with inflammatory targeting ability. PAM was inactive without irradiation, causing no damage to normal tissues. However, under NIR irradiation at tumor or infected tissues, PCN locally generated singlet oxygen (1O2), enabling AgNPs to be partly degraded to release cytotoxic Ag+ for metal ions therapy (MIT). Simultaneously, the incorporated AgNPs promoted the 1O2 yield of PCN due to the localized electric field effect. Consequently, the NIR light-controlled interlocking interactions between AgNPs and PCN might offer a great potential for achieving controlled, precise and efficient disease treatment with reduced side-effect.

19.
Biomaterials ; 245: 119986, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32229331

RESUMO

Diabetes is an increasing health problem and associated with inflammatory complications that seriously affects the quality of life and survival of patients. Carbon monoxide (CO), owing to its anti-inflammatory and anti-apoptotic properties, has become a potential therapeutic molecule for the treatment of autoimmune diseases. Here, we constructed a mesoporous silica-based biomimetic CO nanogenerator (mMMn), which was loaded with manganese carbonyl and camouflaged with macrophage membrane. Driven by the active targeting of macrophage membrane to inflammatory sites, the as-designed mMMn could effectively accumulate in pancreatic tissue of type 1 diabetic mice, which was established by consecutive administration of streptozotocin (STZ). It was found that the local reactive oxygen species (ROS) within pancreas could trigger the continuous CO release from mMMn, which greatly ameliorated diabetes in mice with improved blood glucose homeostasis by alleviating inflammatory responses and inhibiting ß-cells apoptosis. The exogenous CO targeting to pancreatic tissue paves a novel way for the treatment of type 1 diabetes.

20.
Chemistry ; 26(70): 16568-16581, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32320099

RESUMO

Covalent organic frameworks (COFs) are an emerging kind of crystalline porous polymers that present the precise integration of organic building blocks into extensible structures with regular pores and periodic skeletons. The diversity of organic units and covalent linkages makes COFs a rising materials platform for the design of structure and functionality. Herein, recent research progress in developing COFs for photoluminescent materials is summarised. Structural and functional design strategies are highlighted and fundamental problems that need to be solved are identified, in conjunction with potential applications from perspectives of photoluminescent materials.

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