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1.
ACS Nano ; 14(3): 3259-3271, 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32049490

RESUMO

The cancer cell membrane contains an arsenal of highly specific homotypic moieties that can be used to recognize its own kind. These cell membranes are often used to coat spherical nanoparticles to enhance nanomedicines' targeting specificities and uptakes. A sphere, however, has only a point contact with a surface at any given time. It is shown here that, by retaining a flatter morphology of the cracked cell membrane through stiffening with in situ synthesized gold nanomaterials, an increased area of interaction could be maintained and hence improve upon the in vitro and in vivo homotypic targeting capabilities between cancer cell types. This enhancement is especially important in vivo as any nanomedicine with targeting moieties probably has a single pass at interacting with the target cell before subsequent system clearance. Possible future clinical applications may involve the usage of a patient's autologous tumor biopsy tissues, which are very limited in supply, and therefore ensuring that we capitalize on the entire collective surface area of the cancer cell membrane available becomes an important consideration in the design and delivery our cell membrane-derived nanomedicines.

2.
J Control Release ; 320: 159-167, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31978443

RESUMO

Glucose-responsive insulin delivery system mimicking the function of pancreatic ß-cells to maintain blood glucose homeostasis would effectively alleviate diabetes. Here, a new glucose-responsive delivery (ZIF@Ins&GOx) for self-regulated insulin release was constructed by encapsulating insulin and glucose oxidase (GOx) into pH-sensitive zeolitic imidazole framework-8 (ZIF-8) nanocrystals. After entering the cavities of ZIF-8, glucose can be oxidized into gluconic acid by GOx, causing a decrease in local pH. Then, ZIF-8 nanocrystals would be degraded under the acidic microenvironment that in turn triggers the release of insulin in a glucose responsive fashion. In vitro studies indicated that the biological activity of insulin could be protected by the rigid structure of ZIF-8 and the release of insulin could be modulated in response to glucose concentrations. In vivo experiments demonstrated that a single subcutaneous injection of the ZIF@Ins&GOx would facilitate the stabilization of blood glucose level of normoglycemic state for up to 72 h in type 1 diabetes (T1D). The multifunctional insulin delivery system shows a new proof-of-concept for T1D treatment by using ZIF-8 nanocrystals loaded with insulin and enzyme.

3.
ACS Nano ; 13(12): 14230-14240, 2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31714733

RESUMO

Tumorous vasculature plays key roles in sustaining tumor growth. Vascular disruption is accompanied by internal coagulation along with platelet recruitment and the resulting suppression of oxygen supply. We intend to artificially create this physiological process to establish the mutual feedback between vascular disruption and platelet-mimicking biotaxis for the cascade amplification of hypoxia-dependent therapy. To prove this concept, mesoporous silica nanoparticles are co-loaded with a hypoxia-activated prodrug (HAP) and a vessel-disruptive agent and then coated with platelet membranes. Upon entering into tumors, our nanotherapeutic can disrupt local vasculature for tumor inhibition. This platelet membrane-coated nanoplatform shares the hemorrhage-tropic function with parental platelets and can be persistently recruited by the vasculature-disrupted tumors. In this way, the intratumoral vascular disruption and tumor targeting are biologically interdependent and mutually reinforced. Relying on this mutual feedback, tumorous hypoxia was largely promoted by more than 20-fold, accounting for the effective recovery of the HAP's cytotoxicity. Consequently, our bioinspired nanodesign has demonstrated highly specific and effective antitumor potency via the biologically driven cooperation among intratumoral vascular disruption, platelet-mimicking biotaxis, cascade hypoxia amplification, and hypoxia-sensitive chemotherapy. This study offers a paradigm of correlating the therapeutic design with the physiologically occurring events to achieve better therapy performance.

4.
Adv Sci (Weinh) ; 6(17): 1900835, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31508286

RESUMO

Metal ions are of significant importance in biomedical science. This study reports a new concept of cytomembrane-mediated biospecific transport of metal ions without using any other materials. For the first time, cytomembranes are exploited for two-step conjugation with metal ions to provide hybrid nanomaterials. The innate biofunction of cell membranes renders the hybrids with superior advantages over common vehicles for metal ions, including excellent biocompatibility, low immunogenic risk, and particularly specific biotargeting functionality. As a proof-of-concept demonstration, cancer cell membranes are used for in vivo delivery of various metal ions, including ruthenium, europium, iron, and manganese, providing a series of tumor-targeted nanohybrids capable of photothermal therapy/imaging, magnetic resonance imaging, photoacoustic imaging, and fluorescence imaging with improved performances. In addition, the special structure of the cell membrane allows easy accommodation of small-molecular agents within the nanohybrids for effective chemotherapy. This study provides a new class of metal-ion-included nanomaterials with versatile biofunctions and offers a novel solution to address the important challenge in the field of in vivo targeted delivery of metal ions.

5.
Adv Mater ; 31(15): e1807211, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30803083

RESUMO

To engineer patient-derived cells into therapy-purposed biologics is a promising solution to realize personalized treatments. Without using gene-editing technology, a live cell-typed therapeutic is engineered for tumor treatment by artificially reprogramming macrophages with hyaluronic acid-decorated superparamagnetic iron oxide nanoparticles (HIONs). This nanoparticle-assisted cell-reprogramming strategy demonstrates profound advantages, due to the combined contributions from the biological regulation of HIONs and the intrinsic nature of macrophages. Firstly, the reprogrammed macrophages present a substantial improvement in their innate capabilities, such as more effective tumor targeting and more efficient generation of bioactive components (e.g., reactive oxygen species, bioactive cytokines) to suppress tumor growth. Furthermore, this cell therapeutic exhibits cytostatic/proapoptotic effects specific to cancer cells. Secondly, HIONs enable macrophages more resistant to the intratumoral immunosuppressive environment. Thirdly, the macrophages are endowed with a strong ability to prime in situ protumoral M2 macrophages into antitumor M1 phenotype in a paracrine-like manner. Consequently, a synergistic tumor-inhibition effect is achieved. This study shows that engineering nanomaterial-reprogrammed live cells as therapeutic biologics may be a more preferable option to the commonly used approaches where nanomaterials are administrated to induce bioresponse of certain cells in vivo.


Assuntos
Reprogramação Celular , Macrófagos/metabolismo , Animais , Antígenos de Neoplasias/imunologia , Linhagem Celular Tumoral , Citotoxicidade Imunológica , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Macrófagos/imunologia , Nanopartículas de Magnetita , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/imunologia , Neoplasias/terapia , Microambiente Tumoral/imunologia
6.
ACS Nano ; 13(2): 1784-1794, 2019 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-30698953

RESUMO

Hypoxia, a ubiquitously aberrant phenomenon implicated in tumor growth, causes severe tumor resistance to therapeutic interventions. Instead of the currently prevalent solution through intratumoral oxygen supply, we put forward an "O2-economizer" concept by inhibiting the O2 consumption of cell respiration to spare endogenous O2 and overcome the hypoxia barrier. A nitric oxide (NO) donor responsible for respiration inhibition and a photosensitizer for photodynamic therapy (PDT) are co-loaded into poly(d,l-lactide- co-glycolide) nanovesicles to provide a PDT-specific O2 economizer. Once accumulating in tumors and subsequently responding to the locally reductive environment, the carried NO donor undergoes breakdown to produce NO for inhibiting cellular respiration, allowing more O2 in tumor cells to support the profound enhancement of PDT. Depending on the biochemical reallocation of cellular oxygen resource, this O2-economizer concept offers a way to address the important issue of hypoxia-induced tumor resistance to therapeutic interventions, including but not limited to PDT.

7.
ACS Nano ; 12(12): 12181-12192, 2018 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-30458111

RESUMO

Non-apoptotic ferroptosis is of clinical importance because it offers a solution to the inevitable biocarriers of traditional apoptotic therapeutic means. Inspired by industrial electro-Fenton technology featured with electrochemical iron cycling, we construct ferrous-supply-regeneration nanoengineering to intervene tumorous iron metabolism for enhanced ferroptosis. Fe3+ ion and naturally derived tannic acid (TA) spontaneously form a network-like corona onto sorafenib (SRF) nanocores. The formed SRF@FeIIITA nanoparticles can respond to a lysosomal acid environment with corona dissociation, permitting SRF release to inhibit GPX4 enzyme for ferroptosis initiation. TA is arranged to chemically reduce the liberated and the ferroptosis-generated Fe3+ to Fe2+, offering iron redox cycling to, thus, effectively produce lipid peroxide required in ferroptosis. Sustained Fe2+ supply leads to long-term cytotoxicity, which is identified to be specific to H2O2-overloaded cancer cells but minimal in normal cells. SRF@FeIIITA-mediated cell death proves to follow the ferroptosis pathway and strongly inhibits tumor proliferation. Moreover, SRF@FeIIITA provides a powerful platform capable of versatile integration between apoptosis and non-apoptosis means. Typically, photosensitizer-adsorbed SRF@FeIIITA demonstrates rapid tumor imaging owing to the acid-responsive fluorescence recovery. Together with ferroptosis, imaging-guided photodynamic therapy induces complete tumor elimination. This study offers ideas about how to advance anticancer ferroptosis through rational material design.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Nanotecnologia , Neoplasias/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Células 3T3 , Animais , Antineoplásicos/química , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/diagnóstico por imagem , Fármacos Fotossensibilizantes/química
8.
Small ; 14(50): e1803602, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30370690

RESUMO

By integrating the characteristics of each therapy modality and material chemistry, a multitherapy modality is put forward: tumor starvation triggered synergism with sensitized chemotherapy. Following starvation-induced amplification of pathological abnormalities in tumors, chemotherapy is arranged to be locally activated and accurately reinforced to perfect multitherapy synergism from spatial and temporal perspectives. To this end, glucose oxidase (GOD) and a hypoxic prodrug of tirapazamine (TPZ) are loaded in acidity-decomposable calcium carbonate (CaCO3 ) nanoparticles concurrently tethered by hyaluronic acid. This hybrid nanotherapeutic shows a strong tendency to accumulate in tumors postinjection due to the cooperation between passive and active targeting mechanisms. The GOD-driven oxidation reaction deprives tumors of glucose for starvation therapy and concomitantly induces tumorous abnormality amplifications including elevated acidity and exacerbated hypoxia. Programmatically, the acidity amplification causes CaCO3 decomposition, offering not only spatial control over the liberation of embedded TPZ just within tumors but also the temporal control over timely chemotherapy initiation to match the occurrence of hypoxia amplification and thus benefiting perfect synergism between starvation therapy and chemotherapy.


Assuntos
Antineoplásicos/química , Carbonato de Cálcio/química , Nanopartículas/química , Pró-Fármacos/química , Tirapazamina/química , Glucose Oxidase/metabolismo , Ácido Hialurônico/química
9.
Nano Lett ; 18(11): 6804-6811, 2018 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-30350653

RESUMO

Free radicals have emerged as new-type and promising candidates for hypoxic tumor treatment, and further study of their therapeutic mechanism by real-time imaging is of great importance to explore their biomedical applications. Herein, we present a smart free-radical generator AuNC-V057-TPP for hypoxic tumor therapy; the AuNC-V057-TPP not only exhibits good therapeutic effect under both hypoxic and normoxic conditions but also can monitor the release of free radicals in real-time both in vitro and in vivo. What is more, with the mitochondria-targeting ability, the AuNC-V057-TPP is demonstrated with improved antitumor efficacy through enhanced free radical level in mitochondria, which leads to mitochondrial membrane damage and ATP production reduction and finally induces cancer cell apoptosis.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Radicais Livres/metabolismo , Ouro , Neoplasias Mamárias Animais , Nanopartículas Metálicas , Mitocôndrias , Imagem Molecular/métodos , Hipóxia Tumoral , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Ouro/química , Ouro/farmacologia , Neoplasias Mamárias Animais/diagnóstico por imagem , Neoplasias Mamárias Animais/metabolismo , Neoplasias Mamárias Animais/terapia , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Camundongos , Mitocôndrias/metabolismo , Mitocôndrias/patologia
10.
Adv Mater ; 30(35): e1802006, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30015997

RESUMO

Extreme hypoxia of tumors represents the most notable barrier against the advance of tumor treatments. Inspired by the biological nature of red blood cells (RBCs) as the primary oxygen supplier in mammals, an aggressive man-made RBC (AmmRBC) is created to combat the hypoxia-mediated resistance of tumors to photodynamic therapy (PDT). Specifically, the complex formed between hemoglobin and enzyme-mimicking polydopamine, and polydopamine-carried photosensitizer is encapsulated inside the biovesicle that is engineered from the recombined RBC membranes. The mean corpuscular hemoglobin of AmmRBCs reaches about tenfold as high as that of natural RBCs. Owing to the same origin of outer membranes, AmmRBCs share excellent biocompatibility with parent RBCs. The introduced polydopamine plays the role of the antioxidative enzymes existing inside RBCs to effectively prevent the oxygen-carrying hemoglobin from the oxidation damage during the circulation. This biomimetic engineering can accumulate in tumors, permit in situ efficient oxygen supply, and impose strong PDT efficacy toward the extremely hypoxic tumor with complete tumor elimination. The man-made pseudo-RBC shows potentials as a universal oxygen-self-supplied platform to sensitize hypoxia-limited tumor treatment means, including but not limited to PDT. Meanwhile, this study offers ideas to the production of artificial substitutes of packed RBCs for clinical blood transfusion.


Assuntos
Eritrócitos , Animais , Hipóxia Celular , Oxigênio , Fotoquimioterapia , Fármacos Fotossensibilizantes
11.
Small ; 14(20): e1800292, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29665292

RESUMO

This study reports a double-targeting "nanofirework" for tumor-ignited imaging to guide effective tumor-depth photothermal therapy (PTT). Typically, ≈30 nm upconversion nanoparticles (UCNP) are enveloped with a hybrid corona composed of ≈4 nm CuS tethered hyaluronic acid (CuS-HA). The HA corona provides active tumor-targeted functionality together with excellent stability and improved biocompatibility. The dimension of UCNP@CuS-HA is specifically set within the optimal size window for passive tumor-targeting effect, demonstrating significant contributions to both the in vivo prolonged circulation duration and the enhanced size-dependent tumor accumulation compared with ultrasmall CuS nanoparticles. The tumors featuring hyaluronidase (HAase) overexpression could induce the escape of CuS away from UCNP@CuS-HA due to HAase-catalyzed HA degradation, in turn activating the recovery of initially CuS-quenched luminescence of UCNP and also driving the tumor-depth infiltration of ultrasmall CuS for effective PTT. This in vivo transition has proven to be highly dependent on tumor occurrence like a tumor-ignited explosible firework. Together with the double-targeting functionality, the pathology-selective tumor ignition permits precise tumor detection and imaging-guided spatiotemporal control over PTT operation, leading to complete tumor ablation under near infrared (NIR) irradiation. This study offers a new paradigm of utilizing pathological characteristics to design nanotheranostics for precise detection and personalized therapy of tumors.


Assuntos
Hipertermia Induzida , Nanofibras/química , Neoplasias/patologia , Fototerapia , Animais , Morte Celular , Cobre/química , Células Hep G2 , Humanos , Ácido Hialurônico/química , Hialuronoglucosaminidase/metabolismo , Luminescência , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células NIH 3T3 , Nanofibras/ultraestrutura , Nanopartículas/química , Nanopartículas/ultraestrutura , Células RAW 264.7 , Esferoides Celulares/patologia , Esferoides Celulares/ultraestrutura , Sulfetos/química , Temperatura Ambiente
12.
ACS Appl Mater Interfaces ; 10(17): 15030-15039, 2018 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-29633614

RESUMO

Here, a tumor-targeted MnO2 motor nanosystem (designed as MG/HA) was constructed by the assembly of glucose oxidase (GOD), manganese dioxide (MnO2), and glycoprotein CD44-targeting polymer hyaluronic acid (HA) to elevate cancer-starving therapy efficacy in solid tumor. Upon the specific uptake of MG/HA by CD44 overexpressed cancer cells, GOD catalyzed the oxidation of glucose into gluconic acid and hydrogen peroxide (H2O2) accompanying the consumption of oxygen (O2). Meanwhile, MnO2 would react with H2O2 and acid to generate O2, which is in turn supplied to the glucose-depletion process, running like a loop. As a result, MnO2 is displayed as a motor to promote the rate of glucose depletion that contributed to the starving therapy. In contrast to G/HA, MG/HA could not only achieve effective glucose consumption to depress cancer progression, but also alleviate hypoxia and reduce the expression of Glut1 to inhibit the metabolism for further restraining the tumor aggressiveness and metastasis. The concept of MnO2 motor shows a promising prospect to overcome the restriction of the starving therapy.


Assuntos
Molibdênio/análise , Óxidos/análise , Glucose Oxidase , Ácido Hialurônico , Peróxido de Hidrogênio , Oxirredução , Oxigênio
13.
Adv Mater ; 30(22): e1707459, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29675900

RESUMO

Many viruses have a lipid envelope derived from the host cell membrane that contributes much to the host specificity and the cellular invasion. This study puts forward a virus-inspired technology that allows targeted genetic delivery free from man-made materials. Genetic therapeutics, metal ions, and biologically derived cell membranes are nanointegrated. Vulnerable genetic therapeutics contained in the formed "nanogene" can be well protected from unwanted attacks by blood components and enzymes. The surface envelope composed of cancer cell membrane fragments enables host-specific targeting of the nanogene to the source cancer cells and homologous tumors while effectively inhibiting recognition by macrophages. High transfection efficiency highlights the potential of this technology for practical applications. Another unique merit of this technology arises from the facile combination of special biofunction of metal ions with genetic therapy. Typically, Gd(III)-involved nanogene generates a much higher T1 relaxation rate than the clinically used Gd magnetic resonance imaging agent and harvests the enhanced MRI contrast at tumors. This virus-inspired technology points out a distinctive new avenue for the disease-specific transport of genetic therapeutics and other biomacromolecules.

14.
ACS Nano ; 12(5): 4630-4640, 2018 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-29584395

RESUMO

We report on the benzoporphyrin-based metal-organic framework (TBP-MOF), with 10-connected Zr6 cluster and much improved photophysical properties over the traditional porphyrin-based MOFs. It was found that TBP-MOF exhibited red-shifted absorption bands and strong near-infrared luminescence for bioimaging, whereas the π-extended benzoporphyrin-based linkers of TBP-MOF facilitated 1O2 generation to enhance O2-dependent photodynamic therapy (PDT). It was demonstrated that poly(ethylene glycol)-modified nanoscale TBP-MOF (TBP-nMOF) can be used as an effective PDT agent under hypoxic tumor microenvironment. We also elucidated that the low O2-dependent PDT of TBP-nMOF in combination with αPD-1 checkpoint blockade therapy can not only suppress the growth of primary tumor, but also stimulate an antitumor immune response for inhibiting metastatic tumor growth. We believe this TBP-nMOF has great potential to serve as an efficient photosensitizer for PDT and cancer immunotherapy.


Assuntos
Antineoplásicos/química , Estruturas Metalorgânicas/química , Nanopartículas/química , Metástase Neoplásica/terapia , Fármacos Fotossensibilizantes/química , Porfirinas/química , Zircônio/química , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Antígeno B7-H1/antagonistas & inibidores , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Terapia Combinada , Xenoenxertos , Humanos , Imunoterapia , Estruturas Metalorgânicas/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Polietilenoglicóis/química , Porfirinas/farmacologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Oxigênio Singlete/metabolismo , Distribuição Tecidual , Microambiente Tumoral
15.
Biomacromolecules ; 19(6): 2043-2052, 2018 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-29584410

RESUMO

Biomimetic nanoengineering built through integrating the specific cell membrane with artificially synthetic nanomedicines represents one of the most promising directions for the actualization of personalized therapy. For addressing the technical hurdle against the development of this biomimetic technology, the present report describes the in-depth exploration and optimization over each critical preparation step, including establishment of a nanoparticle-stabilized dispersion system, cargo loading, membrane coating, and product isolation. Magnetic iron oxide nanoparticles loaded with DOX is used as a typical model for the coating with cancer cell membranes, providing compact DNP@CCCM nanostructure well-characterized by various techniques. Furthermore, the feasibility of this optimized approach in constructing biomimetic membrane-coated nanomedicines has been validated on the basis of the remarkably improved biofunctions, such as the targetability, magnetic property, hemolysis risk, macrophage evasion, in vitro cytotoxicity, in vivo circulation duration, and in vivo principal component analysis postinjection. We hope this study regarding technique optimization will prompt the advancement of biomembrane-camouflaged nanoparticles as a newly emerging biomimetic technology.


Assuntos
Antibióticos Antineoplásicos/farmacocinética , Membrana Celular/química , Nanopartículas de Magnetita/química , Nanomedicina/métodos , Animais , Antibióticos Antineoplásicos/administração & dosagem , Materiais Biomiméticos/química , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacocinética , Estabilidade de Medicamentos , Feminino , Células HeLa , Hemólise/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Camundongos Endogâmicos BALB C , Células RAW 264.7 , Coelhos , Ensaios Antitumorais Modelo de Xenoenxerto
16.
ACS Nano ; 12(4): 3917-3927, 2018 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-29578680

RESUMO

This study reports a family of photothermal materials, metal ion/tannic acid assemblies (MITAs). MITAs from FeIII, VIII, and RuIII afford excellent photothermal efficiency (η ≈ 40%). Sharply differing from the currently existing photothermal agents, MITAs are highlighted by merits including green synthesis, facile incorporation of diagnostic metal ions, and particularly topology-independent adhesion. Owing to the adhesion nature of MITAs, various kinds of MITA-based nanoengineerings are readily available via the self-adhesion of MITAs onto diverse templates, enabling MITAs well suited as a photothermal platform for versatile combination with other therapy approaches and imaging techniques. As a proof of concept, polymeric/inorganic nanoparticle/nanovesicle-supported FeIII-tannic acid (FeIIITA) is fabricated. The photothermal effect is shown to be unaffected by the template origin and type and FeIIITA thickness on the templates. We validate the potency of nanovesicle-supported FeIIITA (PNV@FeIIITA) for tumor-specific photoactivated utilizations, including NIR photothermal therapy with complete tumor elimination, photothermal imaging (PTI), and photoacoustic imaging (PAI) in addition to T1-MRI imaging. PNV@FeIIITA can be simultaneously equipped with functionalities, including T2-MRI imaging by additionally doping MnII and NIR fluorescence imaging by encapsulating a hydrophilic NIR fluoroprobe. MITA demonstrates unparalleled superiority as a photothermal platform in engineering multimodal theranostics for advanced applications.

17.
ACS Nano ; 12(2): 1978-1989, 2018 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-29420012

RESUMO

Metastasis and recurrence are two unavoidable and intractable problems in cancer therapy, despite various robust therapeutic approaches. Currently, it seems that immunotherapy is an effective approach to solve these problems, but the high heterogeneity of tumor tissue, inefficient presentation of tumor antigen, and deficient targeting ability of therapy usually blunt the efficacy of immunotherapy and hinder its clinical application. Herein, an approach based on combining photodynamic and immunological therapy was designed and developed. We synthesized a chimeric peptide, PpIX-1MT, which integrates photosensitizer PpIX with immune checkpoint inhibitor 1MT via a caspase-responsive peptide sequence, Asp-Glu-Val-Asp (DEVD), to realize a cascaded synergistic effect. The PpIX-1MT peptide could form nanoparticles in PBS and accumulate in tumor areas via the enhanced penetration retention effect. Upon 630 nm light irradiation, the PpIX-1MT nanoparticles produced reactive oxygen species, induced apoptosis of cancer cells, and thus facilitated the expression of caspase-3 and the production of tumor antigens, which could trigger an intense immune response. The subsequently released 1MT upon caspase-3 cleavage could further strengthen the immune system and help to activate CD8+ T cells effectively. This cascaded synergistic effect could inhibit both primary and lung metastasis tumor effectively, which may provide the solution for solving tumor recurrence and metastasis clinically.


Assuntos
Fatores Imunológicos/uso terapêutico , Imunoterapia/métodos , Neoplasias Pulmonares/terapia , Peptídeos/uso terapêutico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Protoporfirinas/uso terapêutico , Animais , Antígenos de Neoplasias/imunologia , Apoptose/efeitos dos fármacos , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Linhagem Celular Tumoral , Humanos , Fatores Imunológicos/química , Fatores Imunológicos/farmacocinética , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Camundongos , Nanopartículas/química , Nanopartículas/uso terapêutico , Peptídeos/química , Peptídeos/farmacocinética , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacocinética , Protoporfirinas/química , Protoporfirinas/farmacocinética
18.
Biomaterials ; 161: 81-94, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29421565

RESUMO

Nowadays, cell membrane targeting therapy has drawn much attention for its high anti-tumor effect by avoiding the cellular barriers. In this study, therapeutic agent conjugated chimeric peptide (Cp) was anchored in cracked cancer cell membranes (CCCM) to construct a self-delivery membrane system (M-Cp), which could relize precise cell membrane targeting therapy. It was found that compared with Cp, M-Cp could target to the cancer cell membrane with longer retention time, which is very crucial for in vivo applications. And the superior cell membrane targeting ability was attributed to the specific proteins (focal adhesion proteins, focal adhesion kinase, RHO family proteins, and integrin) on the CCCM surface. Importantly, the M-Cp could promote tumor-specific immune response, which further enhanced anti-tumor effect when combined with therapeutic agents in M-Cp. What's more, this self-delivery membrane system could be used as a template for cell membrane targeting therapy by changing the therapeutic agents as well as the CCCM, and this strategy would open a new window for various cell membrane targeting therapy.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Peptídeos/química , Animais , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Humanos , Modelos Biológicos
19.
Biomaterials ; 151: 1-12, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29040939

RESUMO

In this report, a biomimetic theranostic oxygen (O2)-meter (cancer cell membrane@Pt(II) porphyrinic-metal organic framework, designated as mPPt) was constructed for cancer targeted and phosphorescence image-guided photodynamic therapy (PDT). mPPt presents high photosensitizers (PSs) loading and evitable self-quenching behaviors for favorable biological O2 sensing and PDT. Besides, endowed by the surface functionalization of cancer cell membrane, the homotypic targeting and immune escape abilities of mPPt could dramatically enhance its cancer targeting ability. Importantly, the O2-dependent phosphorescence responsibility of mPPt could be employed to pre-evaluate the real time O2 level in situ and guide the PDT under light irradiation. A significant anticancer effect is observed after intravenous injection of mPPt and subsequent treatment with PDT with no obvious side effects. As a versatile platform for cell imaging, O2 fluctuation monitoring as well as PDT, this biomimetic O2-meter exhibits great potential for biological analysis and personalized cancer theranostics.


Assuntos
Antineoplásicos/química , Estruturas Metalorgânicas/química , Oxigênio/análise , Fotoquimioterapia/métodos , Nanomedicina Teranóstica/métodos , Animais , Antineoplásicos/farmacologia , Transporte Biológico , Biomimética/métodos , Linhagem Celular Tumoral , Complexos de Coordenação/química , Fluorescência , Haplorrinos , Humanos , Luz , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Imagem Óptica/métodos , Oxigênio/metabolismo , Tamanho da Partícula , Fármacos Fotossensibilizantes/química , Platina/química , Porfirinas/química , Propriedades de Superfície
20.
ACS Appl Mater Interfaces ; 9(49): 43143-43153, 2017 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-29168377

RESUMO

A universal strategy was reported that enables functional group-capped nanostructures with various morphologies and compositions to be coated by porphyrin metal-organic framework (MOF). Based on the nanostructure-induced heterogeneous nucleation, the controlled growth of MOF shell on the surface of nanostructures can be realized. It was demonstrated that this modification strategy can realize controlled growth of porphyrin MOF on a series of organic and inorganic nanostructures, such as polydopamine (PDA) nanoparticles, PDA@Pt nanoparticles, graphene oxide sheets, and Au nanorods. The as-prepared composites exhibit excellent catalytic and optical properties that originate from the nanostructure as well as the coated porphyrin MOF. We further explored the potential applications of PDA@MOF and PDA@Pt@MOF in nanomedicine and photocatalysis.

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