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1.
Adv Sci (Weinh) ; 11(6): e2306336, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38072677

RESUMEN

A critical challenge of existing cancer vaccines is to orchestrate the demands of antigen-enriched furnishment and optimal antigen-presentation functionality within antigen-presenting cells (APCs). Here, a complementary immunotherapeutic strategy is developed using dendritic cell (DC)-tumor hybrid cell-derived chimeric exosomes loaded with stimulator of interferon genes (STING) agonists (DT-Exo-STING) for maximized tumor-specific T-cell immunity. These chimeric carriers are furnished with broad-spectrum antigen complexes to elicit a robust T-cell-mediated inflammatory program through direct self-presentation and indirect DC-to-T immunostimulatory pathway. This chimeric exosome-assisted delivery strategy possesses the merits versus off-the-shelf cyclic dinucleotide (CDN) delivery techniques in both the brilliant tissue-homing capacity, even across the intractable blood-brain barrier (BBB), and the desired cytosolic entry for enhanced STING-activating signaling. The improved antigen-presentation performance with this nanovaccine-driven STING activation further enhances tumor-specific T-cell immunoresponse. Thus, DT-Exo-STING reverses immunosuppressive glioblastoma microenvironments to pro-inflammatory, tumoricidal states, leading to an almost obliteration of intracranial primary lesions. Significantly, an upscaling option that harnesses autologous tumor tissues for personalized DT-Exo-STING vaccines increases sensitivity to immune checkpoint blockade (ICB) therapy and exerts systemic immune memory against post-operative glioma recrudesce. These findings represent an emerging method for glioblastoma immunotherapy, warranting further exploratory development in the clinical realm.


Asunto(s)
Exosomas , Glioblastoma , Humanos , Glioblastoma/terapia , Linfocitos T , Presentación de Antígeno , Inmunoterapia/métodos , Microambiente Tumoral
2.
Acta Biomater ; 174: 386-399, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38016511

RESUMEN

Immune cells distinguish cancer cells mainly relying on their membrane-membrane communication. The major challenge of cancer vaccines exists in difficult identification of cancer neoantigens and poor understanding over immune recognition mechanisms against cancer cells, particularly the combination among multiple antigens and the cooperation between antigens and immune-associated proteins. We exploit cancer cell membranes as the whole cancer antigen repertoire and reinforce its immunogenicity by cellular engineering to modulate the cytomembrane's immune-associated functions. This study reports a vaccine platform based on radiation-engineered cancer cells, of which the membrane HSP70 protein as the immune chaperon/traitor is endogenously upregulated. The resulting positive influences are shown to cover immunogenic steps occurring in antigen-presenting cells, including the uptake and the cross-presentation of the cancer antigens, thus amplifying cancer-specific immunogenicity. Membrane vaccines offer chances to introduce desired metal ions through membrane-metal complexation. Using Mn2+ ion as the costimulatory interferon genes agonist, immune activity is enhanced to further boost adaptive cancer immunogenicity. Results have evidenced that this artificially engineered membrane vaccine with favorable bio-safety could considerably reduce tumorigenicity and inhibit tumor growth. This study provides a universally applicable and facilely available cancer vaccine platform by artificial engineering of cancer cells to inherit and amplify the natural merits of cancer cell membranes. STATEMENT OF SIGNIFICANCE: The major challenge of cancer vaccines exists in difficult identification of cancer neoantigens and poor understanding over immune recognition mechanisms against cancer cells, particularly the combination among multiple antigens and the cooperation between antigens and immune-associated proteins. Cancer cell membrane presents superior advantages as the whole cancer antigen repertoire, including the reported and the unidentified antigens, but its immunogenicity is far from satisfactory. Cellular engineering approaches offer chances to endogenously modulate the immune-associated functions of cell membranes. Such a reinforced vaccine based on the engineered cancer cell membranes matches better the natural immune recognition pathway than the conventional vaccines.


Asunto(s)
Vacunas contra el Cáncer , Neoplasias , Humanos , Neoplasias/prevención & control , Células Presentadoras de Antígenos , Antígenos de Neoplasias , Membrana Celular
3.
ACS Nano ; 17(13): 12471-12482, 2023 07 11.
Artículo en Inglés | MEDLINE | ID: mdl-37364286

RESUMEN

Calcium ion therapy is a potential anticancer treatment. However, the cellular calcium-buffering mechanism limited the effectiveness of calcium ion therapy. Here, we constructed a mineralized porphyrin metal-organic framework (PCa) to produce calcium ions and reactive oxygen species (ROS), which destroyed cell calcium buffering capacity and amplified the cell damage caused by calcium overload. In addition, PCa could induce cell immunogenic death to release tumor-associated antigen (TAA) and be used as an adjuvant. Thus, PCa could increase DC maturation and promote the antitumor activity of CD8+ T cells. For mice experiment, PCa not only showed excellent tumor elimination on the subcutaneous breast tumor but also achieved obvious antimetastasis effect in the metastatic tumor model. This nanosystem could eliminate the primary tumor and boost effective antitumor immunotherapy for comprehensive anticancer treatment.


Asunto(s)
Neoplasias Mamarias Animales , Estructuras Metalorgánicas , Neoplasias , Animales , Ratones , Estructuras Metalorgánicas/farmacología , Linfocitos T CD8-positivos , Calcio , Neoplasias/terapia , Inmunoterapia , Línea Celular Tumoral
4.
Nano Lett ; 23(4): 1219-1228, 2023 02 22.
Artículo en Inglés | MEDLINE | ID: mdl-36729055

RESUMEN

Due to the complexity and heterogeneity in the tumor microenvironment, the efficacy of breast cancer treatment has been significantly impeded. Here, we established a living system using an engineered M13 bacteriophage through chemical cross-linking and biomineralization to remodel the tumor microenvironment. Chemically cross-linking of the engineered bacteriophage gel (M13 Gel) could in situ synthesize photothermal palladium nanoparticles (PdNPs) on the pVIII capsid protein to obtain M13@Pd Gel. In addition, NLG919 was further loaded into a gel to form (M13@Pd/NLG gel) for down-regulating the expression of tryptophan metabolic enzyme indoleamine 2,3-dioxygenase 1 (IDO1). Both in vitro and in vivo studies showed that the M13 bacteriophage served not only as a cargo-loaded device but also as a self-immune adjuvant, which induced the immunogenic death of tumor cells effectively and down-regulated IDO1 expression. Such a bioactive gel system constructed by natural living materials could reverse immunosuppression and significantly improve the anti-breast cancer response.


Asunto(s)
Nanopartículas del Metal , Neoplasias , Microambiente Tumoral , Hidrogeles/uso terapéutico , Paladio , Bacteriófago M13
5.
Biomaterials ; 289: 121810, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36152517

RESUMEN

Radiotherapy is adopted to obliterate multiple malignant tumors clinically, which might also induce antitumor immune response. However, traditional radiotherapy is not enough to ablate tumors and activate long-term immunological response. Here, we developed a hybrid nanoplatform (MGTe) composed of GTe (glutathione (GSH) decorated Te nanoparticles) and fusing tumor cell membranes (TM) and bacterial outer membranes (BM). In this nanoplatform, GTe was designed for radiotherapy sensitization, concurrently the fusion of TM and BM was expected for amplifying antitumor immune. With a high-Z element, MGTe could enhance radiosensitivity by reactive oxygen species (ROS) production and cancer cell immunogenic death (ICD) under X-ray irradiation, which would also trigger antitumor immune. At meanwhile, TM and BM would further enlarge the immunological effects through antigen presenting cells (APCs) maturation and cytotoxic T lymphocytes (CTLs) stimulation. In this synergistic strategy, the combination of MGTe and X-ray showed significant tumor inhibition by radiation-driven immunotherapy, which will find great potential as an attractive clinical alternative to fight against tumor with reduced side effects.


Asunto(s)
Neoplasias de la Mama , Nanopartículas , Neoplasias , Biomimética , Neoplasias de la Mama/terapia , Línea Celular Tumoral , Femenino , Glutatión , Humanos , Inmunoterapia , Nanopartículas/uso terapéutico , Neoplasias/patología , Especies Reactivas de Oxígeno/metabolismo
6.
Biomaterials ; 289: 121763, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36055175

RESUMEN

Although cancer vaccines exhibit great advances in the field of immunotherapy, developing an efficient vaccine platform for personalized tumor immunotherapy is still a major challenge. Here we demonstrate that a bioactive vaccine platform (HMP@Ag) fabricated with hybrid M13 phage and personal tumor antigens can facilitate delivery of antigens into lymph nodes and activate antigen-presenting cells (APCs) through the Toll-like receptor 9 (TLR9) signaling pathway, which boosts both innate and adaptive immune response. As an adjuvant platform, hybrid M13 phages can deliver various tumor-specific antigens through simple adsorption to support the current development of personalized vaccines for cancers. Notably, the HMP@Ag vaccine not only prevented the tumors, but also delayed the tumor growth in established (subcutaneous and orthotopic) and metastatic tumor-bearing models while synergy with immune checkpoint blockade (ICB) therapy. Moreover, HMP@Ag triggered a robust neoantigen-based specific immune response in tumor-specific mutation models. In a clinically relevant surgery model, using autologous cell membrane from primary tumors-based HMP@Ag cooperation with ICB dramatically inhibited the post-operation recurrence, and elicited a long-term immune memory effect simultaneously. These findings imply that the M13 phage represents a powerful tool to develop a bio-activated hybrid platform for personalized therapy.


Asunto(s)
Vacunas contra el Cáncer , Neoplasias , Antígenos de Neoplasias , Bacteriófago M13 , Humanos , Inhibidores de Puntos de Control Inmunológico , Inmunoterapia , Neoplasias/terapia , Receptor Toll-Like 9
7.
ACS Nano ; 16(4): 5851-5866, 2022 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-35412799

RESUMEN

Conventional cancer targeting methodology needs to be reformed to overcome the intrinsic barriers responsible for poor targeting efficiency. This study describes a concept of self-reinforced cancer targeting (SRCT) by correlating targeting with therapy in a reciprocally enhancing manner. SRCT is achieved on the basis of two prerequisites: (1) target molecules have to be expressed on cancer cell membranes but not on normal cells, and (2) notably, their expression on cancer cells must be actively upregulated in response to cellular attack by cancer treatments. As a proof-of-concept, a GRP78-targeting nanovehicle for chemotherapy was designed. Resultant data showed that chemotherapeutic drugs could effectively elevate GRP78 expression on the plasma membranes of cancer cells while having minimal influence on normal cells. DOX pretreatment of cancer cells and tumor tissues can greatly increase the targeting efficacy and therapeutic performance of the prepared GRP78-targeting nanomedicine while somewhat disfavoring the nontargeting counterpart. In vivo and in vitro results demonstrated that this GRP78-targeting nanomedicine could accurately target cancer cells to not only implement chemotherapy but also induce GRP78 upregulation on cancer cells, eventually benefiting continuous cancer-cell-targeted attack by the nanomedicines remaining in the blood circulation or administered in the next dose. The GRP78-targeting nanomedicine displays much better antitumor performance compared with the nontargeting counterpart. SRCT is expected to advance cancer-targeted therapy based on the positive dependency between targeting and therapeutic modalities.


Asunto(s)
Antineoplásicos , Neoplasias , Humanos , Retroalimentación , Neoplasias/tratamiento farmacológico , Nanomedicina/métodos , Línea Celular Tumoral
8.
Nano Lett ; 22(6): 2217-2227, 2022 03 23.
Artículo en Inglés | MEDLINE | ID: mdl-35254071

RESUMEN

Agonists of stimulators of interferon genes (STING) are a promising class of immunotherapeutics that trigger potent innate immunity. However, the therapeutic efficacy of conventional STING agonists, such as 2',3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), is severely restricted to poor cytosolic delivery and lacks the capacity to promote the recognition of tumor-specific antigens. Here, we tackle these challenges through a nanovaccine platform based on Fenton-reactive and STING-activating nanoparticles, synergistically contributing to the generation of tumor-cell-derived apoptotic bodies (ABs). ABs loaded with exogenous cGAMP are readily phagocytosed by antigen-presenting cells (APCs), as a Trojan horse for rendering tumor cells with high immunogenicity instead of a noninflammatory response. This leads to enhanced STING activation and an improved tumor-specific antigen presentation ability, boosting the adaptive immunity in collaboration with innate immune. The strategy of exploiting a metal-based nanovaccine platform possesses great potential to be clinically translated into a trinitarian system of diagnosis, treatment, and prognosis.


Asunto(s)
Vesículas Extracelulares , Nanopartículas , Antígenos de Neoplasias , Inmunidad Innata , Inmunoterapia , Proteínas de la Membrana
9.
J Mater Chem B ; 10(10): 1634-1640, 2022 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-35194629

RESUMEN

Chemiluminescence substances that respond to hydrogen peroxide (H2O2) in a tumor microenvironment have the potential to achieve accurate tumor imaging. Here, Pluronic F-127 (PF127) and polymers containing oxalate ester (POE) were assembled by hydrophilic and hydrophobic forces to form nanoparticles to load the anti-tumor drug lapachone (Lapa) and rubrene. The Lapa-loaded H2O2-responsive nanoparticles (L-HPOX) could track tumors in vivo through H2O2-related chemiluminescence. With the presence of H2O2 in the tumor microenvironment, L-HPOX would collapse and release the loaded drug for anti-tumor therapy. After treatment with 5,6-dimethylxanthenone-4-acetic acid (DMXAA), the inflammatory level and H2O2 content increased. Thus, L-HPOX exhibited good capabilities of tumor imaging and treatment. Importantly, the immune system was also activated for anti-metastatic activity. This intelligent and efficient chemiluminescent tumor theranostic nanoplatform will find great potential for precise and efficient tumor treatment.


Asunto(s)
Peróxido de Hidrógeno , Neoplasias , Humanos , Peróxido de Hidrógeno/uso terapéutico , Luminiscencia , Neoplasias/tratamiento farmacológico , Medicina de Precisión , Microambiente Tumoral
10.
Natl Sci Rev ; 8(2): nwaa160, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34691571

RESUMEN

The hypoxic tumor microenvironment is characterized by disordered vasculature and rapid proliferation of tumors, resulting from tumor invasion, progression and metastasis. The hypoxic conditions restrict efficiency of tumor therapies, such as chemotherapy, radiotherapy, phototherapy and immunotherapy, leading to serious results of tumor recurrence and high mortality. Recently, research has concentrated on developing functional nanomaterials to treat hypoxic tumors. In this review, we categorize such nanomaterials into (i) nanomaterials that elevate oxygen levels in tumors for enhanced oxygen-dependent tumor therapy and (ii) nanomaterials with diminished oxygen dependence for hypoxic tumor therapy. To elevate oxygen levels in tumors, oxygen-carrying nanomaterials, oxygen-generating nanomaterials and oxygen-economizing nanomaterials can be used. To diminish oxygen dependence of nanomaterials for hypoxic tumor therapy, therapeutic gas-generating nanomaterials and radical-generating nanomaterials can be used. The biocompatibility and therapeutic efficacy of these nanomaterials are discussed.

11.
ACS Cent Sci ; 6(4): 555-565, 2020 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-32342005

RESUMEN

Photothermal therapy (PTT) is an effective treatment modality with high selectivity for tumor suppression. However, the inflammatory responses caused by PTT may lead to adverse reactions including tumor recurrence and therapeutic resistance, which are regarded as major problems for PTT. Here, a near-infrared (NIR) light-responsive nanoreactor (P@DW/BC) is fabricated to simultaneously realize tumor PTT and carbon monoxide (CO)-mediated anti-inflammatory therapy. Defective tungsten oxide (WO3) nanosheets (DW NSs) are decorated with bicarbonate (BC) via ferric ion-mediated coordination and then modified with polyethylene glycol (PEG) on the surface to fabricate PEG@DW/BC or P@DW/BC nanosheets. Upon 808 nm NIR laser irradiation, the DW content in P@DW/BC can serve as not only a photothermal agent to realize photothermal conversion but also a photocatalyst to convert carbon dioxide (CO2) to CO. In particular, the generated heat can also trigger the decomposition of BC to produce CO2 near the NSs, thus enhancing the photocatalytic CO generation. Benefiting from the efficient hyperthermia and CO generation under single NIR laser irradiation, P@DW/BC can realize effective thermal ablation of tumor and simultaneous inhibition of PTT-induced inflammation.

12.
iScience ; 23(1): 100778, 2020 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-31901818

RESUMEN

Natural enzymes are mainly composed by the protein part and metallic cofactor part, both of which work cooperatively to achieve high catalytic activity. Here, natural melanin particles (NMPs) were extracted from human hair and further bound with metal ions to mimic natural enzymes. The different metal-bound NMPs (M-NMPs) exhibited different enzyme-like activities with great promise in diverse biomedical applications. It was found that Fe-bound NMPs (Fe-NMPs) showed outstanding peroxidase (POD)-like activity that possessed potential in antibacterial applications, and Mn-bound NMPs (Mn-NMPs) displayed catalase (CAT)-like activity with a remarkable radiotherapy sensitization effect in cancer therapy. Besides, Cu-bound NMPs (Cu-NMPs) could serve as combined POD, superoxide dismutase (SOD), and CAT alternatives, which exhibited prominent reactive oxygen species (ROS) scavenging ability, revealing great potential in anti-inflammation. The versatile enzyme-like activities of M-NMPs derived from hair might give extensive perspective for designing biomedical materials and provide a promising tool in solving biomedical problems.

13.
Biomaterials ; 234: 119772, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31945618

RESUMEN

Photodynamic therapy (PDT) is a promising treatment modality for tumor suppression. However, the hypoxic state of most solid tumors might largely hinder the efficacy of PDT. Here, a functional covalent organic framework (COF) is fabricated to enhance PDT efficacy by remodeling the tumor extracellular matrix (ECM). Anti-fibrotic drug pirfenidone (PFD) is loaded in an imine-based COF (COFTTA-DHTA) and followed by the decoration of poly(lactic-co-glycolic-acid)-poly(ethylene glycol) (PLGA-PEG) to fabricate PFD@COFTTA-DHTA@PLGA-PEG, or PCPP. After injected intravenously, PCPP can accumulate and release PFD in tumor sites, leading to down-regulation of ECM compenents such as hyaluronic acid (HA) and collagen I. Such depletion of tumor ECM reduces the intratumoral solid stress, a compressive force exerted by the ECM and cells, decompresses tumor blood vessels, and increases the density of effective vascular areas, resulting in significantly improved oxygen supply in tumor. Furthermore, PCPP-mediated tumor ECM depletion also enhances the tumor uptake of subsequently injected Protoporphyrinl IX (PPIX)-conjugated peptide formed nanomicelles (NM-PPIX) due to the improved enhanced permeability and retention (EPR) effect. Both the alleviated tumor hypoxia and improved tumor homing of photosensitizer (PS) molecules after PCPP treatment significantly increase the reactive oxygen species (ROS) generation in tumor and therefore realize greatly enhanced PDT effect of tumor in vivo.


Asunto(s)
Estructuras Metalorgánicas , Nanopartículas , Neoplasias , Fotoquimioterapia , Línea Celular Tumoral , Matriz Extracelular , Humanos , Neoplasias/tratamiento farmacológico , Fármacos Fotosensibilizantes/uso terapéutico
14.
ACS Nano ; 13(12): 14230-14240, 2019 12 24.
Artículo en Inglés | MEDLINE | ID: mdl-31714733

RESUMEN

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.


Asunto(s)
Plaquetas/patología , Neoplasias/irrigación sanguínea , Neoplasias/terapia , Neovascularización Patológica/terapia , Hipoxia Tumoral , Células 3T3 , Animales , Aorta/patología , Biomimética , Adhesión Celular , Línea Celular Tumoral , Células Epiteliales/metabolismo , Femenino , Ratones , Ratones Endogámicos BALB C , Nanopartículas/química , Nanopartículas/ultraestructura
15.
Adv Sci (Weinh) ; 6(17): 1900835, 2019 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-31508286

RESUMEN

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.

16.
Nat Commun ; 10(1): 3199, 2019 07 19.
Artículo en Inglés | MEDLINE | ID: mdl-31324770

RESUMEN

Most cancer vaccines are unsuccessful in eliciting clinically relevant effects. Without using exogenous antigens and adoptive cells, we show a concept of utilizing biologically reprogrammed cytomembranes of the fused cells (FCs) derived from dendritic cells (DCs) and cancer cells as tumor vaccines. The fusion of immunologically interrelated two types of cells results in strong expression of the whole tumor antigen complexes and the immunological co-stimulatory molecules on cytomembranes (FMs), allowing the nanoparticle-supported FM (NP@FM) to function like antigen presenting cells (APCs) for T cell immunoactivation. Moreover, tumor-antigen bearing NP@FM can be bio-recognized by DCs to induce DC-mediated T cell immunoactivation. The combination of these two immunoactivation pathways offers powerful antitumor immunoresponse. Through mimicking both APCs and cancer cells, this cytomembrane vaccine strategy can develop various vaccines toward multiple tumor types and provide chances for accommodating diverse functions originating from the supporters.


Asunto(s)
Presentación de Antígeno/inmunología , Antígenos de Neoplasias/inmunología , Vacunas contra el Cáncer/inmunología , Membrana Celular/inmunología , Nanopartículas/uso terapéutico , Animales , Fusión Celular , Línea Celular Tumoral , Células Dendríticas/inmunología , Femenino , Inmunoterapia , Activación de Linfocitos , Neoplasias Mamarias Experimentales/inmunología , Neoplasias Mamarias Experimentales/prevención & control , Ratones , Ratones Endogámicos BALB C , Linfocitos T/inmunología , Transcriptoma , Trasplante Heterólogo
17.
ACS Nano ; 13(5): 5523-5532, 2019 05 28.
Artículo en Inglés | MEDLINE | ID: mdl-31046229

RESUMEN

Carbon monoxide (CO) is regarded as a potential therapeutic agent with multiple beneficial functions for biomedical applications. In this study, a versatile CO nanogenerator (designated as PPOSD) was fabricated and developed for tumor therapy and anti-inflammation. Partially oxidized tin disulfide (SnS2) nanosheets (POS NSs) were decorated with a tumor-targeting polymer (polyethylene glycol-cyclo(Asp-d-Phe-Lys-Arg-Gly), PEG-cRGD), followed by the loading of chemotherapeutic drug doxorubicin (DOX) to prepare polymer@POS@DOX, or PPOSD. After injected intravenously, PPOSD could selectively accumulate in tumor tissue via the cRGD-mediated tumor recognition. Upon 561 nm laser irradiation, the POS moiety in PPOSD can photoreduce CO2 to CO, which significantly sensitized the chemotherapeutic effect of DOX. The POS in PPOSD can also act as a photothermal agent for effective photothermal therapy (PTT) of the tumor upon 808 nm laser irradiation. Furthermore, the generated CO can simultaneously decrease the inflammatory reaction caused by PTT. Blood analysis and hematoxylin-eosin staining of major organs showed that no obvious systemic toxicity was induced after the treatment, suggesting good biosafety of PPOSD. This versatile CO nanogenerator will find great potential for both enhanced tumor inhibition and anti-inflammation.


Asunto(s)
Monóxido de Carbono/farmacología , Inflamación/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Dióxido de Carbono/química , Monóxido de Carbono/química , Línea Celular Tumoral , Disulfuros/química , Disulfuros/farmacología , Doxorrubicina/farmacología , Humanos , Inflamación/patología , Ratones , Nanopartículas/química , Neoplasias/patología , Ensayos Antitumor por Modelo de Xenoinjerto
18.
Adv Mater ; 31(18): e1900499, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30907473

RESUMEN

Using the cytomembranes (FMs) of hybrid cells acquired from the fusion of cancer and dendritic cells (DCs), this study offers a biologically derived platform for the combination of immunotherapy and traditional oncotherapy approaches. Due to the immunoactivation implicated in the cellular fusion, FMs can effectively express whole cancer antigens and immunological co-stimulatory molecules for robust immunotherapy. FMs share the tumor's self-targeting character with the parent cancer cells. In bilateral tumor-bearing mouse models, the FM-coated nanophotosensitizer causes durable immunoresponse to inhibit the rebound of primary tumors post-nanophotosensitizer-induced photodynamic therapy (PDT). The FM-induced immunotherapy displays ultrahigh antitumor effects even comparable to that of PDT. On the other hand, PDT toward primary tumors enhances the immunotherapy-caused regression of the irradiation-free distant tumors. Consequently, both the primary and the distant tumors are almost completely eliminated. This tumor-specific immunotherapy-based nanoplatform is potentially expandable to multiple tumor types and readily equipped with diverse functions owing to the flexible nanoparticle options.


Asunto(s)
Membrana Celular/química , Células Dendríticas/citología , Inmunoterapia , Nanoestructuras/química , Animales , Anticuerpos/química , Anticuerpos/inmunología , Línea Celular Tumoral , Células Dendríticas/metabolismo , Antígenos de Histocompatibilidad Clase II/inmunología , Receptores de Hialuranos/inmunología , Estructuras Metalorgánicas/química , Ratones , Ratones Desnudos , Nanoestructuras/uso terapéutico , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Fotoquimioterapia , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/uso terapéutico , Porfirinas/química , Porfirinas/uso terapéutico , Trasplante Heterólogo , Circonio/química
19.
Small ; 14(28): e1801120, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29882235

RESUMEN

Hypoxia is reported to participate in tumor progression, promote drug resistance, and immune escape within tumor microenvironment, and thus impair therapeutic effects including the chemotherapy and advanced immunotherapy. Here, a multifunctional biomimetic core-shell nanoplatform is reported for improving synergetic chemotherapy and immunotherapy. Based on the properties including good biodegradability and functionalities, the pH-sensitive zeolitic imidazolate framework 8 embedded with catalase and doxorubicin constructs the core and serves as an oxygen generator and drug reservoir. Murine melanoma cell membrane coating on the core provides tumor targeting ability and elicits an immune response due to abundance of antigens. It is demonstrated that this biomimetic core-shell nanoplatform with oxygen generation can be partial to accumulate in tumor and downregulate the expression of hypoxia-inducible factor 1α, which can further enhance the therapeutic effects of chemotherapy and reduce the expression of programmed death ligand 1 (PD-L1). Combined with immune checkpoints blockade therapy by programmed death 1 (PD-1) antibody, the dual inhibition of the PD-1/PD-L1 axis elicits significant immune response and presents a robust effect in lengthening tumor recurrent time and inhibiting tumor metastasis. Consequently, the multifunctional nanoplatform provides a potential strategy of synergetic chemotherapy and immunotherapy.


Asunto(s)
Antineoplásicos/farmacología , Antígeno B7-H1/metabolismo , Biomimética/métodos , Receptor de Muerte Celular Programada 1/metabolismo , Transducción de Señal , Hipoxia Tumoral/efectos de los fármacos , Animales , Linfocitos T CD8-positivos/metabolismo , Catalasa/metabolismo , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Citocinas/metabolismo , Doxorrubicina/farmacología , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Imidazoles/química , Ratones Endogámicos C57BL , Nanopartículas/química , Nanopartículas/ultraestructura , Neoplasias/inmunología , Neoplasias/patología , Oxígeno/farmacología , Zeolitas/química
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