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The immunosuppressive tumor microenvironment (TME) has become a major challenge in cancer immunotherapy, with abundant tumor-associated macrophages (TAMs) playing a key role in promoting tumor immune escape by displaying an immunosuppressive (M2) phenotype. Recently, it was reported that M1 macrophage-derived nanovesicles (M1NVs) can reprogram TAMs to an anti-tumor M1 phenotype, thereby significantly alleviating the immunosuppressive TME and enhancing the anti-tumor efficacy of immunotherapy. Herein, we developed M1NVs loaded with mesoporous dopamine (MPDA) and indocyanine green (ICG), which facilitated the recruitment of M2 TAMs through synergistic photothermal and photodynamic therapy. Thereafter, M1NVs can induce M1 repolarization of TAMs, resulting in increased infiltration of cytotoxic T lymphocytes within the tumor to promote tumor regression. This study investigated the effect of phototherapy on the immune environment of liver cancer using single-cell RNA sequencing (scRNA-seq) by comparing HCC tissues before and after MPDA/ICG@M1NVs + NIR treatment. The results showed significant shifts in cell composition and gene expression, with decreases in epithelial cells, B cells, and macrophages and increases in neutrophils and myeloid cells. Additionally, gene analysis indicated a reduction in pro-inflammatory signals and immunosuppressive functions, along with enhanced B-cell function and anti-tumor immunity, downregulation of the Gtsf1 gene in the epithelial cells of the MPDA/ICG @M1NVs + NIR group, and decreased expression of the lars2 gene in immune subpopulations. Eno3 expression is reduced in M1 macrophages, whereas Clec4a3 expression is downregulated in M2 macrophages. Notably, the B cell population decreased, whereas Pou2f2 expression increased. These genes regulate cell growth, death, metabolism, and tumor environment, indicating their key role in HCC progression. This study highlights the potential for understanding cellular and molecular dynamics to improve immunotherapy.
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Carbon monoxide (CO) has emerged as a potential antitumor agent by inducing the dysfunction of mitochondria and the apoptosis of cancer cells. However, it remains challenging to deliver appropriate amount of CO into tumor to ensure efficient tumor growth suppression with minimum side effects. Herein we developed a CO prodrug-loaded nanomedicine based on the self-assembly of camptothecin (CPT) polyprodrug amphiphiles. The polyprodrug nanoparticles readily dissociate upon exposure to endogenous H2O2 in the tumor, resulting in rapid release of CPT and generation of high-energy intermediate dioxetanedione. The latter can transfer the energy to neighboring CO prodrugs to activate CO production by chemiexcitation, while CPT promotes the generation of H2O2 in tumors, which in turn facilitates cascade CPT and CO release. As a result, the polyprodrug nanoparticles display remarkable tumor suppression in both subcutaneous and orthotopic breast tumor-bearing mice owing to the self-augmented CPT release and CO generation. In addition, no obvious systemic toxicity was observed in mice treated with the metal-free CO prodrug-loaded nanomedicine, suggesting the good biocompatibility of the polyprodrug nanoparticles. Our work provides new insights into the design and construction of polyprodrug nanomedicines for synergistic chemo/gas therapy.
Assuntos
Camptotecina , Monóxido de Carbono , Nanomedicina , Nanopartículas , Pró-Fármacos , Animais , Pró-Fármacos/farmacologia , Pró-Fármacos/química , Pró-Fármacos/uso terapêutico , Nanomedicina/métodos , Camptotecina/farmacologia , Camptotecina/uso terapêutico , Camptotecina/administração & dosagem , Camptotecina/química , Feminino , Humanos , Monóxido de Carbono/química , Nanopartículas/química , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Antineoplásicos/administração & dosagem , Peróxido de Hidrogênio/química , Camundongos NusRESUMO
Neuroinflammation has emerged as a major concern in ischemic stroke therapy because it exacebates neurological dysfunction and suppresses neurological recovery after ischemia/reperfusion. Fingolimod hydrochloride (FTY720) is an FDA-approved anti-inflammatory drug which exhibits potential neuroprotective effects in ischemic brain parenchyma. However, delivering a sufficient amount of FTY720 through the blood-brain barrier into brain lesions without inducing severe cardiovascular side effects remains challenging. Here, a neutrophil membrane-camouflaged polyprodrug nanomedicine that can migrate into ischemic brain tissues and in situ release FTY720 in response to elevated levels of reactive oxygen species. This nanomedicine delivers 15.2-fold more FTY720 into the ischemic brain and significantly reduces the risk of cardiotoxicity and infection compared with intravenously administered free drug. In addition, single-cell RNA-sequencing analysis identifies that the nanomedicine attenuates poststroke inflammation by reprogramming microglia toward anti-inflammatory phenotypes, which is realized via modulating Cebpb-regulated activation of NLRP3 inflammasomes and secretion of CXCL2 chemokine. This study offers new insights into the design and fabrication of polyprodrug nanomedicines for effective suppression of inflammation in ischemic stroke therapy.
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Cloridrato de Fingolimode , AVC Isquêmico , Nanomedicina , Neutrófilos , Animais , AVC Isquêmico/tratamento farmacológico , Camundongos , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Cloridrato de Fingolimode/química , Cloridrato de Fingolimode/farmacologia , Cloridrato de Fingolimode/uso terapêutico , Inflamação/tratamento farmacológico , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Membrana Celular/metabolismo , Membrana Celular/efeitos dos fármacos , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Microglia/efeitos dos fármacos , Microglia/metabolismo , Humanos , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêuticoRESUMO
Here, we proposed a novel solution for reversible regulation of the reactive oxygen species (ROS) level using a semiconductor heterojunction. Two metal-based ROS scavengers containing n-type CeO2 nanoparticles and n-type Cu-doped diatom biosilica (Cu-DBs) were integrated by a hydrothermal method to form a typical n-n semiconductor heterojunction (Ce/Cu-DBs). Unlike the control of the ROS level by a single ROS scavenger or ROS-generating agent, Ce/Cu-DBs could quickly eliminate ROS by cascade catalytic reaction, which readily switched to ROS generation through a near-infrared (NIR)-triggered photocatalytic effect. This NIR mediated ROS regulation system provided a noninvasive strategy for reversible control of the ROS level in vitro and in vivo. The Ce/Cu-DBs could relieve cellular oxidative stress by clearing local excessive ROS while inhibiting bacterial growth by increasing ROS levels under NIR radiation. Benefiting from the reversible regulatory effect of Ce/Cu-DBs, programmable healing of infected wounds was realized via on-demand anti-infection and inflammation reduction. This work provided a general method with highly spatiotemporal resolution to a remote and sustainable control ROS level, which had great potential for the biomedical field and regulation of chemical reactions.
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Nanopartículas , Espécies Reativas de Oxigênio , Catálise , Oxirredução , SemicondutoresRESUMO
Supramolecular polymers (SPs) have attracted broad interest because of their intriguing features and functions. Host-guest interactions often impart tunable physicochemical properties, reversible hierarchical organization, and stimuli-responsiveness to SPs for diverse biomedical applications. Characterized by strong but dynamic interactions with guest molecules, cucurbit[n]uril (CB[n]) has shown great potential as an important building block of various functional polymers for biomedical applications. In this Minireview, we summarize the most recent examples regarding the design, fabrication, and biomedical applications of CB[n]-based supramolecular polymers (CSPs), which are categorized as noncovalent and covalent CSPs according to the interactions between the CB[n] and polymer backbones. The design principles of CSPs and their unique advantages for biomedical applications, as well as the developmental trends and future perspectives of this cross-disciplinary area are also discussed.
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Compostos Macrocíclicos , Polímeros , Compostos Heterocíclicos com 2 Anéis , Imidazolidinas , Polímeros/químicaRESUMO
Bacterial infection has become a global concern owing to the significant morbidity and mortality. Although the phagocytosis of bacteria by immune cells acts as the front line to protect human body from invading pathogens, the relatively slow encounter and insufficient capture of bacteria by immune cells often lead to an inefficient clearance of pathogens. Herein, a supramolecular artificial receptor-modified macrophage (SAR-Macrophage) was developed to enhance the recognition and latch of bacteria in the systemic circulation, mediated via strong and multipoint host-guest interactions between the artificial receptors (cucurbit[7]uril) on the macrophage and the guest ligands (adamantane) selectively anchored on Escherichia coli (E. coli). As a result, the SAR-Macrophage could significantly accelerate the recognition of E. coli, catch and internalize more pathogens, which subsequently induced the M1 polarization of macrophages to generate ROS and effectively kill the intracellular bacteria. Therefore, the SAR-Macrophage represents a simple, yet powerful anti-bacterial approach.
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Escherichia coli , Interações entre Hospedeiro e Microrganismos/imunologia , Macrófagos , Receptores Artificiais , Escherichia coli/imunologia , Macrófagos/imunologia , Macrófagos/microbiologia , FagocitoseRESUMO
Bioorthogonal chemistry is a powerful tool to site-specifically activate drugs in living systems. Bioorthogonal reactions between a pair of biologically reactive groups can rapidly and specifically take place in a mild physiological milieu without perturbing inherent biochemical processes. Attributed to their high selectivity and efficiency, bioorthogonal reactions can significantly decrease background signals in bioimaging. Compared with metal-catalyzed bioorthogonal click reactions, metal-free click reactions are more biocompatible without the metal catalyst-induced cytotoxicity. Although a great number of bioorthogonal chemistry-based strategies have been reported for cancer theranostics, a comprehensive review is scarce to highlight the advantages of these strategies. In this review, recent progress in cancer theranostics guided by metal-free bioorthogonal click chemistry will be depicted in detail. The elaborate design as well as the advantages of bioorthogonal chemistry in tumor theranostics are summarized and future prospects in this emerging field are emphasized.
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Química Click , Neoplasias , Catálise , Humanos , Metais , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Medicina de PrecisãoRESUMO
Nanomedicines have the potential to provide advanced therapeutic strategies in combating tumors. Polymer-prodrug-based nanomedicines are particularly attractive in cancer therapies owing to the maximum drug loading, prolonged blood circulation, and reduced premature leakage and side effects in comparison with conventional nanomaterials. However, the difficulty in precisely tuning the composition and drug loading of polymer-drug conjugates leads to batch-to-batch variations of the prodrugs, thus significantly restricting their clinical translation. Polyprodrug nanomedicines inherit the numerous intrinsic advantages of polymer-drug conjugates and exhibit well-controlled composition and drug loading via direct polymerization of therapeutic monomers, representing a promising nanomedicine for clinical tumor therapies. In this review, recent advances in the development of polyprodrug nanomedicines are summarized for tumor elimination. Various types of polyprodrug nanomedicines and the corresponding properties are first summarized. The unique advantages of polyprodrug nanomedicines and their key roles in various tumor therapies are further highlighted. Finally, current challenges and the perspectives on future research of polyprodrug nanomedicines are discussed.
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Antineoplásicos , Neoplasias , Pró-Fármacos , Antineoplásicos/uso terapêutico , Sistemas de Liberação de Medicamentos , Humanos , Nanomedicina , Neoplasias/tratamento farmacológico , Polímeros/uso terapêutico , Pró-Fármacos/uso terapêuticoRESUMO
Gas therapy has emerged as a new therapeutic strategy in combating cancer owing to its high therapeutic efficacy and biosafety. However, the clinical translation of gas therapy remains challenging due to the rapid diffusion and limited tissue penetration of therapeutic gases. Herein, a self-propelled, asymmetrical Au@MnO2 nanomotor for efficient delivery of therapeutic gas to deep-seated cancer tissue for enhanced efficacy of gas therapy, is reported. The Au@MnO2 nanoparticles (NPs) catalyze endogenous H2 O2 into O2 that propels NPs into deep solid tumors, where SO2 prodrug is released from the hollow NPs owing to the degradation of MnO2 shells. Fluorescein isothiocyanate (FITC) is conjugated onto the surface of Au via caspase-3 responsive peptide (DEVD) and the therapeutic process of gas therapy can be optically self-reported by the fluorescence of FITC that is turned on in the presence of overexpressed caspase-3 as an apoptosis indicator. Au@MnO2 nanomotors show self-reported therapeutic efficacy and high biocompatibility both in vitro and in vivo, offering important new insights to the design and development of novel nanomotors for efficient payload delivery into deep tumor tissue and in situ monitoring of the therapeutic process.
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Compostos de Manganês , Nanopartículas , Gases , Humanos , Óxidos , AutorrelatoRESUMO
The precise accumulation and extended retention of nanomedicines in the tumor tissue has been highly desired for cancer therapy. Here a novel supramolecular-peptide derived nanodrug (SPN) that can be transformed to microfibers in response to intracellular polyamine in cancer cells for significantly enhanced tumor specific accumulation and retention is developed. The supramolecular-peptide is constructed via the non-covalent interactions between cucurbit[7]uril (CB[7]) and Phe on Phe-Phe-Val-Leu-Lys-camptothecin conjugates (FFVLK-CPT, PC). The resultant amphiphilic supramolecular complex subsequently self-assembles into nanoparticles with a hydrodynamic diameter of 164.2 ± 3.7 nm. Upon internalization into spermine-overexpressed cancer cells, the CB[7]-Phe host-guest pairs can be competitively dissociated by spermine and can release free PC, which immediately form ß-sheet structures and subsequently reorganize into microfibers, leading to dramatically improved accumulation, retention, and sustained release of CPT in tumor cells for highly effective cancer therapy. Accordingly, this SPN exhibit rather low toxicity against non-cancerous cells due to the morphological stability and fast exocytosis of the nanodrugs in those cells without abundant spermine. This study reports the first supramolecular peptide capable of polyamine-responsive "nanoparticle-to-microfiber" transformation for specific tumor therapy with minimal side effects. This work also offers novel insights to the design and development of stimuli-responsive nanomaterials as precision medicine.
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Neoplasias , Preparações Farmacêuticas , Humanos , Nanomedicina , Neoplasias/tratamento farmacológico , Peptídeos , PoliaminasRESUMO
The hypoxic tumor microenvironment (TME) and non-specific distribution of sonosensitizers are two major obstacles that limit practical applications of sonodynamic therapy (SDT) in combating tumors. Here we report a hypoxia-responsive nanovesicle (hMVs) as delivery vehicles of a sonosensitizer to enhance the efficacy of SDT via specific payload release and local oxygenation in the tumor. The nanovesicles are composed of densely packed manganese ferrite nanoparticles (MFNs) embedded in hypoxia-responsive amphiphilic polymer membranes. With δ-aminolevulinic acid (ALA) loaded in the hollow cavities, the hMVs could rapidly dissociate into discrete nanoparticles in the hypoxic TME to release the payload and induce the generation of reactive oxygen species (ROS) under ultrasound (US) radiation. Meanwhile, the released MFNs could catalytically generate O2 to overcome the hypoxic TME and thus enhance the efficacy of SDT. After treatment, the dissociated MFNs could be readily excreted from the body via renal clearance to reduce long term toxicity. In vitro and in vivo experiments displayed effective tumor inhibition via hMVs-mediated SDT, indicating the great potential of this unique nanoplatform in effective SDT by generating sufficient ROS in deep-seated hypoxic tumors that are not readily accessible by conventional photodynamic therapy.
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Hipóxia , Nanopartículas , Linhagem Celular Tumoral , Humanos , Espécies Reativas de Oxigênio , Microambiente TumoralRESUMO
The clinical application of chemodynamic therapy is impeded by the insufficient intracellular H2 O2 level in tumor tissues. Herein, we developed a supramolecular nanoparticle via a simple one-step supramolecular polymerization-induced self-assembly process using platinum (IV) complex-modified ß-cyclodextrin-ferrocene conjugates as supramolecular monomers. The supramolecular nanoparticles could dissociate rapidly upon exposure to endogenous H2 O2 in the tumor and release hydroxyl radicals as well as platinum (IV) prodrugs in situ, which is reduced into cisplatin to significantly promote the generation of H2 O2 in the tumor tissue. Thus, the supramolecular nanomedicine overcomes the limitation of conventional chemodynamic therapy via the self-augmented cascade radical generation and drug release. In addition, dissociated supramolecular nanoparticles could be readily excreted from the body via renal clearance to effectively avoid systemic toxicity and ensure long term biocompatibility of the nanomedicine. This work may provide new insights on the design and development of novel supramolecular nanoassemblies for cascade chemo/chemodynamic therapy.
Assuntos
Antineoplásicos/uso terapêutico , Portadores de Fármacos/uso terapêutico , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Polímeros/uso terapêutico , Animais , Antineoplásicos/síntese química , Antineoplásicos/metabolismo , Antineoplásicos/toxicidade , Linhagem Celular Tumoral , Complexos de Coordenação/síntese química , Complexos de Coordenação/metabolismo , Complexos de Coordenação/uso terapêutico , Complexos de Coordenação/toxicidade , Portadores de Fármacos/síntese química , Portadores de Fármacos/metabolismo , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Feminino , Compostos Ferrosos/síntese química , Compostos Ferrosos/metabolismo , Compostos Ferrosos/uso terapêutico , Compostos Ferrosos/toxicidade , Peróxido de Hidrogênio/metabolismo , Radical Hidroxila/metabolismo , Metalocenos/síntese química , Metalocenos/metabolismo , Metalocenos/uso terapêutico , Metalocenos/toxicidade , Camundongos Endogâmicos BALB C , Nanomedicina/métodos , Nanopartículas/química , Nanopartículas/metabolismo , Nanopartículas/toxicidade , Platina/química , Polimerização , Polímeros/síntese química , Polímeros/metabolismo , Polímeros/toxicidade , Pró-Fármacos/química , Pró-Fármacos/metabolismo , Pró-Fármacos/uso terapêutico , Pró-Fármacos/toxicidade , beta-Ciclodextrinas/síntese química , beta-Ciclodextrinas/metabolismo , beta-Ciclodextrinas/uso terapêutico , beta-Ciclodextrinas/toxicidadeRESUMO
Glucose starvation has emerged as a therapeutic strategy to inhibit tumor growth by regulating glucose metabolism. However, the rapid proliferation of cancer cells could induce the hypoxic tumor microenvironment (TME) which limits the therapeutic efficacy of glucose starvation by vascular isomerization. Herein, we developed a "dual-lock" supramolecular nanomedicine system for synergistic cancer therapy by integrating glucose oxidase (GOx) induced starvation and hypoxia-activated gene therapy. The host-guest interactions (that mediate nano-assembly formation) and hypoxia-activatable promoters act as two locks to keep glucose oxidase (GOx) and a therapeutic plasmid (RTP801::p53) inside supramolecular gold nanovesicles (Au NVs). Upon initial dissociation of the host-guest interactions and hence Au NVs by cancer-specific reactive oxygen species (ROS), GOx is released to consume glucose and oxygen, generate H2O2 and induce the hypoxic TME, which act as the two keys for triggering burst payload release and promoter activation, thus allowing synergistic starvation and gene therapy of cancer. This "dual-lock" supramolecular nanomedicine exhibited integrated therapeutic effects in vitro and in vivo for tumor suppression.
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Glucose , Neoplasias , Terapia Genética , Glucose Oxidase , Humanos , Peróxido de Hidrogênio , Hipóxia , Neoplasias/terapia , Microambiente TumoralRESUMO
Effectively activating macrophages against cancer is promising but challenging. In particular, cancer cells express CD47, a 'don't eat me' signal that interacts with signal regulatory protein alpha (SIRPα) on macrophages to prevent phagocytosis. Also, cancer cells secrete stimulating factors, which polarize tumor-associated macrophages from an antitumor M1 phenotype to a tumorigenic M2 phenotype. Here, we report that hybrid cell membrane nanovesicles (known as hNVs) displaying SIRPα variants with significantly increased affinity to CD47 and containing M2-to-M1 repolarization signals can disable both mechanisms. The hNVs block CD47-SIRPα signaling axis while promoting M2-to-M1 repolarization within tumor microenvironment, significantly preventing both local recurrence and distant metastasis in malignant melanoma models. Furthermore, by loading a stimulator of interferon genes (STING) agonist, hNVs lead to potent tumor inhibition in a poorly immunogenic triple negative breast cancer model. hNVs are safe, stable, drug loadable, and suitable for genetic editing. These properties, combined with the capabilities inherited from source cells, make hNVs an attractive immunotherapy.
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Micropartículas Derivadas de Células/imunologia , Imunoterapia/métodos , Macrófagos/imunologia , Melanoma/terapia , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias de Mama Triplo Negativas/terapia , Animais , Antígeno CD47/metabolismo , Linhagem Celular Tumoral/transplante , Modelos Animais de Doenças , Feminino , Células HEK293 , Humanos , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Melanoma/imunologia , Melanoma/secundário , Proteínas de Membrana/agonistas , Proteínas de Membrana/imunologia , Camundongos , Nanopartículas/administração & dosagem , Recidiva Local de Neoplasia/imunologia , Nucleotídeos Cíclicos/administração & dosagem , Receptores Imunológicos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Neoplasias de Mama Triplo Negativas/imunologia , Evasão Tumoral/efeitos dos fármacos , Evasão Tumoral/imunologia , Microambiente Tumoral/imunologiaRESUMO
The effort of incorporating therapeutic drugs with imaging agents has been one of the mainstreams of nanomedicine, which holds great promise in cancer treatment in terms of monitoring therapeutic drug activity and evaluating prognostic index. However, it is still technically challenging to develop nanomedicine endowing a spatiotemporally controllable mechanism of drug release and activatable imaging capability. Here, we developed a yolk-shell type of GSH-responsive nanovesicles (NVs) in which therapeutic drug (Doxorubicin, DOX) and magnetic resonance imaging (MRI) contrast agent (ultrasmall paramagnetic iron oxide nanoparticles, USPIO NPs) formed complexes (denoted as USD) and were encapsulated inside the NVs. The formation of USD complexes is mediated by both the electrostatic adsorption between DOX and poly(acrylic acid) (PAA) polymers and the DOX-iron coordination effect on USPIO NPs. The obtained USD NVs showed a unique yolk-shell structure with restrained drug activity and quenched T1 MRI contrast ability which, on the other hand, can respond to glutathione (GSH) and lead to drug release and T1 contrast activation in a spatiotemporally concurrent manner. Furthermore, the USD NVs exhibited great potential to kill HCT116 cancer cells in vitro and effectively inhibit the tumor growth in vivo. This study may shed light on the design of sophisticated nanotheranostics in precision nanomedicine.
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Nanopartículas , Neoplasias , Doxorrubicina , Liberação Controlada de Fármacos , Glutationa , Humanos , Imageamento por Ressonância Magnética , Medicina de Precisão , Nanomedicina TeranósticaRESUMO
This article describes the fabrication of hollow manganese/cobalt oxide nanoparticles (MCO NPs) with a tunable size through a redox reaction and the Kirkendall effect for cancer imaging and drug delivery. MCO-70 NPs (with an average size of 70 nm) can act as glutathione (GSH)-responsive contrast agents for dual T1/T2-weighted magnetic resonance imaging (MRI). The degradation of MCO NPs by GSH led to the enhancement of their T1 and T2 signals by 2.24- and 3.43-fold compared with those of MCO NPs before degradation, respectively. Antitumor agents such as doxorubicin (Dox) could be encapsulated inside the cavity of the hollow MCO NPs (MCO-70-Dox) and be released in the presence of GSH. The MCO-70-Dox NPs showed good tumor growth inhibition effects in vitro and in vivo, and can be promising drug delivery vehicles and MRI contrast agents for tumor diagnosis and reporting drug release.
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Cobalto/química , Compostos de Manganês/química , Nanopartículas Metálicas/química , Óxidos/química , Nanomedicina Teranóstica/métodos , Implantes Absorvíveis , Animais , Antineoplásicos/farmacologia , Meios de Contraste , Doxorrubicina/farmacologia , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Glutationa/química , Humanos , Íons , Imageamento por Ressonância Magnética , Camundongos , Camundongos Nus , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Transplante de Neoplasias , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Oxirredução , Eletricidade Estática , Tensoativos , Raios XRESUMO
Hydrogels with shapes that can be adapted to their environment have attracted great attention from both academia and industry. We report herein a new and robust strategy to reprogram the light-induced shape transformation of a thermoresponsive composite hydrogel sheet with erasable and rewritable patterns of iron oxide nanoparticles as photothermal agents. Numerous distinct and reversible shape transformations are achieved from a single hydrogel sheet by repeatably writing in the sheet with different nanoparticle patterns. The shape transformations were verified by finite element modeling. The present strategy is simple, fast, and efficient in reprogramming the shape change of the thermoresponsive hydrogel material. The composite hydrogel sheet may find applications in soft robotics, tissue engineering, and controlled release.
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This article describes a nanoplatform based on matrix metalloproteinase (MMP)-responsive gold nanoparticles (AuNPs) for tumor-targeted photoacoustic (PA) imaging-guided photothermal therapy and drug delivery. AuNPs were grafted with complementary DNA strands, tethered with doxorubicin and coated with poly(ethylene glycol) via a thermal-labile linker and a MMP-cleavable peptide, respectively. The nanoprobes remained well-isolated in healthy tissues, but formed aggregates rapidly under MMP-abundant conditions. The DNA hybridization-induced assembly of the nanoprobes led to prolonged tumor retention and strong near-infrared (NIR) absorption, which is beneficial to deep-tissue imaging and therapy. Compared with MMP-inert nanoprobes, our platform demonstrated significantly enhanced efficiency in PA imaging and photothermal conversion upon NIR irradiation. Meanwhile, doxorubicin could be released rapidly in response to the localized elevation of temperature, leading to synergistic chemo-photothermal therapy. The unique nanoplatform may find applications in effective disease control by delivering imaging and therapy to tumors with high specificity, safety, and universality.