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Dinuclear iridium(III) complexes activated by light-inducible spatiotemporal control are emerging as promising candidates for cancer therapy. However, broader applications of current light-activated dinuclear iridium(III) complexes are limited by the ineffective tissue penetration and undesirable feedback on guidance activation. Here, an ultrasound (US) triggered near infrared-fluorescent dinuclear iridium(III) nanoparticle, NanoIr, is first reported to precisely and spatiotemporally inhibit tumor growth. It is demonstrated that reactive oxygen species can be generated by NanoIr upon exposure to US irradiation (NanoIr + US), thereby inducing immunogenic cell death. When combined with cisplatin, NanoIr + US elicits synergistic effects in patient-derived tumor xenograft mice models of ovarian cancer. This work first provides a design of dinuclear iridium(III) nanoparticles for immunogenic sonodynamic therapy.
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Cationic polymers have great potential for cancer therapy due to their unique interactions with cancer cells. However, their clinical application remains limited by their high toxicity. Here we show a cell membrane-targeting cationic polymer with antineoplastic activity (Pmt) and a second near-infrared (NIR-II) fluorescent biodegradable polymer with photosensitizer Bodipy units and reactive oxygen species (ROS) responsive thioketal bonds (PBodipy). Subsequently, these two polymers can self-assemble into antineoplastic nanoparticles (denoted mt-NPBodipy) which could further accumulate at the tumor and destroy cell membranes through electrostatic interactions, resulting in cell membrane destabilization. Meanwhile, the photosensitizer Bodipy produces ROS to induce damage to cell membranes, proteins, and DNAs to kill cancer cells concertedly, finally resulting in cell membrane lysis and cancer cell death. This work highlights the use of near-infrared light to spatially and temporarily control cationic polymers for photodynamic therapy, photo-immunotherapy, and NIR-II fluorescence for bio-imaging.
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Membrana Celular , Imunoterapia , Raios Infravermelhos , Nanopartículas , Fotoquimioterapia , Fármacos Fotossensibilizantes , Espécies Reativas de Oxigênio , Humanos , Nanopartículas/química , Membrana Celular/metabolismo , Membrana Celular/efeitos dos fármacos , Imunoterapia/métodos , Animais , Espécies Reativas de Oxigênio/metabolismo , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Camundongos , Fotoquimioterapia/métodos , Linhagem Celular Tumoral , Compostos de Boro/química , Compostos de Boro/farmacologia , Neoplasias/terapia , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Polímeros/química , Antineoplásicos/farmacologia , Antineoplásicos/química , FemininoRESUMO
Celastrol (CEL), an active compound isolated from the root of Tripterygium wilfordii, exhibits broad anticancer activities. However, its poor stability, narrow therapeutic window and numerous adverse effects limit its applications in vivo. In this study, an adenosine triphosphate (ATP) activatable CEL-Fe(III) chelate was designed, synthesized, and then encapsulated with a reactive oxygen species (ROS)-responsive polymer to obtain CEL-Fe nanoparticles (CEL-Fe NPs). In normal tissues, CEL-Fe NPs maintain structural stability and exhibit reduced systemic toxicity, while at the tumor site, an ATP-ROS-rich tumor microenvironment, drug release is triggered by ROS, and antitumor potency is restored by competitive binding of ATP. This intelligent CEL delivery system improves the biosafety and bioavailability of CEL for cancer therapy. Such a CEL-metal chelate strategy not only mitigates the challenges associated with CEL but also opens avenues for the generation of CEL derivatives, thereby expanding the therapeutic potential of CEL in clinical settings.
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Trifosfato de Adenosina , Triterpenos Pentacíclicos , Pró-Fármacos , Espécies Reativas de Oxigênio , Triterpenos Pentacíclicos/farmacologia , Triterpenos Pentacíclicos/química , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Trifosfato de Adenosina/metabolismo , Humanos , Animais , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Linhagem Celular Tumoral , Triterpenos/química , Triterpenos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Quelantes/química , Quelantes/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Microambiente Tumoral/efeitos dos fármacos , Liberação Controlada de Fármacos , Nanopartículas/química , Ensaios Antitumorais Modelo de Xenoenxerto , Compostos Férricos/químicaRESUMO
Over the last decades, a variety of metal complexes have been developed as chemotherapeutic agents. Despite the promising therapeutic prospects, the vast majority of these compounds suffer from low solubility, poor pharmacological properties, and most importantly poor tumor accumulation. To circumvent these limitations, herein, the incorporation of cytotoxic Ir(III) complexes and a variety of photosensitizers into polymeric gemini nanoparticles that selectively accumulate in the tumorous tissue and could be activated by near-infrared (NIR) light to exert an anticancer effect is reported. Upon exposure to light, the photosensitizer is able to generate singlet oxygen, triggering the rapid dissociation of the nanostructure and the activation of the Ir prodrug, thereby initiating a cascade of mitochondrial targeting and damage that ultimately leads to cell apoptosis. While selectively accumulating into tumorous tissue, the nanoparticles achieve almost complete eradication of the cisplatin-resistant cervical carcinoma tumor in vivo upon exposure to NIR irradiation.
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Antineoplásicos , Compostos de Boro , Raios Infravermelhos , Irídio , Nanopartículas , Polímeros , Nanopartículas/química , Humanos , Animais , Compostos de Boro/química , Compostos de Boro/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Irídio/química , Polímeros/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Feminino , Camundongos , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Fotoquimioterapia/métodos , Células HeLa , Camundongos NusRESUMO
Nanomaterials have attractive physicochemical properties. A variety of nanomaterials such as inorganic, lipid, polymers, and protein nanoparticles have been widely developed for nanomedicine via chemical conjugation or physical encapsulation of bioactive molecules. Superior to traditional drugs, nanomedicines offer high biocompatibility, good water solubility, long blood circulation times, and tumor-targeting properties. Capitalizing on this, several nanoformulations have already been clinically approved and many others are currently being studied in clinical trials. Despite their undoubtful success, the molecular mechanism of action of the vast majority of nanomedicines remains poorly understood. To tackle this limitation, herein, this review critically discusses the strategy of applying multiomics analysis to study the mechanism of action of nanomedicines, named nanomedomics, including advantages, applications, and future directions. A comprehensive understanding of the molecular mechanism could provide valuable insight and therefore foster the development and clinical translation of nanomedicines.
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Nanomedicina , Humanos , Animais , Nanoestruturas/química , GenômicaRESUMO
The integration of nanomedicine and immunotherapy has presented a promising opportunity for the treatment of cancer and diverse diseases. However, achieving spatiotemporal controllable immunotherapy with excellent efficacy and safety performances remains a significant challenge. This study develops a biodegradable near-infrared II (NIR-II) photothermal response polymer nanoparticle (PTEQ) system. This platform exhibits intrinsic immunostimulatory properties while concurrently delivering siRNA for Programmed Death-Ligand 1 (siPD-L1), leveraging enhanced immune responses and immune checkpoint blockade for safe and effective cancer therapy. In the CT26 tumor-bearing mouse model, PTEQ, as an immune stimulant, significantly boosts the infiltration of CD4+ and CD8+ T cells within the tumor microenvironment (TME). The PTEQ/siPD-L1+laser group not only initiates NIR-II photothermal therapy but also promotes the activation and infiltration of T cells, M1 macrophage polarization, and maturation of dendritic cells in the TME, resulting in the complete elimination of tumors in 7/10 cases, achieving a 100% survival rate. In another in vivo vaccine experiment, all tumors on the right side are completely eliminated in the PTEQ/siPD-L1+laser group, reaching a 100% tumor eradication rate. These findings underscore the potential of this strategy to overcome the current immunotherapeutic limitations and achieve immune therapy normalization.
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Imunoterapia , Raios Infravermelhos , Nanopartículas , Polímeros , Microambiente Tumoral , Animais , Camundongos , Nanopartículas/química , Microambiente Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral , Polímeros/química , Antígeno B7-H1/metabolismo , RNA Interferente Pequeno/química , Neoplasias/terapia , Neoplasias/imunologia , Terapia Fototérmica , Linfócitos T CD8-Positivos/imunologia , HumanosRESUMO
Recent years have witnessed substantial progress in cancer immunotherapy, specifically T cell-based therapies. However, the application of T cell therapies has been primarily limited to hematologic malignancies, with limited success in the treatment of solid tumors. The main challenge in treating solid tumor is immune escape, which is characterized by reduced antigenicity, diminished immunogenicity, and the development of suppressive tumor immune microenvironments. To address these obstacles and restore T cell-mediated anti-tumor responses, a novel nanoparticle formulation known as PRA@Oxa-c16 is developed. This innovative approach combines retinoic acid and Pt(IV) to specifically target and overcome immune escape. Notably, the therapeutic efficacy of PRA@Oxa-c16 primarily relies on its ability to induce anti-tumor T cell responses, in contrast to the cytotoxicity associated with conventional chemotherapeutic agents. When combined with an immune checkpoint blockade, anti-programmed death-ligand 1 antibody, PRA@Oxa-c16 effectively eliminates solid tumors and induces immune memory responses, which prevent tumor metastasis and recurrence. This promising approach holds great potential for enhancing the treatment of solid tumors with T cell-based immunotherapy.
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Antígeno B7-H1 , Linfócitos T CD8-Positivos , Imunoterapia , Nanomedicina , Pró-Fármacos , Pró-Fármacos/química , Pró-Fármacos/uso terapêutico , Pró-Fármacos/farmacologia , Imunoterapia/métodos , Linfócitos T CD8-Positivos/imunologia , Animais , Nanomedicina/métodos , Camundongos , Linhagem Celular Tumoral , Antígeno B7-H1/imunologia , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Nanopartículas/química , Neoplasias/terapia , Neoplasias/imunologia , Humanos , Platina/química , Tretinoína/química , Tretinoína/farmacologia , Tretinoína/uso terapêutico , Microambiente Tumoral/efeitos dos fármacos , Ativação Linfocitária/efeitos dos fármacos , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologiaRESUMO
The key dilemma for green hydrogen production via electrocatalytic water splitting is the high overpotential required for anodic oxygen evolution reaction (OER). Co/Fe-based materials show superior catalytic OER activity to noble metal-based catalysts, but still lag far behind the state-of-the-art Ni/Fe-based catalysts probably due to undesirable side segregation of FeOOH with poor conductivity and unsatisfied structural durability under large current density. Here, a robust and durable OER catalyst affording current densities of 500 and 1000 mA cm-2 at extremely low overpotentials of 290 and 304 mV in base is reported. This catalyst evolves from amorphous bimetallic FeOOH/Co(OH)2 heterostructure microsheet arrays fabricated by a facile mechanical stirring strategy. Especially, in situ X-ray photoelectron spectroscopy (XPS) and Raman analysis decipher the rapid reconstruction of FeOOH/Co(OH)2 into dynamically stable Co1-x Fex OOH active phase through in situ iron incorporation into CoOOH, which perform as the real active sites accelerating the rate-determining step supported by density functional theory calculations. By coupling with MoNi4 /MoO2 cathode, the self-assembled alkaline electrolyzer can deliver 500 mA cm-2 at a low cell voltage of 1.613 V, better than commercial IrO2 (+) ||Pt/C(-) and most of reported transition metal-based electrolyzers. This work provides a feasible strategy for the exploration and design of industrial water-splitting catalysts for large-scale green hydrogen production.
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Nitric oxide (NO) enhanced photodynamic therapy (PDT) is a promising approach to overcome drug tolerance and resistance to biofilm but is limited by its short excitation wavelengths and low yield of reactive oxygen species (ROS). Herein, we develop a compelling degradable polymer-based near-infrared II (NIR-II, 1000-1700 nm) photosensitizer (PNIR-II), which can maintain 50 % PDT efficacy even under a 2.6 cm tissue barrier. Remarkably, PNIR-II is synthesized by alternately connecting the electron donor thiophene to the electron acceptors diketopyrrolopyrrole (DPP) and boron dipyrromethene (BODIPY), where the intramolecular charge transfer properties can be tuned to increase the intersystem crossover rate and decrease the internal conversion rate, thereby stabilizing the NIR-II photodynamic rather than photothermal effect. For exerting a combination therapy to eradicate multidrug-resistant biofilms, PNIR-II is further assembled into nanoparticles (NPs) with a synthetic glutathione-triggered NO donor polymer. Under 1064 nm laser radiation, NPs precisely release ROS and NO that triggered by over-expressed GSH in the biofilm microenvironment, thereby forming more bactericidal reactive nitrogen species (RNS) in vitro and in vivo in the mice model that orderly destroy biofilm of multidrug-resistant Staphylococcus aureus cultures from clinical patients. It thus provides a new outlook for destroy the biofilm of deep tissues.
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Photodynamic therapy (PDT), as a new type of light-mediated reactive oxygen species (ROS) cancer therapy, has the advantages of high therapeutic efficiency, non-resistance, and less trauma than traditional cancer therapy such as surgery, radiotherapy, and chemotherapy. However, oxygen-dependent PDT further exacerbates tumor metastasis. To this end, a strategy that circumvents tumor metastasis to improve the therapeutic efficacy of PDT is proposed. Herein, a near-infrared light-activated photosensitive polymer is synthesized and branched the anti-metastatic ruthenium complex NAMI-A on the side, which is further assembled to form nanoparticles (NP2) for breast cancer therapy. NP2 can kill tumor cells by generating ROS under 808 nm radiation (NP2 + L), reduce the expression of matrix metalloproteinases (MMP2/9) in cancer cells, decrease the invasive and migration capacity of cancer cells, and eliminate cancer cells. Further animal experiments show that NP2 + L can inhibit tumor growth and reduce liver and lung metastases. In addition, NP2 + L can activate the immune system in mice to avoid tumor recurrence. In conclusion, a PDT capable of both preventing tumor metastasis and precisely hitting the primary tumor to achieve effective treatment of highly metastatic cancers is developed.
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Dimetil Sulfóxido/análogos & derivados , Nanopartículas , Compostos Organometálicos , Fotoquimioterapia , Compostos de Rutênio , Animais , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Recidiva Local de Neoplasia/tratamento farmacológico , Nanopartículas/uso terapêutico , Polímeros , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêuticoRESUMO
Photodynamic therapy (PDT) has been widely employed in tumor treatment due to its effectiveness. However, the tumor hypoxic microenvironment which is caused by abnormal vasculature severely limits the efficacy of PDT. Furthermore, the abnormal vasculature has been implicated in the failure of immunotherapy. In this study, a novel nanoparticle denoted as Combo-NP is introduced, composed of a biodegradable NIR II fluorescent pseudo-conjugate polymer featuring disulfide bonds within its main chain, designated as TPA-BD, and the vascular inhibitor Lenvatinib. Combo-NP exhibits dual functionality by not only inducing cytotoxic reactive oxygen species (ROS) to directly eliminate tumor cells but also eliciting immunogenic cell death (ICD). This ICD response, in turn, initiates a robust cascade of immune reactions, thereby augmenting the generation of cytotoxic T lymphocytes (CTLs). In addition, Combo-NP addresses the issue of tumor hypoxia by normalizing the tumor vasculature. This normalization process enhances the efficacy of PDT while concurrently fostering increased CTLs infiltration within the tumor microenvironment. These synergistic effects synergize to potentiate the photodynamic-immunotherapeutic properties of the nanoparticles. Furthermore, when combined with anti-programmed death-ligand 1 (PD-L1), they showcase notable inhibitory effects on tumor metastasis. The findings in this study introduce an innovative nanomedicine strategy aimed at triggering systemic anti-tumor immune responses for the treatment of Uveal melanoma.
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Nanopartículas , Fotoquimioterapia , Inibidores de Checkpoint Imunológico , Linhagem Celular Tumoral , Polímeros/química , Imunoterapia , Nanopartículas/químicaRESUMO
Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder that leads to cognitive impairment and memory loss. Emerging evidence suggests that autophagy plays an important role in the pathogenesis of AD through the regulation of amyloid-beta (Aß) and tau metabolism, and that autophagy dysfunction exacerbates amyloidosis and tau pathology. Therefore, targeting autophagy may be an effective approach for the treatment of AD. Animal models are considered useful tools for investigating the pathogenic mechanisms and therapeutic strategies of diseases. This review aims to summarize the pathological alterations in autophagy in representative AD animal models and to present recent studies on newly discovered autophagy-stimulating interventions in animal AD models. Finally, the opportunities, difficulties, and future directions of autophagy targeting in AD therapy are discussed.
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Doença de Alzheimer , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/veterinária , Peptídeos beta-Amiloides , Autofagia/fisiologia , Modelos AnimaisRESUMO
BACKGROUND: NK cells play an important role in immune response, immune surveillance, and metabolism regulation. Therefore, NK cells are involved in the occurrence and development of various diseases, such as infectious diseases, cancer, obesity, and diabetes. IL-25 is a special member of the IL-17 family with anti-inflammatory function. IL-25 can regulate inflammatory response and metabolism via various immune cells; however, the role and regulatory mechanism of IL-25 in NK cells are still unclear. METHOD: In this study, we investigate the role of IL-25 in NK-cell protein profile via 4D label-free mass spectrum and validate the differential proteins via PRM analysis. In addition, GO analysis, KEGG analysis, and other bioinformatic analysis methods are used to explore the enriched function and signal pathway of differentially expressed proteins. RESULT AND DISCUSSION: The GO and KEGG analyses suggest that IL-25 may affect the processes, such as metabolism, thermogenesis, and oxidative phosphorylation of NK cells. There are 7 down-regulated proteins (NCR1, GZMB, PRF1, KLRC1, NDUFA11, LAMTOR5, and IKBIP) and 1 up-regulated protein (PSMD7) in IL-25-treated NK cells versus the control group for PRM validation. Our results indicate that IL-25 may regulate metabolism and other biological processes via NK cells, which will be beneficial in revealing the role and regulatory mechanisms of IL-25 in NK cells in various diseases. CONCLUSION: Proteomics combined with bioinformatic analysis will help to mine more information hidden behind mass spectrometry data and lay the foundation for finding clinical biomarkers and mechanisms of diseases.
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Interleucina-17 , Proteômica , Interleucina-17/metabolismo , Células Matadoras Naturais/metabolismo , Espectrometria de Massas , Proteínas/metabolismo , Proteômica/métodos , HumanosRESUMO
Photodynamic therapy (PDT) and photothermal therapy (PTT) leverage reactive oxygen species (ROS) and control local hyperthermia by photosensitizer to perturb intracellular redox equilibrium, inducing DNA damage in both mitochondria and nucleus, activating the cGAS-STING pathway, ultimately eliciting antitumor immune responses. However, current photosensitizers are encumbered by limitations such as suboptimal tumor targeting, aggregation-caused quenching (ACQ), and restricted excitation and emission wavelengths. Here, this work designs novel nanoparticles based on aggregation-induced emission (AIE) photosensitizer (BODTPE) for targeted tumor therapy and near-infrared II fluorescence imaging (NIR-II FLI) with enhanced PDT/PTT effects. BODTPE is employed as a monomer, dibenzocyclooctyne (DBCO)-PEG2k -amine serving as an end-capping polymer, to synthesize a BODTPE-containing polymer (DBD). Further, through self-assembly, DBD and mPEG-DSPE2k combined to form nanoparticles (NP-DBD). Notably, the DBCO on the surface of NP-DBD can react with azide groups on cancer cells pretreated with Ac4 ManNAz through a copper-free click reaction. This innovative formulation led to targeted accumulation of NP-DBD within tumor sites, a phenomenon convincingly demonstrated in murine tumor models subjected to N-azidoacetylmannosamine-tetraacylated (Ac4 ManNAz) pretreatment. Significantly, NP-DBD exhibits a multifaceted effect encompassing PDT/PTT/NIR-II FLI upon 808 nm laser irradiation, thereby better activating the cGAS-STING pathway, culminating in a compelling tumor inhibition effect augmented by robust immune modulation.
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Nanopartículas , Neoplasias , Fotoquimioterapia , Animais , Camundongos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fotoquimioterapia/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Polímeros , Linhagem Celular TumoralRESUMO
Tumor metastases are considered the leading cause of cancer-associated deaths. While clinically applied drugs have demonstrated to efficiently remove the primary tumor, metastases remain poorly accessible. To overcome this limitation, herein, the development of a theranostic nanomaterial by incorporating a chromophore for imaging and a photosensitizer for treatment of metastatic tumor sites is presented. The mechanism of action reveals that the nanoparticles are able to intervene by local generation of cellular damage through photodynamic therapy as well as by systemic induction of an immune response by immunotherapy upon inhibition of the mTOR signaling pathway which is of crucial importance for tumor onset, progression and metastatic spreading. The nanomaterial is able to strongly reduce the volume of the primary tumor as well as eradicates tumor metastases in a metastatic breast cancer and a multi-drug resistant patient-derived hepatocellular carcinoma models in female mice.
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Neoplasias Hepáticas , Fotoquimioterapia , Feminino , Animais , Camundongos , Medicina de Precisão , Transdução de Sinais , Serina-Treonina Quinases TOR , ImunoterapiaRESUMO
Photodynamic therapy (PDT) has achieved great success in cancer treatment. Despite its great promise, the efficacy of photodynamic immunotherapy can be limited by the hypoxia in solid tumors which is closely related to the abnormal tumor vasculature. These abnormal vasculatures are a hallmark of most solid tumors and facilitate immune evasion. Therefore, tumor vascular normalization is developed as a promising strategy to overcome tumor hypoxia, resulting in improved cancer therapy. Here, a NIR-II bio-degradable pseudo-conjugate polymer (PSP)-based photodynamic polymer is designed to deliver a vascular normalization agent, i.e., regorafenib (Reg) in nanoparticles (NP-PDT@Reg). NP-PDT@Reg under 808 nm laser irradiation (NP-PDT@Reg + L) can efficiently release Reg to improve the tumor hypoxia via vascular normalization, making more NP-PDT@Reg and oxygen enter the tumors. Moreover, NP-PDT@Reg + L can further result in generation of more reactive oxygen species (ROS) to eradicate tumor cells while inducing immunogenic cell death (ICD) to activate anti-tumor immune responses. In addition, Reg can reprogram TAM from a pro-tumor M2 phenotype to a tumor-killing M1 phenotype as well, thereby reversing the immunosuppressive tumor microenvironment. Taken together, the current study provides an innovative perspective on the development of novel nanomaterials to overcome the limitations in photodynamic immunotherapy.
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Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fotoquimioterapia/métodos , Hipóxia Tumoral , Macrófagos Associados a Tumor , Linhagem Celular Tumoral , Neoplasias/tratamento farmacológico , Imunoterapia/métodos , Polímeros/farmacologia , Microambiente TumoralRESUMO
Rhinoplasty is a common surgical procedure in medical cosmetology. From patients with saddle nose deformity to beauty seekers with low and short noses, this surgery is mainly sought to improve the nose's appearance. To investigate the effect of modified auricular cartilage scaffold combined with L-shaped prosthesis in rhinoplasty. This retrospective study included 54 patients who underwent auricular cartilage augmentation rhinoplasty with L-shaped implants in our hospital from July 2018 to July 2021. The function of nasal ventilation and olfaction was inspected. As a result, the degree of nasal tip protrusion and the changes in the superior lip angle of columella were improved. The patients' satisfaction was measured a year after the surgery. Patients who underwent auricular cartilage augmentation rhinoplasty with L-shaped prosthesis were satisfied with the surgery outcomes. Using a protective auricular cartilage scaffold combined with an L-shaped implant for augmentation rhinoplasty reduced the shortage of the application and reinforced the stability of the auricular cartilage augmentation rhinoplasty. At >12 months follow-up, there were no serious adverse effects on nasal ventilation and olfactory function in any of the patients. The presented method made full use of auricular cartilage so that it reduced the harvest of the cartilage. Besides, it achieved the remarkable lift of the nose tip, thus simulating the appearance of costal cartilage rhinoplasty. Furthermore, the risk of implant exposure was efficiently reduced, making it worthy of clinical application.
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Cartilagem Costal , Implantes Dentários , Doenças Nasais , Rinoplastia , Humanos , Rinoplastia/métodos , Cartilagem da Orelha/cirurgia , Estudos Retrospectivos , Nariz/cirurgia , Septo Nasal/cirurgia , Cartilagem Costal/cirurgia , Doenças Nasais/cirurgiaRESUMO
Selective activation of Pt(IV) prodrugs within tumors is particularly attractive because of their low damage to normal tissues. However, current common activation via chemical/photoreduction of Pt(IV) prodrugs into Pt(II) counterparts is limited by undesirable spatial-temporal control over this reduction process and the ineffective tissue penetration depth of undesirable light. Here, a pseudo-conjugated-polymer is designed via Stille polymerization, resulting in PSP-Pt with a Pt(IV) prodrug of oxaliplatin (Oxa(IV)) in the polymer main chain that can be activated by NIR-II light. PSP-Pt can co-assemble with a commercially available lipid polymer, namely mPEG2k -DSPE, into NPPSP-Pt . Under 1064 nm light irradiation, NPPSP-Pt can be photoactivated to accelerate the Pt(IV) reduction to release oxaliplatin, thereby killing the cancer cells by photothermal effect and chemo-immunotherapy inside a mouse model with CT26 colon cancer. This work reports the application of NIR-II light for accelerating Pt(IV) reduction for cancer tumor therapy.
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Nanopartículas , Neoplasias , Pró-Fármacos , Camundongos , Animais , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico , Polímeros/uso terapêutico , Oxaliplatina , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Imunoterapia , Linhagem Celular TumoralRESUMO
The development of PtIV prodrugs that are reduced into the therapeutically active PtII species within the tumor microenvironment has received much research interest. In order to provide spatial and temporal control over the treatment, there is a high demand for the development of compounds that could be selectively activated upon irradiation. Despite recent progress, the majority of PtIV complexes are excited with ultraviolet or blue light, limiting the use of such compounds to superficial application. To overcome this limitation, herein, the first example of PtIV prodrug nanoparticles that could be reduced with deeply penetrating ultrasound radiation is reported, enabling the treatment of deep-seated or large tumors. The nanoparticles were found to selectively accumulate inside a mouse colon carcinoma tumor upon intravenous injection and were able to eradicate the tumor upon exposure to ultrasound radiation.
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Antineoplásicos , Nanopartículas , Neoplasias , Pró-Fármacos , Animais , Camundongos , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico , Platina/uso terapêutico , Neoplasias/tratamento farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
OBJECTIVE: The aim of this study was to analyze the epidemiological characteristics of pediatric facial soft tissue injuries of Chinese preschool-aged children in Hangzhou Plastic Surgery Hospital. METHODS: Medical records of preschool-aged children's facial injuries, 6 years and younger, from January 2017 to December 2019 were collected. Sex; age; time of injury; length of stay; causes of injury; location, type, length, and depth of wound; anesthesia methods; and treatment and evaluation of postoperative scars were analyzed. RESULTS: There were 10,862 cases (male, 6780 cases; female, 4082 cases) in the group. The ratio of male to female was 1.66:1. Mean age was 3.4 (±1.6) years; the youngest was 1 month old. The time of injury occurred frequently between 9:00 and 13:00 and 16:00 to 21:00, with the most common incident time being between 19:00 and 20:00. Collision injury was the main cause of injury (9822 [90.43%]). The most frequently injured area was the forehead (4874 [44.87%]). The main form of injury was laceration wound (9721 [89.45%]). The depth of injuries was mainly middle layer (adipose or muscular layer) (6299 [57.99%]). The length of injuries was 1.7 (±0.9) cm, ranging from 0.2 to 10.5 cm. Furthermore, 9110 cases were repaired by plastic surgeries and 1 or more antiscar measures. After 6-month to 2-year follow-up, 9 cases of animal scratch or bite, lip penetrating wound, or bumping teeth were infected and 26 cases had scar hyperplasia. The others achieved satisfactory results, and the scars were not obvious. CONCLUSION: Preschool-aged children's facial injuries have predictable patterns of occurrence, and targeted preventive measures can reduce the incidence rates. After facial injury, children should present for timely plastic surgery treatment and accept combined antiscarring measures to minimize postoperative scarring.