A multifunctional biomimetic nanoplatform for image-guideded photothermal-ferroptotic synergistic osteosarcoma therapy⋆
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ABSTRACT:
SUBMITTER: Liu Y
PROVIDER: S-EPMC10924166 | biostudies-literature | 2024 Mar
REPOSITORIES: biostudies-literature
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Project description:BackgroundPhotothermal therapy (PTT) is taken as a promising strategy for cancer therapy, however, its applicability is hampered by cellular thermoresistance of heat shock response and insufficient accumulation of photothermal transduction agents in the tumor region. In consideration of those limitations, a multifunctional "Golden Cicada" nanoplatform (MGCN) with efficient gene delivery ability and excellent photothermal effects is constructed, overcoming the thermoresistance of tumor cells and improving the accumulation of indocyanine green (ICG).ResultsDown-regulation of heat shock protein 70 (HSP70) makes tumor cells more susceptible to PTT, and a better therapeutic effect is achieved through such cascade augmented synergistic effects. MGCN has attractive features with prolonged circulation in blood, dual-targeting capability of CD44 and sialic acid (SA) receptors, and agile responsiveness of enzyme achieving size and charge double-variable transformation. It proves that, on the one hand, MGCN performs excellent capability for HSP70-shRNA delivery, resulting in breaking the cellular thermoresistance mechanism, on the other hand, ICG enriches in tumor site specifically and possesses a great thermal property to promoted PTT.ConclusionsIn short, MGCN breaks the protective mechanism of cellular heat stress response by downregulating the expression of HSP70 proteins and significantly augments synergistic effects of photothermal/gene therapy via cascade augmented synergistic effects.
| S-EPMC10353101 | biostudies-literature
Project description:Phototherapy, including photothermal therapy (PTT) and photodynamic therapy (PDT), has been considered as a noninvasive option for cancer therapy. However, insufficient penetration depth, tumor hypoxia, and a single treatment method severely limit the effectiveness of treatment. Methods: In this study, a multifunctional theranostic nanoplatform has been fabricated based on Au/Ag-MnO2 hollow nanospheres (AAM HNSs). The Au/Ag alloy HNSs were first synthesized by galvanic replacement reaction and then the MnO2 nanoparticles were deposited on the Au/Ag alloy HNSs by the reaction between Ag and permanganate (KMnO4), finally obtained the AAM HNSs. Then, SH-PEG was modified on the surface of AAM HNSs by the interaction of sulfhydryl and Au/Ag alloy, which improved the dispersibility and biocompatibility of the HNS. Next, the PDT photosensitizer Ce6 was loaded into AAM HNSs, benefiting from the hollow interior of the structure, and the AAM-Ce6 HNSs were obtained. Results: The AAM HNSs exhibit broad absorption at the near infrared (NIR) biological window and remarkable photothermal conversion ability in the NIR-II window. The MnO2 nanoparticles can catalyze endogenous H2O2 to generate O2 and enhance the therapeutic effect of PDT on tumor tissue. Simultaneously, MnO2 nanoparticles intelligently respond to the tumor microenvironment and degrade to release massive Mn2+ ions, which introduce magnetic resonance imaging (MRI) properties. When AAM-Ce6 HNSs are loaded with Ce6, the AAM-Ce6 HNSs can be used for triple-modal imaging (fluorescence/photoacoustic/magnetic resonance imaging, FL/PAI/MRI) guided combination tumor phototherapy (PTT/PDT). Conclusion: This multifunctional nanoplatform shows synergistic therapeutic efficacy better than any single therapy by achieving multimodal imaging guided cancer combination phototherapy, which are promising for the diagnosis and treatment of cancer.
| S-EPMC6831477 | biostudies-literature
Project description:In summary, highly stability and dispersed BSArGO@ZIF8 NSs were prepared by a simple electrostatic interaction method. According to the delivery effect of BSArGO@ZIF8 NSs, we found that BSArGO@ZIF8 NSs possess higher lethality to cancer cells. Furthermore, under NIR irradiation, BSArGO@ZIF8 NSs-mediated PTT could further kill cancer cells, and the increased temperature caused by photothermal conversion accelerated the Fenton reaction rate, enhancing the efficiency of BSArGO@ZIF8 NSs cell lethality. RNA-seq analysis confirmed that. BSArGO@ZIF8 NSs could promote cancer death through activate bim-mediated mitochondrial apoptotic events, induce disruption of microtubule function, loss of integrity of the nuclear membrane, DNA flagmentation, and change pro-apoptptic genes expression.
2023-12-01 | GSE191172 | GEO
Project description:Cancer cell membrane (CCM) derived nanotechnology functionalizes nanoparticles (NPs) to recognize homologous cells, exhibiting translational potential in accurate tumor therapy. However, these nanoplatforms are majorly generated from fixed cell lines and are typically evaluated in cell line-derived subcutaneous-xenografts (CDX), ignoring the tumor heterogeneity and differentiation from inter- and intra- individuals and microenvironments between heterotopic- and orthotopic-tumors, limiting the therapeutic efficiency of such nanoplatforms. Herein, various biomimetic nanoplatforms (CCM-modified gold@Carbon, i.e., Au@C-CCM) were fabricated by coating CCMs of head and neck squamous cell carcinoma (HNSCC) cell lines and patient-derived cells on the surface of Au@C NP. The generated Au@C-CCMs were evaluated on corresponding CDX, tongue orthotopic xenograft (TOX), immune-competent primary and distant tumor models, and patient-derived xenograft (PDX) models. The Au@C-CCM generates a photothermal conversion efficiency up to 44.2% for primary HNSCC therapy and induced immunotherapy to inhibit metastasis via photothermal therapy-induced immunogenic cell death. The homologous CCM endowed the nanoplatforms with optimal targeting properties for the highest therapeutic efficiency, far above those with mismatched CCMs, resulting in distinct tumor ablation and tumor growth inhibition in all four models. This work reinforces the feasibility of biomimetic NPs combining modular designed CMs and functional cores for customized treatment of HNSCC, can be further extended to other malignant tumors therapy.
| S-EPMC9918549 | biostudies-literature
Project description:Chemo-mild photothermal synergistic therapy can effectively inhibit tumor growth under mild hyperthermia, minimizing damage to nearby healthy tissues and skin while ensuring therapeutic efficacy. In this paper, we develop a multifunctional study based on polyhedral oligomeric sesquisiloxane (POSS) that exhibits a synergistic therapeutic effect through mild photothermal and chemotherapy treatments (POSS-SQ-DOX). The nanoplatform utilizes SQ-N as a photothermal agent (PTA) for mild photothermal, while doxorubicin (DOX) serves as the chemotherapeutic drug for chemotherapy. By incorporating POSS into the nanoplatform, we successfully prevent the aggregation of SQ-N in aqueous solutions, thus maintaining its excellent photothermal properties both in vitro and in vivo. Furthermore, the introduction of polyethylene glycol (PEG) significantly enhances cell permeability, which contributes to the remarkable therapeutic effect of POSS-SQ-DOX NPs. Our studies on the photothermal properties of POSS-SQ-DOX NPs demonstrate their high photothermal conversion efficiency (62.3%) and stability, confirming their suitability for use in mild photothermal therapy. A combination index value (CI = 0.72) verified the presence of a synergistic effect between these two treatments, indicating that POSS-SQ-DOX NPs exhibited significantly higher cell mortality (74.7%) and tumor inhibition rate (72.7%) compared to single chemotherapy and mild photothermal therapy. This observation highlights the synergistic therapeutic potential of POSS-SQ-DOX NPs. Furthermore, in vitro and in vivo toxicity tests suggest that the absence of cytotoxicity and excellent biocompatibility of POSS-SQ-DOX NPs provide a guarantee for clinical applications. Therefore, utilizing near-infrared light-triggering POSS-SQ-DOX NPs can serve as chemo-mild photothermal PTA, while functionalized POSS-SQ-DOX NPs hold great promise as a novel nanoplatform that may drive significant advancements in the field of chemo-mild photothermal therapy.
| S-EPMC10816201 | biostudies-literature
Project description:Plasmonic photothermal therapy (PPTT) using plasmonic nanoparticles as efficient photoabsorbing agents has been proposed previously. One critical step in PPTT is to effectively deliver gold nanoparticles into the cells. This study demonstrates that the delivery of gold nanorods (AuNRs) can be greatly enhanced by combining the following three mechanisms: AuNRs encapsulated in protein-shell microbubbles (AuMBs), molecular targeting, and sonoporation employing acoustic cavitation of microbubbles (MBs). Both in vitro and in vivo tests were performed. For molecular targeting, the AuMBs were modified with anti-VEGFR2. Once bound to the angiogenesis markers, the MBs were destroyed by ultrasound to release the AuNRs and the release was confirmed by photoacoustic measurements. Additionally, acoustic cavitation was induced during MB destruction for sonoporation (i.e., increase in transient cellular permeability). The measured inertial cavitation dose was positively correlated with the temperature increase at the tumor site. The quantity of AuNRs delivered into the cells was also determined by measuring the mass spectrometry and observed using third-harmonic-generation microscopy and two-photon fluorescence microscopy. A temperature increase of 20 °C was achieved in vitro. The PPTT results in vivo also demonstrated that the temperature increase (>45 °C) provided a sufficiently high degree of hyperthermia. Therefore, synergistic delivery of AuNRs was demonstrated.
| S-EPMC4097346 | biostudies-other
Project description:The biological barriers in vivo have limited the site-specific bioavailability and impeded therapeutic efficacy. To tackle these issues, nonspherical particles with a shape effect have attracted wide attention to affect the in vivo translocation of a drug delivery system. Herein, we constructed a nanoplatform based on polypyrrole (PPy) nanoneedles by hyaluronic acid (HA) modification and doxorubicin (DOX) loading. The PPy-HA@DOX nanoneedles with high aspect ratios could enhance the extravasation through the fenestrated vasculature of tumors, transport across tumor cell membrane via an endocytosis mechanism or even penetrated the membrane directly, and ultimately enter the nucleus easily via the nuclear pore complex by passive diffusion. With the ability of overcoming biological barriers, the PPy nanoneedle based nanoplatform would deliver drugs into the organelles more effectively. Under near infrared (NIR) laser irradiation, PPy as the photothermal agent could lead to tumor cellular structure damage for photothermal therapy (PTT). Therefore, PPy-HA@DOX developed here would exploit the merits of synergistic combination of chemo-photothermal therapy, which would pave the way toward more effective nanotherapeutics.
| S-EPMC9049910 | biostudies-literature
Project description:Noninvasive tumor therapy requires a new generation of bionanomaterials towards sensitive response to the unique tumor microenvironment to achieve accurate and effective treatment. Herein, we have developed a tumor therapy nanoplatform by immobilizing natural glucose oxidase (GOD) onto Cu-based layered double hydroxide (CuFe-LDH) nanosheets, which for the first time integrates acid-enhanced photothermal therapy (PTT), and pH-responsive and heat-facilitated chemodynamic therapy (CDT) simultaneously. As demonstrated by EXAFS and HRTEM, CuFe-LDH nanosheets possess a considerable number of defects caused by different acid conditions, resulting in a significantly acid-enhanced photothermal conversion efficiency (83.2% at pH 5.4 vs. 46.0% at pH 7.4). Moreover, GOD/CuFe-LDH nanosheets can convert a cascade of glucose into hydroxyl radicals (˙OH) under tumor acid conditions, which is validated by a high maximum velocity (V max = 2.00 × 10-7 M) and low Michaelis-Menten constant (K M = 12.01 mM). With the combination of PTT and CDT, the tumor tissue in vivo is almost eliminated with low-dose drug injection (1 mg kg-1). Therefore, this novel pH-responsive Cu-based nanoplatform holds great promise in tumor-specific CDT/PTT synergistic therapy.
| S-EPMC8179329 | biostudies-literature
Project description:Synergistic photothermal therapy (PTT) and chemotherapy is an efficient strategy for tumor therapy. However, it is still a challenge to design a smart delivery system able to release a drug at the appropriate time and site of action. Here, we have synthesized photosensitive molecule 7-(double dodecylamine)-4-hydroxymethylcoumarin which was introduced in a nanocarrier GNR@SiO2-DOX@CouC12-HA (GSDCH) to achieve manually controlled drug release. The specific nanocarrier was fabricated using a GNR core for photothermal therapy, a mesoporous silica shell for drug loading, and the coumarin moiety as a blocking agent and intelligent controlled switch. In addition, cellular uptake of GSDCH by HeLa cells can be achieved effectively with the help of hyaluronic acid (HA). Owing to the controlled and targeted drug release properties, the GSDCH with photothermal- and chemo-therapy showed significantly enhanced therapeutic efficiency for HeLa tumor-bearing mice compared to the results of single therapy alone. It indicated that the GSDCH had great potential in tumor therapy with negligible systematic toxicity.
| S-EPMC9091941 | biostudies-literature
Project description: Not available
| S-EPMC10668414 | biostudies-literature