Integrin αvβ3-targeted polydopamine-coated gold nanostars for photothermal ablation therapy of hepatocellular carcinoma.
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ABSTRACT:
SUBMITTER: Li Y
PROVIDER: S-EPMC8387661 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The combination of photothermal therapy with chemotherapy has gradually developed into promising cancer therapy. Here, a synergistic photothermal-chemotherapy nanoplatform based on polydopamine (PDA)-coated gold nanoparticles (AuNPs) were facilely achieved via the in situ polymerization of dopamine (DA) on the surface of AuNPs. This nanoplatform exhibited augmented photothermal conversion efficiency and enhanced colloidal stability in comparison with uncoated PDA shell AuNPs. The i-motif DNA nanostructure was assembled on PDA-coated AuNPs, which could be transformed into a C-quadruplex structure under an acidic environment, showing a characteristic pH response. The PDA shell served as a linker between the AuNPs and the i-motif DNA nanostructure. To enhance the specific cellular uptake, the AS1411 aptamer was introduced to the DNA nanostructure employed as a targeting ligand. In addition, Dox-loaded NPs (DAu@PDA-AS141) showed the pH/photothermal-responsive release of Dox. The photothermal effect of DAu@PDA-AS141 elicited excellent photothermal performance and efficient cancer cell inhibition under 808 nm near-infrared (NIR) irradiation. Overall, these results demonstrate that the DAu@PDA-AS141 nanoplatform shows great potential in synergistic photothermal-chemotherapy.
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Project description:Inflammatory breast cancer (IBC) is rare, but it is the most aggressive subtype of breast cancer. IBC has a unique presentation of diffuse tumor cell clusters called tumor emboli in the dermis of the chest wall that block lymph vessels causing a painful, erythematous, and edematous breast. Lack of effective therapeutic treatments has caused mortality rates of this cancer to reach 20%-30% in case of women with stage III-IV disease. Plasmonic nanoparticles, via photothermal ablation, are emerging as lead candidates in next-generation cancer treatment for site-specific cell death. Plasmonic gold nanostars (GNS) have an extremely large two-photon luminescence cross-section that allows real-time imaging through multiphoton microscopy, as well as superior photothermal conversion efficiency with highly concentrated heating due to its tip-enhanced plasmonic effect. To effectively study the use of GNS as a clinically plausible treatment of IBC, accurate three-dimensional (3D) preclinical models are needed. Here, we demonstrate a unique in vitro preclinical model that mimics the tumor emboli structures assumed by IBC in vivo using IBC cell lines SUM149 and SUM190. Furthermore, we demonstrate that GNS are endocytosed into multiple cancer cell lines irrespective of receptor status or drug resistance and that these nanoparticles penetrate the tumor embolic core in 3D culture, allowing effective photothermal ablation of the IBC tumor emboli. These results not only provide an avenue for optimizing the diagnostic and therapeutic application of GNS in the treatment of IBC but also support the continuous development of 3D in vitro models for investigating the efficacy of photothermal therapy as well as to further evaluate photothermal therapy in an IBC in vivo model.
| S-EPMC5584896 | biostudies-literature
Project description:Au nanorods (AuNRs) have attracted a great interest as a platform for constructing various composite core/shell nanoparticles for theranostics applications. However, the development of robust methods for coating AuNRs with a biocompatible shell of high loading capacity and with functional groups still remains challenging. Here, we coated AuNRs with a polydopamine (PDA) shell and functionalized AuNR-PDA particles with folic acid and rhodamine 123 (R123) to fabricate AuNR-PDA-R123-folate nanocomposites. To the best of our knowledge, such AuNR-PDA-based composites combining fluorescent imaging and plasmonic phothothermal abilities have not been reported previously. The multifunctional nanoparticles were stable in cell buffer, nontoxic and suitable for targeted fluorescent imaging and photothermal therapy of cancer cells. We demonstrate the enhanced accumulation of folate-functionalized nanoparticles in folate-positive HeLa cells in contrast to the folate-negative HEK 293 cells using fluorescent microscopy. The replacement of folic acid with polyethylene glycol (PEG) leads to a decrease in nanoparticle uptake by both folate-positive and folate-negative cells. We performed NIR light-mediated targeted phototherapy using AuNR-PDA-R123-folate and obtained a remarkable cancer cell killing efficiency in vitro in comparison with only weak-efficient nontargeted PEGylated nanoparticles. Our work illustrates that AuNR-PDA could be a promising nanoplatform for multifunctional tumor theranostics in the future.
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Project description:Recent studies have highlighted the overexpression of mucin 1 (MUC1) in various epithelial carcinomas and its role in tumorigenesis. These mucins present a novel targeting opportunity for nanoparticle-mediated photothermal cancer treatments due to their unique antenna-like extracellular extension. In this study, MUC1 antibodies and albumin were immobilized onto the surface of gold nanorods using a "primer" of polydopamine (PD), a molecular mimic of catechol- and amine-rich mussel adhesive proteins. PD forms an adhesive platform for the deposition of albumin and MUC1 antibodies, achieving a surface that is stable, bioinert and biofunctional. Two-photon luminescence confocal and darkfield scattering imaging revealed targeting of MUC1-BSA-PD-NRs to MUC1+ MCF-7 breast cancer and SCC-15 squamous cell carcinoma cells lines. Treated cells were exposed to a laser encompassing the near-infrared AuNR longitudinal surface plasmon and assessed for photothermal ablation. MUC1-BSA-PD-NRs substantially decreased cell viability in photoirradiated MCF-7 cell lines vs. MUC1- MDA-MB-231 breast cancer cells (p < 0.005). Agents exhibited no cytotoxicity in the absence of photothermal treatment. The facile nature of the coating method, combined with targeting and photoablation efficacy, are attractive features of these candidate cancer nanotherapeutics.
| S-EPMC4493038 | biostudies-literature
Project description:BackgroundGold nanostars are unique nanoplatforms that can be imaged in real time and transform light energy into heat to ablate cells. Adipose-derived stem cells migrate toward tumor niches in response to chemokines. The ability of adipose-derived stem cells to migrate and integrate into tumors makes them ideal vehicles for the targeted delivery of cancer nanotherapeutics.MethodsTo test the labeling efficiency of gold nanostars, undifferentiated adipose-derived stem cells were incubated with gold nanostars and a commercially available nanoparticle (Qtracker), then imaged using two-photon photoluminescence microscopy. The effects of gold nanostars on cell phenotype, proliferation, and viability were assessed with flow cytometry, 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide metabolic assay, and trypan blue, respectively. Trilineage differentiation of gold nanostar-labeled adipose-derived stem cells was induced with the appropriate media. Photothermolysis was performed on adipose-derived stem cells cultured alone or in co-culture with SKBR3 cancer cells.ResultsEfficient uptake of gold nanostars occurred in adipose-derived stem cells, with persistence of the luminescent signal over 4 days. Labeling efficiency and signal quality were greater than with Qtracker. Gold nanostars did not affect cell phenotype, viability, or proliferation, and exhibited stronger luminescence than Qtracker throughout differentiation. Zones of complete ablation surrounding the gold nanostar-labeled adipose-derived stem cells were observed following photothermolysis in both monoculture and co-culture models.ConclusionsGold nanostars effectively label adipose-derived stem cells without altering cell phenotype. Once labeled, photoactivation of gold nanostar-labeled adipose-derived stem cells ablates neighboring cancer cells, demonstrating the potential of adipose-derived stem cells as a vehicle for the delivery of site-specific cancer therapy.
| S-EPMC5373491 | biostudies-literature
Project description:The combination of photothermal therapy (PTT) and photodynamic therapy (PDT) in cancer treatment has attracted much attention in recent years. However, developing highly efficient and targeted therapeutic nanoagents for amplifying PTT and PDT treatments remains challenging. In this work, we developed a novel photothermal and photodynamic therapeutic nanoplatform for treatment of cancer cells overexpressing integrin ?v?? through the coating of polydopamine (PDA) on indocyanine green (ICG)-loaded laponite (LAP) and then further conjugating polyethylene glycol-arginine-glycine-aspartic acid (PEG-RGD) as targeted agents on the surface. The ICG/LAP?PDA?PEG?RGD (ILPR) nanoparticles (NPs) formed could load ICG with a high encapsulation efficiency of 94.1%, improve the photostability of loaded ICG dramatically via the protection of PDA and LAP, and display excellent colloidal stability and biocompatibility due to the PEGylation. Under near-infrared (NIR) laser irradiation, the ILPR NPs could exert enhanced photothermal conversion reproducibly and generate reactive oxygen species (ROS) efficiently. More importantly, in vitro experiments proved that ILPR NPs could specifically target cancer cells overexpressing integrin ?v??, enhance cellular uptake due to RGD-mediated targeting, and exert improved photothermal and photodynamic killing efficiency against targeted cells under NIR laser irradiation. Therefore, ILPR may be used as effective therapeutic nanoagents with enhanced photothermal conversion performance and ROS generating ability for targeted PTT and PDT treatment of cancer cells with integrin ?v?? overexpressed.
| S-EPMC5977361 | biostudies-literature
Project description:AimA novel biomimetic strategy was employed for presenting antibodies on gold nanorods (NRs) to target growth factor receptors on cancer cells for use in photothermal therapy.Materials & methodsPolydopamine (PD) was polymerized onto gold NRs, and EGF receptor antibodies (anti-EGFR) were immobilized onto the layer. Cell-binding affinity and light-activated cell death of cancer cells incubated with anti-EGFR-PD-NRs were quantified by optical imaging.ResultsPD was deposited onto gold NRs, and antibodies were bound to PD-coated NRs. Anti-EGFR-PD-NRs were stable in media, and were specifically bound to EGFR-overexpressing cells. Illumination of cells targeted with anti-EGFR-PD-NRs enhanced cell death compared with nonirradiated controls and cells treated with antibody-free NRs.ConclusionPD facilitates the surface functionalization of gold NRs with biomolecules, allowing cell targeting and photothermal killing of cancer cells. PD can potentially coat a large variety of nanoparticles with targeting ligands as a strategy for biofunctionalization of diagnostic and therapeutic nanoparticles.
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Project description:Surface-enhanced Raman scattering (SERS) is becoming widely used as an analytical tool, and the search for stable and highly responsive SERS substrates able to give ultralow detection of pollutants is a current challenge. In this paper we boosted the SERS response of Gold nanostars (GNS) demonstrating that their coating with a layer of silver having a proper thickness produces a 7-fold increase in SERS signals. Glass supported monolayers of these GNS@Ag were then prepared using simple alcoxyliane chemistry, yielding efficient and reproducible SERS chips, which were tested for the detection of molecules representative of different classes of pollutants. Among them, norfloxacin was detected down to 3 ppb, which is one of the lowest limits of detection obtained with this technique for the analyte.
| S-EPMC9609606 | biostudies-literature
Project description:Bacteria infections and related biofilms growth on surfaces of medical devices are a serious threat to human health. Controlled hyperthermia caused by photothermal effects can be used to kill bacteria and counteract biofilms formation. Embedding of plasmonic nano-objects like gold nanostars (GNS), able to give an intense photothermal effect when irradiated in the NIR, can be a smart way to functionalize a transparent and biocompatible material like polydimethylsiloxane (PDMS). This process enables bacteria destruction on surfaces of PDMS-made medical surfaces, an action which, in principle, can also be exploited in subcutaneous devices. We prepared stable and reproducible thin PDMS films containing controllable quantities of GNS, enabling a temperature increase that can reach more than 40 degrees. The hyperthermia exerted by this hybrid material generates an effective thermal microbicidal effect, killing bacteria with a near infrared (NIR) laser source with irradiance values that are safe for skin.
| S-EPMC8707359 | biostudies-literature
Project description:Photothermal therapy (PTT) can be an effective antitumor therapy, but it may not completely eliminate tumor cells, leading to the risk of recurrence or metastasis. Here we describe nanocarriers that allow combination therapy involving PTT and immunotherapy. Nanocarriers are prepared by coating Al2O3 nanoparticles with non-toxic, biodegradable polydopamine, which shows high photothermal efficiency. A near-infrared laser irradiation can kill the majority of tumor tissues, resulting in the release of tumor-associated antigens. The Al2O3 within the nanoparticles, together with CpG, acts as an adjuvant to trigger robust cell-mediated immune responses that can help eliminate the residual tumor cells and reduce the risk of tumor recurrence. Methods: The characteristics and photothermal performance of polydopamine-coated Al2O3 nanoparticles were examined after one-step preparation. Then we studied their internalization, photothermal toxicity and immunostimulatory activity in vitro. For in vivo experiments, these nanocarriers were injected directly into B16F10 melanoma allografts in mice to ensure specific localization. After photothermal irradiation on day 0, mice were subcutaneously injected with CpG adjuvant on day 1, 3 and 5. Tumor volumes and number of living mice were recorded every two days. Moreover, various immune responses induced by our combined therapy were tested for mechanism research. Results: 50% of mice after our combined treatment successfully achieved the goal of tumor eradication, and survived for 120 days, which was the end point of the experiment. Mechanism studies demonstrated the combined therapy efficiently led to dendritic cell maturation, resulting in the secretion of antibodies and cytokines as well as the proliferation of splenocytes and lymphocytes for anti-tumor immunotherapy. Conclusion: Taken together, these results demonstrated the promise of our combined photothermal therapy and immunotherapy for tumor shrinkage, which merited further research.
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