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Gambogic Acid Augments Black Phosphorus Quantum Dots (BPQDs)-Based Synergistic Chemo-Photothermal Therapy through Downregulating Heat Shock Protein Expression
摘要： In an attempt to attain synergistic therapeutic benefits and address various intrinsic limitations of the highly efficient black phosphorus quantum dots (BPQDs), we fabricated poly(L-lactide)-poly(ethylene glycol)-poly(L-lactide) triblock copolymer (PLLA-PEG-PLLA)-based nanocomposites co-loaded with BPQDs and gambogic acid (GA) using the supercritical carbon dioxide (SC-CO2) technology to achieve photoacoustic (PA) imaging-guided synergistic chemo-photothermal therapy. On the one hand, BPQDs displayed near-infrared (NIR)-induced hyperthermia through the high photothermal conversion efficiency. On the other hand, the NIR-responsive release of GA facilitated early apoptosis through specific binding to stress-induced overexpression of heat shock protein (HSP)-90 for combating thermoresistant tumor cells. GA significantly promoted the photothermal therapy (PTT) efficiency by enhancing both early and late apoptosis of BPQDs. Moreover, the encapsulation of BPQDs in the polymer significantly improved their chemical as well as photothermal stabilities. Our findings suggested that these nanocomposites fabricated using the eco-friendly supercritical fluid (SCF) technology provided good protection to the biodegradable BPQDs, offering a great potential towards cancer ablation through augmented synergistic effects.
关键词： Synergism,NIR-responsive,Black phosphorus,Heat shock protein,Photothermal therapy
更新于2025-09-19 17:13:59
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Quercetin encapsulated biodegradable plasmonic nanoparticles for photothermal therapy of hepatocellular carcinoma cells
摘要： Photothermal therapy (PTT) is emerging as an effective treatment modality for cancer due to its non-invasive nature. However, the pro-inflammatory necrotic cell death during PTT limits its successful clinical application. Here, we have developed quercetin (QE) loaded biodegradable plasmonic nanoparticles that can specifically induce apoptosis in cancer cells after PTT. We have synthesized gold-coated liposome (LiposAu) and QE loaded gold-coated liposome (QE-LiposAu) nanoparticles by in situ reduction of chloroauric acid with ascorbic acid in the presence of bare liposomes (Lipos) or QE loaded liposomes (QE-Lipos), respectively. The gold coating was confirmed by transmission electron microscopic analysis, dynamic light scattering, and zeta potential measurements. LiposAu and QE-LiposAu nanoparticles showed a similar level of temperature rise upon 750 nm near-infrared (NIR) laser (650 mW, 3 W cm-2) irradiation. The photothermal conversion efficiency of QE-LiposAu nanoparticles was determined to be ~75%. The efficacy of PTT was found to be dependent on the internalization efficiency of LiposAu nanoparticles in cancer cells. Importantly, QE-LiposAu nanoparticles showed increased PTT efficacy over LiposAu nanoparticles in hepatocellular carcinoma cells (Huh-7). Moreover, QE-LiposAu nanoparticles induced apoptosis-mediated cell death after the PTT, and the extent of apoptosis was significantly higher than the LiposAu nanoparticles in Huh-7 cells. Further, QE-LiposAu nanoparticles-mediated PTT depolymerized microtubules network, suppressed Hsp70 expression, and caused DNA damage. QE-LiposAu nanoparticles were also found to be hemocompatible. The results together suggested that biodegradable QE-LiposAu nanoparticles are promising photothermal agents for cancer therapy.
关键词： heat shock protein,liposome,microtubule,apoptosis,gold nanoparticles,DNA damage,Photothermal therapy
更新于2025-09-12 10:27:22
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Targeted near infrared hyperthermia combined with immune stimulation for optimized therapeutic efficacy in thyroid cancer treatment
摘要： Treatment of thyroid cancer has incurred much focus because of its high prevalency. As a new strategy treating thyroid cancer, hyperthermia takes several advantages compared with surgery or chemotherapy, including minimal invasion, low systematic toxicity and the ability to enhance the immunogenicity of cancer cells with the expression Hsp70 which serves as Toll-like receptors-4 (TLR-4 agonist). However, Hsp70 as a molecular chaperone can protect cells from heat induced apoptosis and therefore compromise the tumor killing effect of hyperthermia. In this study, to solve this problem, a combined hyperthermia therapy was employed to treat thyroid cancer. We prepared a probe with the tumor targeting agent AG to monitor thyroid tumor issue and generate heat to kill tumor cells in vivo. At the same time Quercetin (inhibitor of HSP70) and lipopolysaccharide (LPS) (agonist of TLR-4) were used for the combined hyperthermia therapy. The results showed that compared with free IR820, AG modification facilitated much enhanced cellular uptake and greatly pronounced tumor targeting ability. The combined therapy exhibited the most remarkable tumor inhibition compared with the single treatments both in vitro and in vivo. These findings verified that the new therapeutic combination could significantly improve the effect of hyperthermia and shed light on a novel clinical strategy in thyroid cancer treatment.
关键词： IR820,amino-glucose,near infrared hyperthermia,tumor targeting,heat shock protein 70
更新于2025-09-09 09:28:46