- 标题
- 摘要
- 关键词
- 实验方案
- 产品
-
Two-photon excited organic nanoparticles for chemo-photodynamic therapy
摘要： Drug molecules assembling nanomedicines possess several advantages, including precise molecular structure, various combinations of theraputic agents and high content of drugs. In this work, paclitaxel dimer and two-photo photosensitizer were devised and synthesized, which could coassemble into nanoparticles (Co-NPs) in aqueous medium through nanopreicipitation method. As-synthesized Co-NPs possess the uniform size of about 80 nm and great stability in physiological condition, and could produce the singlet oxygen upon near-infrared light irradiation. The Co-NPs indicate enhanced cellular uptake and endosomal escape upon irradiation, which result in the synergistic enhancement of cytotoxicity towards cancer cells and growth inhibition of human cervical cancer tumors. We believed this combination therapy based on organic nanoparticles represent a new and important development in the cancer therapy.
关键词： two-photon,photodynamic therapy,paclitaxel,chemotherapy
更新于2025-11-21 11:08:12
-
A personalized and long-acting local therapeutic platform combining photothermal therapy and chemotherapy for the treatment of multidrug-resistant colon tumor
摘要： Background: Local photothermal therapy (PTT) provides an easily applicable, noninvasive adjunctive therapy for colorectal cancer (CRC), especially when multidrug resistance (MDR) occurs. However, using PTT alone does not result in complete tumor ablation in many cases, thus resulting in tumor recurrence and metastasis. Materials and methods: In this study, we aim to develop a personalized local therapeutic platform combining PTT with long-acting chemotherapy for the treatment of MDR CRC. The platform consists of polyethylene glycol (PEG)-coated gold nanorods (PEG-GNRs) and d-alpha-tocopheryl PEG 1000 succinate (TPGS)-coated paclitaxel (PTX) nanocrystals (TPGS-PTX NC), followed by the incorporation into an in situ hydrogel (gel) system (GNRs-TPGS-PTX NC-gel) before injection. After administration, PEG-GNRs can exert quick and efficient local photothermal response under near-infrared laser irradiation to shrink tumor; TPGS-PTX NC then provides a long-acting chemotherapy due to the sustained release of PTX along with the P-glycoprotein inhibitor TPGS to reverse the drug resistance. Results: The cytotoxicity studies showed that the IC50 of GNRs-TPGS-PTX NC-gel with laser irradiation decreased to ~178-folds compared with PTX alone in drug-resistant SW620 AD300 cells. In the in vivo efficacy test, after laser irradiation, the GNRs-TPGS-PTX NC-gel showed similar tumor volume inhibition compared with GNRs-gel at the beginning. However, after 14 days, the tumor volume of the mice treated with GNRs-gel quickly increased, while that of the mice treated with GNRs-TPGS-PTX NC-gel remained controllable due to the long-term chemotherapeutic effect of TPGS-PTX NC. The mice treated with GNRs-TPGS-PTX NC-gel also showed no weight loss and obvious organ damages and lesions during the treatment, indicating a low systemic side effect profile and a good biocompatibility. Conclusion: Overall, the nano-complex may serve as a promising local therapeutic patch against MDR CRC with one-time dosing to achieve a long-term tumor control. The doses of PEG-GNRs and TPGS-PTX NC can be easily adjusted before use according to patient-specific characteristics potentially making it a personalized therapeutic platform.
关键词： in situ hydrogel,tumor recurrence,gold nanorods,paclitaxel nanocrystals,TPGS
更新于2025-09-23 15:23:52
-
Histology and antitumor activity study of PTX-loaded micelle, a fluorescent drug delivery system prepared by PEG-TPP
摘要： We synthesized PEG-TPP as carrier to encapsulate paclitaxel (PTX) in the form of micelles to overcome its water-solubility problem. PTX-loaded micelles possess a-week stability and appropriate particle size (152.1±1.2 nm) which is beneficial for enhanced permeability and retention (EPR) effect. Strong pH dependence of PTX releasing from micelles is verified by in vitro release study. At cellular level, PTX-loaded micelles can target mitochondria effectively which may results a better cytotoxicity of micelles (especially IC50 = 0.123±0.035 μmol/L of micelles and 0.298±0.067 μmol/L of PTX alone on MCF-7 cells). The fluorescence distributions of both isolated and sliced organs show that the micelles can effectively target tumors. Moreover, we further prove the enhanced therapeutic effects of micelles in tumor-bearing mice comparing with PTX alone. The results show that the biodegradable drug delivery system prepared by PEG-TPP can overcome the poor solubility of paclitaxel and improve its tumor targeting and antitumor activity.
关键词： PEG-TPP,Mitochondria,Paclitaxel,EPR,Micelles,Anticancer
更新于2025-09-23 15:22:29
-
Photoacoustic Imaging Quantifies Drug Release from Nanocarriers via Redox Chemistry of Dye‐Labeled Cargo
摘要： There have been remarkable advances in imaging drug nanocarriers, but there are few real-time imaging strategies to determine if the cargo has been released from the carrier. This is important because the pharmacokinetics and pharmacodynamics of the carrier can often be dramatically decoupled from that of the cargo. Thus, new tools are clearly needed to image the timing and quantity of drug release from nanocarriers. Here, we describe a simple strategy for photoacoustic monitoring of drug release based on the redox chemistry of methylene blue, which offers predictable redox chemistry: It can transition from the oxidized state with a bright blue color and robust photoacoustic signal to the reduced state that the transparent with no photoacoustic signal. We locked this drug-dye conjugate into a reduced state inside of a nanoparticle with no photoacoustic signal. As the drug is released from the carrier, the dye is oxidized for quantification with photoacoustic imaging. We first prepared paclitaxel-methylene blue conjugate (PTX-MB) with strong absorbance at 640 nm and photoacoustic intensity proportional to its concentration. This cargo was co-encapsulated in a poly(lactic-co-glycolic acid) nanoparticle with a dithiothreitol reducing agent. The IC50 of PTX-MB-loaded NPs (PTX-MB @ PLGA NPs) was 78 μg mL-1. We then used the redox reaction of PTX-MB to monitor its release from poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). In vitro drug-release in phosphate buffer saline with 20% v/v normal mice serum showed a 670-fold increase in photoacoustic signal. The particles showed an initial burst release (25%) during the first 24 hours. After 24 hours, a sustained release was observed through 120 hours leading to cumulative release of 40.6% of PTX-MB. In vivo drug release study in mice for a duration of 12 hours showed a photoacoustic signal enhancement of up to 649% after 10 hours. We then used this system to treat an orthotopic model of colon cancer via luciferase-positive CT26 cells. Our data showed that tumor burden decreased by 44.7% ± 4.8% when treated with the PTX-MB @ PLGA NPs versus the empty PLGA carrier. This work presents a direct strategy to simultaneously monitor drug release biodistribution.
关键词： Photoacoustic imaging,Paclitaxel,Image-guided drug delivery,PLGA nanoparticles,Drug-release,Cancer therapy,in vivo monitoring
更新于2025-09-16 10:30:52
-
Laser atherectomy and drug‐coated balloons for the treatment of femoropopliteal in‐stent restenosis: 2‐Year outcomes
摘要： Background: Femoropopliteal (FP) artery is one of the most anatomically challenging areas for sustained stent patency. The incidence of FP in-stent restenosis (ISR) is estimated at 50% at 24 months. Prior studies have shown that lesion debulking with laser atherectomy (LA) combined with drug coated balloon (DCB) have superior outcomes compared to LA + balloon angioplasty (BA) ISR, but there have not been studies evaluating 2-year outcomes. Methods: This was a dual-center retrospective cohort study that compared patients with FP-ISR treated with LA + DCB versus LA + BA. Cox regression analysis was used to examine 2-year outcomes of target lesion revascularization (TLR) and the composite outcome of TLR or restenosis. Multivariable analysis was performed for clinical and statistically significant (in the univariate analysis) variables. Results: One hundred and seventeen consecutive patients with Tosaka II (n = 32) and III (n = 85) ISR were analyzed. Sixty-six patients were treated with LA + DCB and 51 with LA + BA. The LA + DCB group had more lesions with moderate to severe calcification (58% vs. 13%; p < .0001). The LA + DCB group was more likely to be treated with the use of embolic protection devices (64% vs. 23%, p < .001) and cutting balloons (61% vs. 6%, p < .001). Bail-out stenting rates were lower in the LA + DCB group (32% vs. 57%, p = .008). LA + DCB was superior (HR: 0.57; 95% CI: 0.34–0.9, p = .027) for the composite outcome of 2-year TLR or restenosis. The 12-month KM estimates for freedom from TLR or restenosis were 66% in the LA + DCB group versus 46% in the LA + BA group. The 24-month KM estimates were 45% in the LA + DCB group versus 24% in the LA + BA group. Conclusions: The combination of DCB + LA was associated with decreased rates of bail-out stenting and improved 2-year TLR or restenosis rates. Randomized clinical trials examining the DCB + LA combination for FP-ISR are needed.
关键词： femoropopliteal disease,drug-coated balloon,chronic total occlusions,peripheral artery disease,paclitaxel,laser,atherectomy,in-stent restenosis
更新于2025-09-12 10:27:22
-
P2636Comparison of the efficacy of balloon angioplasty or paclitaxel-coated balloon or stent implantation for in-stent restenosis based on analysis by optical coherence tomography
摘要： We could distinguish the restenotic tissue structure patterns in detail by optical coherence tomography (OCT). We hypothesized that the recurrent restenosis of the in-stent restenosis (ISR) lesions might be different among restenotic tissue structure patterns analyzed by OCT. The purpose of this study was to investigate the efficacy of balloon angioplasty (BA) or paclitaxel-coated balloon (PCB) or stent implantation (SI) for the treatment of the in-stent restenosis (ISR) based on the restenotic tissue structure analyzed by optical coherence tomography (OCT). From January 2010 to September 2016, we evaluated 330 patients with 365 ISR lesions that required revascularization (281 drug-eluting stents (DES) and 84 bare-metal stents (BMS)). Based on their OCT appearance at the minimum lumen area, the lesions were classified as homogeneous and non-homogeneous. We compared recurrent target lesion revascularization (TLR) at 1year follow-up after BA or PCB or SI. By OCT, the restenotic tissue structure was homogeneous in 149 (41%) and non-homogeneous in 216 (59%). In homogeneous group, 55 patients had BA, 45 patients had PCB and 49 patients had SI. In non-homogeneous group, 87 patients had BA, 50 patients had PCB and 79 patients had SI. Angiographic follow-up after TLR was performed in 263 patients (80%) with 294 lesions (81%) at 1 year. As OCT appeared homogeneous, recurrent TLR was noted in 22% of BA group, in 13% of PCB group and in 16% of SI group (p=0.5). As OCT appeared non-homogeneous, recurrent TLR occurred in 33% of BA group, in 14% of PCB group and in 13% of SI group (p=0.002). We concluded that morphological assessment of restenotic tissue by OCT might be helpful to decide the treatment strategies of ISR.
关键词： imaging,paclitaxel-coated balloon,balloon angioplasty,Stents,stent implantation,Coronary interventions,in-stent restenosis,optical coherence tomography,Coronary physiology
更新于2025-09-10 09:29:36
-
Specific Targeting of Breast Cancer Cells with Antibodies Conjugated Gold Nanoparticles
摘要： Background and Objective: Gold nanoparticles (AuNP) conjugated with either EpCAM or TARP antibodies and an anticancer agent, paclitaxel (PTX), for tumour targeting and therapy were synthesised using a simple chemistry. Methods: The AuNP surface was functionalised using a two-step modification approach. The conjugates were characterised using Transmission Electron Microscopy (TEM) and infrared spectroscopy. Results: The cytotoxicity assay of T47D cells treated with only antibodies conjugated to the gold nanoparticles did not show any cytotoxicity to the cells, which indicates these nanoconjugates are suitable for intracellular delivery of anticancer drugs. Conclusion: When using AuNPs with antibodies and the cancer chemotherapy agent PTX attached simultaneously to the functionalised AuNPs, the reduction of cell viability was significantly higher compared to PTX-thiol-AuNPs conjugate system where no antibodies were used.
关键词： drug delivery,antibodies,paclitaxel,EpCAM,Gold nanoparticles,TARP,cytotoxicity
更新于2025-09-04 15:30:14