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Drug Delivery Dec 2022Breast cancer is one of the most common types of cancer in female patients with high morbidity and mortality. Multi-drug chemotherapy has significant advantages in the...
Breast cancer is one of the most common types of cancer in female patients with high morbidity and mortality. Multi-drug chemotherapy has significant advantages in the treatment of malignant tumors, especially in reducing drug toxicity, increasing drug sensitivity and reducing drug resistance. The objective of this research is to fabricate lipid nanoemulsions (LNs) for the co-delivery of PTX and docosahexaenoic acid (DHA) with folic acid (FA) decorating (PTX/DHA-FA-LNs), and investigate the anti-tumor activity of the PTX/DHA-FA-LNs against breast cancer both and . PTX/DHA-FA-LNs showed a steady release of PTX and DHA from the drug delivery system (DDS) without any burst effect. Furthermore, the PTX/DHA-FA-LNs exhibited a dose-dependent cytotoxicity and a higher rate of apoptosis as compared with the other groups in MCF-7 cells. The cellular uptake study revealed that this LNs were more readily uptaken by MCF-7 cells and M2 macrophages . Additionally, the targeted effect of PTX/DHA-FA-LNs was aided by FA receptor-mediated endocytosis, and its cytotoxicity was proportional to the cellular uptake efficiency. The anti-tumor efficiency results showed that PTX/DHA-FA-LNs significant inhibited tumor volume growth, prolonged survival time, and reduced toxicity when compared with the other groups. These results indicated that DHA increases the sensitivity of tumor cells and tumor-associated macrophages (ATM2) to PTX, and synergistic effects of folate modification in breast cancer treatment, thus PTX/DHA-FA-LNs may be a promising nanocarrier for breast cancer treatment.
Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Cell Line, Tumor; Cell Survival; Dose-Response Relationship, Drug; Drug Carriers; Drug Liberation; Emulsions; Female; Folic Acid; Humans; MCF-7 Cells; Mice; Mice, Inbred BALB C; Mice, Nude; Nanoparticles; Paclitaxel; RAW 264.7 Cells; Tumor-Associated Macrophages; Xenograft Model Antitumor Assays
PubMed: 34964421
DOI: 10.1080/10717544.2021.2018523 -
Signal Transduction and Targeted Therapy Jan 2021
Topics: Biomimetics; Drug Delivery Systems; Humans; Molecular Targeted Therapy; Neoplasms; Paclitaxel
PubMed: 33504772
DOI: 10.1038/s41392-020-00390-6 -
Medicine Dec 2022This paper aims to compare the effectiveness and safety of pembrolizumab and paclitaxel as a second line for patients with locally advanced gastroesophageal cancer. (Meta-Analysis)
Meta-Analysis
BACKGROUND
This paper aims to compare the effectiveness and safety of pembrolizumab and paclitaxel as a second line for patients with locally advanced gastroesophageal cancer.
METHODS
By searching PubMed, Scopus, Web of Science, and Ovid, any randomized clinical study comparing the effectiveness of paclitaxel and pembrolizumab as second-line therapy for advanced gastroesophageal cancer met the inclusion criteria. Only 3 of the 23 eligible studies that were fully reviewed were eligible for meta-analysis.
RESULTS
The total number of patients included in the meta-analysis was 635 in the pembrolizumab group and 596 in the paclitaxel group. In terms of objective response rate, there was no statistically significant difference between pembrolizumab and paclitaxel (relative risk = 1.10, 95% CI = 0.80-1.50, P = .57). Furthermore, Pembrolizumab and paclitaxel did not differ in terms of the rate of partial response statistically significantly from one another, according to the overall analysis (relative risk = 0.93, 95% CI = 0.57-1.52, P-value = .78).
CONCLUSION
There is no difference between pembrolizumab and paclitaxel in objective response rate. The objective response rate shows that doctors may consider either treatment for patients with advanced gastroesophageal cancer, given the time to response is comparable across therapies.
Topics: Humans; Paclitaxel; Randomized Controlled Trials as Topic; Neoplasms
PubMed: 36482610
DOI: 10.1097/MD.0000000000031940 -
Drug Delivery Dec 2022Albumin-bound paclitaxel (abPTX) has been widely used in cancer treatment. However, dose-related side effects, such as myelosuppression, restrict its clinical...
Albumin-bound paclitaxel (abPTX) has been widely used in cancer treatment. However, dose-related side effects, such as myelosuppression, restrict its clinical application. Cell-based targeting drug delivery is a promising way to mitigate systematic side-effects and improve antitumoral efficacy. In this study, we demonstrated that reassembled abPTX could be engulfed by neutrophils and delivered to tumor site, thus improving therapeutic efficacy and mitigating myelosuppression. First, analysis confirmed that reassembling of abPTX formed uniform and stable serum albumin nanoparticles (NP-abPTX) with size of 107.5 ± 2.29 nm and reserved the ability to kill tumor cells. Second, we found that NP-abPTX could be engulfed by activated neutrophil and but do not affect neutrophils' function, such as chemotaxis and activation. In a murine tumor model, we further proved that local radiotherapy (RT) induced inflammation activated peripheral neutrophils to capture venous infused NP-abPTX and carry them into tumor tissue. As compared to abPTX, infusion of NP-abPTX dramatically enhanced inhibition of tumor growth treated by local RT and mitigated hematotoxicity. Therefore, our study demonstrated a novel strategy to mitigate side-effects and to improve tumor killing efficacy of abPTX through neutrophil-mediated targeting drug delivery.
Topics: Albumin-Bound Paclitaxel; Animals; Cell Line, Tumor; Drug Delivery Systems; Mice; Nanoparticles; Neutrophils; Paclitaxel
PubMed: 35244505
DOI: 10.1080/10717544.2022.2046892 -
Advances in Clinical and Experimental... Dec 2021Drug resistance poses a crucial problem in the treatment of prostate cancer. Recent studies have shown that chemotherapy agents may cause cancer cells to acquire stem...
BACKGROUND
Drug resistance poses a crucial problem in the treatment of prostate cancer. Recent studies have shown that chemotherapy agents may cause cancer cells to acquire stem cell-like properties, resulting in drug resistance and, eventually, treatment failure.
OBJECTIVES
To evaluate whether long-term paclitaxel exposure causes an increase in the stem cell-like properties of prostate cancer cells.
MATERIAL AND METHODS
Paclitaxel-resistant PC-3 cells were generated from parental PC-3 cells by treating them with increasing concentrations of paclitaxel. The expression levels of the stem cell markers NANOG, C-MYC, CD44, and ABCG2 were evaluated using quantitative real-time polymerase chain reaction (RT-qPCR). A sphere formation assay was performed to test the potential of the cells to behave as stem cells, and a wound healing assay was carried out to evaluate migration ability of the cells.
RESULTS
The expression levels of C-MYC and NANOG were significantly higher in paclitaxel-resistant PC-3 cells compared to the parental PC-3 cells. However, there was no significant increase in the expression of CD44 or ABCG2. In addition, the sphere-forming capacity and migration ability of resistant PC-3 cells were increased.
CONCLUSIONS
The results of the current study indicate that paclitaxel exposure may increase the stem cell-like properties of PC-3 prostate cancer cells.
Topics: Humans; Male; Paclitaxel; Prostatic Neoplasms
PubMed: 34610216
DOI: 10.17219/acem/140590 -
Pharmaceutical Research Mar 2010Lipid nanocapsules (LNCs) are solvent-free drug nanocarriers permitting entrapment of paclitaxel and increasing its antitumoural effect in animal models after i.v....
PURPOSE
Lipid nanocapsules (LNCs) are solvent-free drug nanocarriers permitting entrapment of paclitaxel and increasing its antitumoural effect in animal models after i.v. injection. The tolerance and efficacy of LNCs after repeated dose i.v. administration were assessed in mice. The maximum tolerated dose (MTD) and 50 percent lethal dose (LD50) were studied.
METHODS
Paclitaxel-loaded LNC formulation was given i.v. at the dose of 12 mg/kg per day for 5 consecutive days in comparison with blank LNCs and saline. Histological examination, complete blood counts and biochemical quantification were performed after a recovery of 7 days. Growth of NCI-H460 subcutaneous xenografts in nude mice receiving one of the aforementioned schedules was assessed. MTD and LD50 were determined by Irwin test.
RESULTS
No mortality was observed in repeated injections studies. Histological studies revealed no lesions and no accumulation of lipids. Blood studies were normal. The tumoural growth was significantly reduced in the group treated by paclitaxel-loaded LNCs. The MTDs/LD50s of Taxol, paclitaxel-loaded LNCs and blank LNCs were 12/19.5, 96/216 and above 288/288 mg/kg, respectively.
CONCLUSIONS
This study demonstrates that a five-day i.v. injection schedule of paclitaxel-loaded LNC dispersions induces no histological or biochemical abnormalities in mice and improves paclitaxel efficacy and therapeutic index in comparison with Taxol.
Topics: Animals; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Female; Humans; Lipids; Male; Mice; Mice, Nude; Nanocapsules; Paclitaxel
PubMed: 20054705
DOI: 10.1007/s11095-009-0024-y -
Brazilian Journal of Biology = Revista... 2023Paclitaxel (PTX) is a potent anticancer drug. In the present study, PTX was loaded in poly-3-hydroxybutyrate-co-3-hydroxyvalarate (PHBV) to fabricate the PTX/PHBV...
Paclitaxel (PTX) is a potent anticancer drug. In the present study, PTX was loaded in poly-3-hydroxybutyrate-co-3-hydroxyvalarate (PHBV) to fabricate the PTX/PHBV (drug-loaded) nanoparticles via the nanoprecipitation method. Blank PHBV nanoparticles were also prepared. The drug-encapsulation efficiency of PTX/PHBV nanoparticles was 45±0.4%. The PTX/PHBV nanoparticles exhibited a pH-sensitive release profile and followed a quasi-Fickian diffusion mechanism. Cytotoxic properties of PHBV and PTX/PHBV nanoparticles were checked against the MCF-7 and Caco-2 cell lines. The PHBV nanoparticle did not inhibit the proliferation of MCF-7 and Caco-2 cell lines, thus depicting their non-toxic and biocompatible nature. On the other hand, the PTX/PHBV nanoparticles demonstrated 1.03-fold higher cytotoxicity and 1.61-fold enhanced apoptosis after treatment with the PTX/PHBV nanoparticles versus free PTX. In summary, the PHBV nanoparticles could be a potential candidate for the delivery of PTX for cancer treatment.
Topics: Humans; Paclitaxel; Caco-2 Cells; Antineoplastic Agents; Polyesters; Nanoparticles; Cell Line, Tumor
PubMed: 37970904
DOI: 10.1590/1519-6984.275688 -
European Journal of Pharmacology Apr 2022To explore inhibitory effect of iron oxide nanoparticles loaded with paclitaxel (IONP@PTX) on glioblastoma (GBM) and its potential mechanism.
OBJECTIVE
To explore inhibitory effect of iron oxide nanoparticles loaded with paclitaxel (IONP@PTX) on glioblastoma (GBM) and its potential mechanism.
METHODS
IONP@PTX was synthesized and the characteristics were assessed by chemico-physical analysis and observed directly under transmission electron microscope. U251 cells and HMC3 cells were separately incubated with IONP@PTX and PTX, and then cell viability was detected by Cell Counting Kit-8. The capacity of cell invasive and migration was verified by Scratch wound healing and Transwell migration and invasion assays. Expressions levels of autophagy and ferroptosis biomarkers were demonstrated by Western blotting assay. Intracellular reactive oxygen species (ROS) and lipid peroxidation were detected with DCFH-DA and C11-BODIPY staining, respectively. Intracellular concentration of iron ions was quantified spectrophotometrically. Moreover, inhibitory effect of IONP@PTX on GBM was evaluated by monitoring tumor growth and the toxicity of IONP@PTX was evaluated by measuring the body weight and index of liver and spleen in the mice bearing GBM xenograft.
RESULTS
The successfully synthesized IONP@PTX possesses a hydrate diameter about 36 nm and a core diameter around 10 nm. IONP@PTX exerted an inhibitory effect on U251 cells, but had little effect on HMC3 cells compared with PTX alone. In addition, IONP@PTX inhibited the capacity of cell migration and invasion, increased the levels of iron ions, ROS and lipid peroxidation, enhanced the expression of autophagy-related protein Beclin1 and LC3II, and suppressed the expression of p62 and ferroptosis-related protein GPX4 in vitro compared with control group. Moreover, administration of IONP@PTX suppressed tumor volume of GBM xenografts and decreased the expression level of GPX4 protein in tumor tissues in comparison with control group (All P < 0.05). Intriguingly, the effect of IONP@PTX on GBM could be weakened by additional 3-MA or enhanced by additional rapamycin in vitro and in vivo (P < 0.05). More importantly, IONP@PTX had no obvious toxic effect on mice bearing GBM xenograft.
CONCLUSION
IONP@PTX inhibits GBM growth by enhancing autophagy-dependent ferroptosis pathway, thus it might become a potential ferroptosis-inducing agent for ferroptosis-based tumor therapy.
Topics: Animals; Autophagy; Cell Line, Tumor; Ferroptosis; Glioblastoma; Humans; Magnetic Iron Oxide Nanoparticles; Mice; Nanoparticles; Paclitaxel
PubMed: 35278406
DOI: 10.1016/j.ejphar.2022.174860 -
International Journal of Nanomedicine 2024Most solid tumors are not diagnosed and treated until the advanced stage, in which tumors have shaped mature self-protective power, leading to off-target drugs and...
BACKGROUND
Most solid tumors are not diagnosed and treated until the advanced stage, in which tumors have shaped mature self-protective power, leading to off-target drugs and nanomedicines. In the present studies, we established a more realistic large tumor model to test the antitumor activity of a multifunctional ginsenoside Rh2-based liposome system (Rh2-lipo) on advanced breast cancer.
METHODS
Both cholesterol and PEG were substituted by Rh2 to prepare the Rh2-lipo using ethanol-water system and characterized. The effects of Rh2-lipo on cell uptake, penetration of the tumor spheroid, cytotoxicity assay was investigated with 4T1 breast cancer cells and L929 fibroblast cells. The 4T1 orthotopic-bearing large tumor model was established to study the targeting effect of Rh2-lipo and inhibitory effect of paclitaxel loaded Rh2-lipo (PTX-Rh2-lipo) on advanced breast tumors.
RESULTS
Rh2-lipo exhibit many advantages that address the limitations of current liposome formulations against large tumors, such as enhanced uptake in TAFs and tumor cells, high targeting and penetration capacity, cytotoxicity against TAFs, normalization of the vessel network, and depletion of stromal collagen. In in vivo study, PTX-Rh2-lipo effectively inhibiting the growth of advanced breast tumors and outperformed most reported PTX formulations, including Lipusu and Abraxane.
CONCLUSION
Rh2-lipo have improved drug delivery efficiency and antitumor efficacy in advanced breast cancer, which offers a novel promising platform for advanced tumor therapy.
Topics: Humans; Female; Liposomes; Breast Neoplasms; Drug Delivery Systems; Paclitaxel; Cell Line, Tumor; Ginsenosides
PubMed: 38525007
DOI: 10.2147/IJN.S437733 -
Communications Biology Sep 2023Taxol is a small molecule effector that allosterically locks tubulin into the microtubule lattice. We show here that taxol has different effects on different...
Taxol is a small molecule effector that allosterically locks tubulin into the microtubule lattice. We show here that taxol has different effects on different single-isotype microtubule lattices. Using in vitro reconstitution, we demonstrate that single-isotype α1β4 GDP-tubulin lattices are stabilised and expanded by 10 µM taxol, as reported by accelerated microtubule gliding in kinesin motility assays, whereas single-isotype α1β3 GDP-tubulin lattices are stabilised but not expanded. This isotype-specific action of taxol drives gliding of segmented-isotype GDP-taxol microtubules along convoluted, sinusoidal paths, because their expanded α1β4 segments try to glide faster than their compacted α1β3 segments. In GMPCPP, single-isotype α1β3 and α1β4 lattices both show accelerated gliding, indicating that both can in principle be driven to expand. We therefore propose that taxol-induced lattice expansion requires a higher taxol occupancy than taxol-induced stabilisation, and that higher taxol occupancies are accessible to α1β4 but not α1β3 single-isotype lattices.
Topics: Tubulin; Paclitaxel; Microtubules; Kinesins
PubMed: 37717119
DOI: 10.1038/s42003-023-05306-y