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ACS Nano Sep 2023Paclitaxel (PTX)-based chemotherapy remains the main approach to treating lung cancer but systemic toxicity limits its use. As chimeric antigen receptor-T (CAR-T)...
Paclitaxel (PTX)-based chemotherapy remains the main approach to treating lung cancer but systemic toxicity limits its use. As chimeric antigen receptor-T (CAR-T) cell-derived exosomes contain tumor-targeted CARs and cytotoxic granules (granzyme B and perforin), they are considered potential delivery vehicles for PTX. However, the low drug-loading capacity and hepatotropic properties of exosomes are obstacles to their application to extrahepatic cancer. Here, a hybrid nanovesicle named Lip-CExo@PTX was designed for immunochemotherapy of lung cancer by fusing exosomes derived from bispecific CAR-T cells targeting both mesothelin (MSLN) and programmed death ligand-1 (PD-L1) with lung-targeted liposomes. Due to the lung-targeting ability of the liposomes, over 95% of intravenously administered Lip-CExo@PTX accumulated in lung tissue. In addition, with the help of the anti-MSLN single-chain variable fragment (scFv), the PTX and cytotoxic granules inside Lip-CExo@PTX were further delivered into MSLN-positive tumors. Notably, the anti-PD-L1 scFv on Lip-CExo@PTX blocked PD-L1 on the tumors to avoid T cell exhaustion and promoted PTX-induced immunogenic cell death. Furthermore, Lip-CExo@PTX prolonged the survival time of tumor-bearing mice in a CT-26 metastatic lung cancer model. Therefore, Lip-CExo@PTX may deliver PTX to tumor cells through sequential targeted delivery and enhance the antitumor effects, providing a promising strategy for immunochemotherapy of lung cancer.
Topics: Animals; Mice; Receptors, Chimeric Antigen; Liposomes; Exosomes; T-Lymphocytes; Lung Neoplasms; Paclitaxel
PubMed: 37624742
DOI: 10.1021/acsnano.3c03456 -
Materials Science & Engineering. C,... Aug 2018In this study, we have developed an antibody fragment (AF)-conjugated gemcitabine (GEM) and paclitaxel (PTX)-loaded liposome (AF-GPL) to enhance the therapeutic efficacy...
In this study, we have developed an antibody fragment (AF)-conjugated gemcitabine (GEM) and paclitaxel (PTX)-loaded liposome (AF-GPL) to enhance the therapeutic efficacy in pancreatic cancer treatment. The maleimide-thiol chemistry was utilized to conjugate AF on the liposome surface. The dual-drug loaded liposome was nanosized and exhibited a controlled release of both the drugs. Importantly, two drugs have different release pattern over a period of time. The AF-conjugated liposome showed enhanced cellular uptake in pancreatic cancer cells compared to that of non-targeted liposome. Two-fold higher internalization of particles might increase the intracellular concentration of anticancer drugs that might further increase the therapeutic efficacy in pancreatic cancer cells. AF-GPL showed significantly higher cytotoxic effect in pancreatic cancer cell compared to that of non-targeted GPL. The IC50 value of GEM, PTX, GPL and AF-GPL were 5.9 μg/ml, 4.2 μg/ml, 1.92 μg/ml, and 0.45 μg/ml, respectively. Consistently, AF-GPL (4.12) showed significantly higher ratio of Bax/Bcl-2 compared to that of non-targeted GPL (2.8). Importantly, AF-GPL induced a significant apoptosis of cancer cells with predominant amount of cells in late apoptosis cells. Overall, AF-conjugated nanosystem could potentially improve the therapeutic efficacy in pancreatic cancers.
Topics: Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Deoxycytidine; Drug Liberation; Humans; Immunoglobulin Fragments; Liposomes; Microscopy, Confocal; Microscopy, Electron, Transmission; Paclitaxel; Pancreatic Neoplasms; Particle Size; Proto-Oncogene Proteins c-bcl-2; bcl-2-Associated X Protein; Gemcitabine
PubMed: 29752104
DOI: 10.1016/j.msec.2018.04.011 -
Zhonghua Zhong Liu Za Zhi [Chinese... Jan 2023To explore the application and efficacy of paclitaxel liposome in the treatment of advanced breast cancer among Chinese population in the real world. The clinical...
To explore the application and efficacy of paclitaxel liposome in the treatment of advanced breast cancer among Chinese population in the real world. The clinical characteristics of patients with advanced breast cancer who received paclitaxel liposome as salvage treatment from January 1, 2016 to August 31, 2019 in 11 hospitals were collected and retrospectively analyzed. The primary outcome was progression free survival (PFS), and the secondary outcome included objective response rate (ORR) and safety. The survival curve was drawn by Kaplan-Meier analysis and the Cox regression model were used for the multivariate analysis. Among 647 patients with advanced breast cancer who received paclitaxel liposome, the first-line treatment accounted for 43.3% (280/647), the second-line treatment accounted for 27.7% (179/647), and the third-line and above treatment accounted for 29.1% (188/647). The median dose of first-line and second-line treatment was 260 mg per cycle, and 240 mg in third line and above treatment. The median period of paclitaxel liposome alone and combined chemotherapy or targeted therapy is 4 cycles and 6 cycles, respectively. In the whole group, 167 patients (25.8%) were treated with paclitaxel liposome combined with capecitabine±trastuzumab (TX±H), 123 patients (19.0%) were treated with paclitaxel liposome alone (T), and 119 patients (18.4%) were treated with paclitaxel liposome combined with platinum ± trastuzumab (TP±H), 108 patients (16.7%) were treated with paclitaxel liposome combined with trastuzumab ± pertuzumab (TH±P). The median PFS of first-line and second-line patients (5.5 and 5.5 months, respectively) were longer than that of patients treated with third line and above (4.9 months, <0.05); The ORR of the first line, second line, third line and above patients were 46.7%, 36.8% and 28.2%, respectively. Multivariate analysis showed that event-free survival (EFS) and the number of treatment lines were independent prognostic factors for PFS. The common adverse events were myelosuppression, gastrointestinal reactions, hand foot syndrome and abnormal liver function. Paclitaxel liposomes is widely used and has promising efficacy in multi-subtype advanced breast cancer.
Topics: Humans; Female; Breast Neoplasms; Paclitaxel; Liposomes; Retrospective Studies; Treatment Outcome; Trastuzumab; Capecitabine; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36709125
DOI: 10.3760/cma.j.cn112152-20220129-00069 -
Asian Pacific Journal of Cancer... 2013To compare the efficacy and safety of paclitaxel liposome (Lipusu®) with paclitaxel in combination with tegafur and oxaliplatin in treating patients with advanced... (Comparative Study)
Comparative Study
AIM
To compare the efficacy and safety of paclitaxel liposome (Lipusu®) with paclitaxel in combination with tegafur and oxaliplatin in treating patients with advanced gastric cancer.
MATERIALS AND METHODS
Patients with advanced gastric cancer receiving chemotherapy were retrospectively collected, and divided into two groups. Patients in group A received paclitaxel liposomes at a dose of 135 mg/m2 on day 1 of each cycle, and patients in group B were given paclitaxel at the same dose with the same timing. All patients received tegafur at a dose of 500 mg mg/m2 on days 1-5, and oxaliplatin at a dose of 80-100 mg/m2 on day 1 for 2 cycles (each cycle was 21 d in total).
RESULTS
Fifty-eight patients could be evaluated for efficacy. The overall response rate was 47% in group A (14/30), and 46% in group B (13/28). Disease control rate was 73% in group A (22/30), and 71% in group B (20/28) (P>0.05). No significant differences were detected in hematologic and neurologic toxicities between the two groups (P>0.05). However, nausea, vomiting and hypersensitive reactions were significantly lower in group A than in group B (P<0.05).
CONCLUSION
Paclitaxel liposomes are as effective as paclitaxel when combined with tegafur and oxaliplation in treating patients with advanced gastric cancer, but adverse reactions with paclitaxel liposomes are less common.
Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Female; Fluorouracil; Follow-Up Studies; Humans; Liposomes; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Paclitaxel; Prognosis; Retrospective Studies; Stomach Neoplasms; Tegafur
PubMed: 23725180
DOI: 10.7314/apjcp.2013.14.4.2591 -
Cancer Treatment Reviews Mar 1997Paclitaxel, a novel antitumour agent, is active clinically against advanced ovarian and breast cancer and under investigation for various other cancers. One of the... (Review)
Review
Paclitaxel, a novel antitumour agent, is active clinically against advanced ovarian and breast cancer and under investigation for various other cancers. One of the problems associated with the intravenous administration of paclitaxel is its low solubility in water. The current pharmaceutical formulation consists of a 1:1 (v/v) mixture of ethanol and Cremophor EL. This formulation, however, has been demonstrated to cause some severe hypersensitivity reactions. Therefore the development of a safer intravenous formulation devoid of Cremophor EL is an important investigational issue. This review deals with some of the most promising formulation alternatives.
Topics: Antineoplastic Agents, Phytogenic; Chemistry, Pharmaceutical; Drug Carriers; Emulsions; Glycerol; Humans; Infusions, Intravenous; Liposomes; Paclitaxel; Prodrugs; Solvents
PubMed: 9225960
DOI: 10.1016/s0305-7372(97)90022-0 -
Journal of Liposome Research Mar 2019This study aimed to develop novel temperature-sensitive liposomes loading paclitaxel (PTX-TSL) and evaluate them in vitro to improve the delivery efficiency and...
This study aimed to develop novel temperature-sensitive liposomes loading paclitaxel (PTX-TSL) and evaluate them in vitro to improve the delivery efficiency and targeting of PTX. K237 peptide was conjugated to the terminal NHS of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[hydroxyl succinimidyl (polyethylene glycol)-(DSPE-PEG-NHS), and K237-modified PTX-TSL (K237-PTX-TSL) was prepared using a film dispersion method. K237-TSL encapsulation with calcein was synthesized and used to determine the cellular uptake of TSL. The morphology of K237-PTX-TSL was observed using a transmission electron microscope. The particle size and potential were measured using a laser particle size analyzer. The phase transition temperature was detected using the differential scanning calorimetry. The Cell Counting Kit-8 assay and flow cytometry were used to evaluate the effects of K237-PTX-TSL on the proliferation and cell cycle of cell lines SKOV-3 and human umbilical vein endothelial cell (HUVEC). The encapsulation efficiency of K237-PTX-TSL was 94.23% ± 0.76%. The particle diameter was 88.3 ± 4.7 nm. K237-PTX-TSL showed a fast release profile at 42 °C, while it was stable at 37 °C. PTX-TSL combined with hyperthermia significantly inhibited the cell proliferation of SKOV-3 cells and HUVECs due to increased cell arrest in the G2/M phase. The half-minimal inhibitory concentration value of K237-PTX-TSL on SKOV-3 cells and HUVECs was 13.61 ± 1.81 and 5.54 ± 0.95 nmol/L, respectively, which were significantly lower than those with PTX-TSL (p < 0.01). K237 modification could increase the targeting efficiency of TSL to cancer cells and vascular endothelial cells, thus resulting in higher cytotoxicities compared with PTX-TSL, which might be a potential formulation for targeting cancer therapy.
Topics: Animals; Antineoplastic Agents, Phytogenic; Cell Line; Humans; Liposomes; Oligopeptides; Paclitaxel; Phosphatidylethanolamines; Polyethylene Glycols; Transition Temperature
PubMed: 29671386
DOI: 10.1080/08982104.2018.1458863 -
Cancer Chemotherapy and Pharmacology Sep 2018The aim of this study was to evaluate the efficacy and toxicities of liposome-paclitaxel and carboplatin concurrent with radiotherapy for locally advanced lung squamous...
OBJECTIVE
The aim of this study was to evaluate the efficacy and toxicities of liposome-paclitaxel and carboplatin concurrent with radiotherapy for locally advanced lung squamous cell carcinoma (LSCC).
METHODS
The clinical data of 38 patients with locally advanced LSCC treated with liposome-paclitaxel based concurrent chemoradiotherapy were collected and reviewed. The overall response, toxicities, progression-free survival and overall survival were analyzed with SPSS software.
RESULT
The efficacy of treatment was classified as complete remission in 4 cases (10.5%), partial remission in 22 cases (57.9%) and stable disease in 12 cases (31.6%). The objective response rate was 68.4% (26/38). The most common types of hematological toxicities were anemia (65.7%) and leukopenia (57.9%), but all the events were transient. No paclitaxel-induced allergic reactions occurred during the treatment. The median PFS and OS time were 17.0 and 29.0 months.
CONCLUSIONS
Liposome-paclitaxel and carboplatin concurrent with radiotherapy showed a significant antitumor effect to LSCC with manageable toxicities. Further clinical investigation are warranted to evaluate the efficacy of this regimen.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Chemoradiotherapy; Female; Humans; Liposomes; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Paclitaxel; Prognosis; Progression-Free Survival; Radiotherapy, Intensity-Modulated
PubMed: 29987370
DOI: 10.1007/s00280-018-3640-6 -
Teratology Nov 1997Paclitaxel is an anticancer drug that has demonstrated severe embryotoxicity in chicks. This embryotoxicity is reduced by liposome encapsulation of the drug. The current...
Paclitaxel is an anticancer drug that has demonstrated severe embryotoxicity in chicks. This embryotoxicity is reduced by liposome encapsulation of the drug. The current study was designed to evaluate the potential of liposome encapsulation for reducing paclitaxel embryotoxicity in rats. Wistar rats were treated with paclitaxel on day 8 of pregnancy (plug = day 0) at doses of 0.67, 2.0, or 10.0 mg/kg intravenously. The same doses of paclitaxel encapsulated in liposomes were administered intravenously to other groups of animals. Control animals were given blank liposomes. Free paclitaxel produced maternal and embryotoxicity at 10.0 mg/kg with three of seven dams dying and resorption of all embryos in surviving dams. Liposome encapsulation at 10.0 mg/kg was not associated with maternal death and there were live fetuses on evaluation at term, although litter size was reduced and malformations occurred in surviving fetuses. At 2.0 mg/kg free paclitaxel, fetal weight was decreased and resorptions increased. Liposome encapsulation at 2.0 mg/kg produced litter results similar to those obtained in control animals given empty liposomes. Malformations were prominent at 2.0 mg/kg free paclitaxel and at 10.0 mg/kg paclitaxel in liposomes and included exencephaly/anencephaly, ventral wall defects, facial clefts, anophthalmia, diaphragmatic hernia, and defects of the kidney, cardiovascular system, and tail. Liposome encapsulation appeared to shift the developmental response to paclitaxel such that 10 mg/kg encapsulated drug produced effects similar to 2.0 mg/kg free drug. These results may have implications for drug delivery of therapeutic agents used during human pregnancy.
Topics: Abnormalities, Drug-Induced; Animals; Antineoplastic Agents, Phytogenic; Drug Carriers; Drug Evaluation, Preclinical; Embryonic and Fetal Development; Female; Liposomes; Paclitaxel; Pregnancy; Rats; Rats, Wistar
PubMed: 9451754
DOI: 10.1002/(SICI)1096-9926(199711)56:5<305::AID-TERA3>3.0.CO;2-W -
Zhonghua Fu Chan Ke Za Zhi Sep 2019To investigate the efficacy and side effect of paclitaxel liposome for neoadjuvant chemotherapy (NACT) in locally advanced cervical cancer. This study were included...
To investigate the efficacy and side effect of paclitaxel liposome for neoadjuvant chemotherapy (NACT) in locally advanced cervical cancer. This study were included 265 cervical cancer patients staging Ⅰb2 and Ⅱa2 who underwent paclitaxel-platinum NACT followed by radical surgery from June 2008 to December 2016 in the Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences. All patients were classified into two groups with 106 patients in paclitaxel liposome group and 159 patients in traditional paclitaxel group. The difference in clinicopathologic characteristics, efficacy and side effect were analyzed retrospectively between the two groups. (1) Clinicopathologic characteristics: there were no significant difference in clinicopathologic characteristics between the two groups, including age, body mass index, clinical stage, pathological histology, cycles of NACT, combined platinum regimen, lymph-vascular space invasion, lymph node metastasis, deep stromal invasion, and postoperative adjuvant therapy (all >0.05). (2) Efficacy: after NACT, the overall response occurred in 90 (15 complete response plus 75 partial response) of 106 cases in the paclitaxel liposome group versus 131 (21 complete response plus 110 partial response) of 159 cases in the traditional paclitaxel group without statistical significance (84.9% vs 82.4%; χ(2)=0.291, =0.590). A total of 248 patients received surgery after NACT and were evaluable in survival. The 5-year recurrence-free survival (RFS) rate and 5-year overall survival (OS) rate of these patients was 85.1% and 88.2%. The 5-year RFS rate in the paclitaxel liposome group was 85.9% compared with 85.2% in the traditional paclitaxel group, while the corresponding 5-year OS rate was 88.5% and 88.7%, respectively. There was no statistically significant difference in efficacy between the two groups (=0.968, =0.797). (3) Side effect: the incidence of allergic reaction between the paclitaxel liposome group and the traditional paclitaxel group was 0 versus 1.9% (3/159) without statistical significance (=0.277). But the incidence of neurotoxicity in the paclitaxel liposome group significantly decreased compared with the traditional paclitaxel group (6.6% vs 15.7%, <0.05), as well as the incidence of alopecia (67.9% vs 79.2%, <0.05) and myalgia (17.9% vs 28.9%, <0.05). However, significant differences were not found in terms of hematological toxicity, gastrointestinal reaction, and hepatic function damage (>0.05). In paclitaxel-platinum NACT of local advanced cervical cancer, paclitaxel liposome can achieve similar efficacy compared with traditional paclitaxel, but paclitaxel liposome is helpful in decreasing the toxicity of neurotoxicity, alopecia and myalgia.
Topics: Antineoplastic Agents, Phytogenic; Chemotherapy, Adjuvant; Female; Humans; Liposomes; Neoadjuvant Therapy; Neoplasm Staging; Paclitaxel; Retrospective Studies; Treatment Outcome; Uterine Cervical Neoplasms
PubMed: 31550774
DOI: 10.3760/cma.j.issn.0529-567x.2019.09.003 -
Journal of Biomedical Nanotechnology Jun 2019Cancer cells can develop in several ways to escape from death induced by chemotherapeutic agents, thereby weakening the anti-tumor efficacy of single-target...
Cancer cells can develop in several ways to escape from death induced by chemotherapeutic agents, thereby weakening the anti-tumor efficacy of single-target chemotherapy. Therefore, the efficacy of conventional chemotherapy hits a single target in tumor cells subject to strict limits. In this article, an AS1411 aptamer-functionalized liposome is prepared, which can simultaneously deliver paclitaxel (PTX) and siRNA into MCF-7 cells and . The simultaneous delivery of PTX and siRNA synergistically increased the number of apoptotic cells and reduced angiogenesis. This delivery method exhibited significant advantages over combined delivery of PTX and siRNA separately by different liposomal drug delivery systems. Therefore, the simultaneous delivery of PTX and PLK1-targeted siRNA using AS1411 aptamer-functionalized liposome may have good potential clinical value for the therapy of breast cancer. Nanomedicine based on simultaneous delivery of chemotherapy drugs and siRNA gene provides an effective platform for improving tumor treatment methods.
Topics: Breast Neoplasms; Cell Line, Tumor; Drug Delivery Systems; Humans; Liposomes; Paclitaxel; RNA, Small Interfering
PubMed: 31072423
DOI: 10.1166/jbn.2019.2751