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BMC Cancer Jan 2024Paclitaxel liposome (Lipusu) is known to be effective in non-small cell lung cancer (NSCLC) as first-line treatment. This study aimed to evaluate the effectiveness and...
BACKGROUND
Paclitaxel liposome (Lipusu) is known to be effective in non-small cell lung cancer (NSCLC) as first-line treatment. This study aimed to evaluate the effectiveness and safety of paclitaxel liposome based chemotherapy plus PD-1/PD-L1 inhibitor in patients with advanced NSCLC.
METHODS
In this multicenter, retrospective, real-world study, patients with advanced NSCLC who were administered paclitaxel liposome based chemotherapy plus PD-1/PD-L1 inhibitor in three centers (Peking University People's Hospital as the lead center) in China between 2016 and 2022 were included. Progression-free survival (PFS), overall survival (OS), objective response rate, disease control rate, and adverse events (AEs) were evaluated.
RESULTS
A total of 49 patients were included, with 33 (67.3%) receiving paclitaxel liposome based chemotherapy plus PD-1/PD-L1 inhibitor as first-line treatment. There were 34 patients (69.4%) diagnosed with squamous cell carcinoma and 15 (30.6%) with adenocarcinoma. The median follow-up was 20.5 (range: 3.1-41.1) months. The median PFS and OS of all patients were 9.7 months (95% confidence interval [CI], 7.0-12.4) and 30.5 months (95% CI, not evaluable-not evaluable), respectively. Patients with squamous cell carcinoma and adenocarcinoma had median PFS of 11 months (95%CI, 6.5-15.5) and 9.3 months (95%CI, 7.0-12.4), respectively. The median PFS was 9.9 months (95%CI, 7.1-12.7) in patients who received the combined regimen as first-line treatment. Treatment-related AEs of any grade were observed in 25 (51.0%) patients, and AEs of grade 3 or worse were observed in nine patients (18.4%). The most common treatment-related AEs were myelosuppression (14.3%) and fever (10.2%).
CONCLUSIONS
Paclitaxel liposome based chemotherapy plus PD-1/PD-L1 inhibitor prolonged the PFS in advanced NSCLC with acceptable safety, which was worthy of clinical application.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Paclitaxel; Lung Neoplasms; Liposomes; Immune Checkpoint Inhibitors; Programmed Cell Death 1 Receptor; Retrospective Studies; Immunotherapy; Antineoplastic Combined Chemotherapy Protocols; Adenocarcinoma; Carcinoma, Squamous Cell
PubMed: 38238648
DOI: 10.1186/s12885-024-11860-3 -
RSC Advances Oct 2019With the advantages and development of MRI nano-contrast agents (CAs), increasing number of MRI-based theranostic nanoparticles have emerged. Liposome, as a biosafe...
With the advantages and development of MRI nano-contrast agents (CAs), increasing number of MRI-based theranostic nanoparticles have emerged. Liposome, as a biosafe nanocarrier has been used phase III trial for cancer treatment. In this study, liposome was employed as a nanocarrier to co-encapsulate MRI nano-contrast agent poly(ethylene glycol)-grafted manganese oxide (PEG-MnO) and anticancer drug paclitaxel (PTX) for the fabrication of a novel theranostic nanocomplex. After being further modified with AS1411 aptamer, the obtained nanoprobe AS1411-liposome-PEG-MnO-PTX displayed the potential of simultaneous MRI diagnosis and therapy of renal carcinoma and . It was found that compared with PEG-MnO nano-CA, liposome-PEG-MnO and AS1411-liposome-PEG-MnO presented a stronger MR contrast enhancement effect in the tumor and longer retention time in the tumor region. More importantly, the introduction of AS1411 aptamer further enhanced the MRI effect and the tumor growth inhibition effect, showing its potential use as a theranostic nanoprobe for renal carcinoma.
PubMed: 35530716
DOI: 10.1039/c9ra06878c -
Lutein-Based pH and Photo Dual-Responsive Novel Liposomes Coated with Ce6 and PTX for Tumor Therapy.ACS Omega Aug 2023Liposomes are considered the best nanocarrier for delivering cancer drugs such as chlorin e6 (Ce6) and paclitaxel (PTX). However, the poor stability and non-selectivity...
Liposomes are considered the best nanocarrier for delivering cancer drugs such as chlorin e6 (Ce6) and paclitaxel (PTX). However, the poor stability and non-selectivity release of liposomes may severely limit their further applications. In this study, based on the characteristics of lutein (L) photo-response and orthoester (OE) acid-response, stable and dual-responsive liposomes (Dr-lips) have been prepared. The Dr-lips exhibited a spherical shape with a uniform size of approximately 58.27 nm. Moreover, they displayed a zeta potential ranging from -45.45 to -28.25 mV and showed excellent storage stability, indicating stable colloidal properties. Additionally, they achieved high drug encapsulation rates, with 92.27% for PTX and 90.34% for Ce6, respectively. Meanwhile, under near-infrared (NIR) light at 660 nm, Ce6 plays a key role in accelerating the photodegradation rate of lutein and PEG-OE-L while also enhancing tissue penetration ability. Additionally, Dr-lips loaded with Ce6 and PTX not only displayed excellent pH and photo dual-responsiveness for targeted delivering and releasing but also showed remarkable reactive oxygen species (ROS) generation capacity and impressive anti-tumor activity in vitro. Therefore, it provides a novel strategy for optimizing stability and enhancing their targeted drug delivery of liposome.
PubMed: 37663483
DOI: 10.1021/acsomega.3c04228 -
Cancer Medicine Dec 2021Many real-world studies of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) are restricted to single centers, limiting the generalizability of their...
BACKGROUND
Many real-world studies of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) are restricted to single centers, limiting the generalizability of their insights. This study aimed to identify important population-based predictors for survival in patients diagnosed with mPDAC in a broader setting.
METHODS
Data between 1 January 2017 and 31 December 2019 were extracted from the Flatiron Health EHR database. Treatment-specific predictive models were generated for patients treated with first-line gemcitabine+nab-paclitaxel (GNP), FOLFIRINOX, gemcitabine monotherapy (gem-mono), and second-line liposomal irinotecan-based regimens. The holdout method was used for cross-validation. Age at diagnosis, sex, BMI, smoking status, and ECOG performance score were included in all models with additional demographic, clinical characteristics, and hematological function assessed for inclusion.
RESULTS
Of the 3625 patients, 43% received GNP, 26% received FOLFIRINOX, 7% received gem-mono, and 23% received other regimens; 40% (n = 1448) advanced to the second line. Among all first-line patients, the following were included in the final model: prior surgery, white blood cell (WBC) counts, serum albumin (SA), liver function tests (LFTs), serum bilirubin, serum carbohydrate antigen 19-9, and ascites. Models for patients receiving specific therapies differed from the overall model, GNP (ascites removed), FOLFIRINOX (stage at initial diagnosis added), and gem-mono (LFTs omitted). Alkaline phosphatase (ALP), SA, and WBC counts were important predictors of survival among patients treated with second-line liposomal irinotecan. Across all regimens, the strongest predictors of survival were ECOG score, SA, and ALP.
CONCLUSIONS
In this real-world study of patients with mPDAC, important population prognostic factors of survival were identified in a large cohort of patients receiving systemic treatment.
Topics: Adenocarcinoma; Aged; Aged, 80 and over; Carcinoma, Pancreatic Ductal; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Prognosis; Retrospective Studies; Survival Analysis
PubMed: 34811961
DOI: 10.1002/cam4.4415 -
Gland Surgery Dec 2021The anti-tumor activity of pyrotinib has been confirmed in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. This study investigated the...
BACKGROUND
The anti-tumor activity of pyrotinib has been confirmed in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. This study investigated the effect of pyrotinib plus nab-paclitaxel, doxorubicin, and cyclophosphamide as neoadjuvant therapy in patients with HER2-positive locally advanced breast cancer.
METHODS
In this single-center retrospective study, female patients with HER2-positive locally advanced breast cancer received pyrotinib 320 mg orally once a day and the TAC regimen (nab-paclitaxel 260 mg/m, liposomal doxorubicin 20 mg/m, and cyclophosphamide 600 mg/m) on day 1 of each 21-day cycle. Surgery was performed after 4-6 cycles of neoadjuvant therapy. The outcomes included total pathological complete response (tpCR, ypT0/Tis ypN0) rate, objective response rate (ORR) after neoadjuvant therapy, progression-free survival, overall survival, and the incidence of adverse events (AEs).
RESULTS
Between March 2019 and January 2020, a total of 22 patients were included. The median age was 48 years (range, 32-60). The ORR was 100% after the completion of neoadjuvant therapy. Ten (45.5%) patients achieved tpCR, including four of ten (40.0%) patients with positive hormone receptor, and six of 12 (50.0%) patients with negative hormone receptor. As at December 2020, no disease recurrence, progression, or death occurred. All patients suffered AEs after neoadjuvant therapy, most of which were grade 1-2. Grade ≥3 AEs included diarrhea [4 (18.2%)], rash [2 (9.1%)], and hand-foot syndrome [1 (4.5%)].
CONCLUSIONS
Neoadjuvant pyrotinib combined with the TAC regimen showed promising clinical benefit in patients with HER2-positive locally advanced breast cancer, with an acceptable safety profile.
PubMed: 35070896
DOI: 10.21037/gs-21-770 -
Pharmaceutics Jan 2024Breast cancer (BC) has become the fifth most prevalent cause of cancer-related morbidity, attracting significant attention from researchers due to its heightened... (Review)
Review
Breast cancer (BC) has become the fifth most prevalent cause of cancer-related morbidity, attracting significant attention from researchers due to its heightened malignancy and drug resistance. Conventional chemotherapy approaches have proven inadequate in addressing all BC subtypes, highlighting the urgent need for novel therapeutic approaches or drugs. Curcumin (CUR), a phytochemical derived from Curcuma longa (turmeric), has shown substantial potential in inhibiting BC cell migration, metastasis, and proliferation. However, the use of CUR in this context comes with challenges due to its dynamic and easily degradable nature, poor aqueous solubility, low bioavailability, rapid metabolism, and swift systemic elimination, collectively limiting its clinical applications. As such, we provide an overview of the properties, synthesis, and characterization of the hybridization of CUR and its analogue with chemo-drug building blocks. We reviewed research from the last five years on CUR's biogenesis with respect to the regulation of BC, revealing that CUR participates in arresting BC cells in the cell cycle and significantly induces apoptosis in BC cells. Information on the chemotherapeutic and antitumor mechanisms of CUR in BC, including regulation of the cell cycle, increased cell apoptosis, and inhibition of multidrug resistance (MDR), was compiled. Additionally, we provide an overview of CUR loaded into nanomaterials that are cotreated with other chemotherapeutic drugs, such as paclitaxel, thymoquinone, and tamoxifen. In this review, we discuss different types of nanoparticles that can be used for CUR delivery, such as polymeric nanoparticles, carbon nanotubes, and liposomes. By comparing the size, entrapment efficiency, drug-loading capacity, release time, biocompatibility, pharmaceutical scale, and reproducibility of various nanomaterials, we aimed to determine which formulations are better suited for loading CUR or its analogue. Ultimately, this review is expected to offer inspiring ideas, promising strategies, and potential pathways for developing advanced anti-BC strategy nanosystems in clinical practice.
PubMed: 38258090
DOI: 10.3390/pharmaceutics16010079 -
Advanced Science (Weinheim,... Sep 2021Glioblastoma (GBM) is the most malignant brain tumor with unmet therapeutic demand. The blood-brain-barrier (BBB) and tumor heterogeneity limit the treatment...
Glioblastoma (GBM) is the most malignant brain tumor with unmet therapeutic demand. The blood-brain-barrier (BBB) and tumor heterogeneity limit the treatment effectiveness of various interventions. Here, an ultrasound augmented chemo/immuno therapy for GBM using a neutrophil-delivered nanosensitizer, is developed. The sensitizer is composed of a ZnGa O :Cr (ZGO) core for persistent luminescence imaging and a hollow sono-sensitive TiO shell to generate reactive oxygen species (ROS) for controlled drug release. Immune checkpoint inhibitor (Anti-PD-1 antibody) is trapped in the interior of the porous ZGO@TiO with paclitaxel (PTX) loaded liposome encapsulation to form ZGO@TiO @ALP. Delivered by neutrophils (NEs), ZGO@TiO @ALP-NEs can penetrate through BBB for GBM accumulation. After intravenous injection, ultrasound irradiation at GBM sites initiates ROS generation from ZGO@TiO @ALP, leading to liposome destruction for PTX and anti-PD-1 antibody release to kill tumors and induce local inflammation, which in-turn attractes more ZGO@TiO @ALP-NEs to migrate into tumor sites for augmented and sustained therapy. The treatment enhances the survival rate of the GBM bearing mice from 0% to 40% and endows them with long-term immuno-surveillance for tumor recurrence, providing a new approach for precision therapy against GBM and other cancers.
Topics: Animals; Antineoplastic Agents; Brain Neoplasms; Disease Models, Animal; Drug Carriers; Drug Delivery Systems; Glioblastoma; Immune Checkpoint Inhibitors; Immunotherapy; Luminescence; Mice; Mice, Nude; Nanocapsules; Neutrophils; Titanium; Ultrasonic Therapy
PubMed: 34196474
DOI: 10.1002/advs.202004381 -
Nature Communications Feb 2024The dynamic protein corona formed on nanocarriers has been revealed to strongly affect their in vivo behaviors. Precisely manipulating the formation of protein corona on...
The dynamic protein corona formed on nanocarriers has been revealed to strongly affect their in vivo behaviors. Precisely manipulating the formation of protein corona on nanocarriers may provide an alternative impetus for specific drug delivery. Herein, we explore the role of glycosylated polyhydroxy polymer-modified nanovesicles (CP-LVs) with different amino/hydroxyl ratios in protein corona formation and evolution. CP-LVs with an amino/hydroxyl ratio of approximately 0.4 (CP-LVs) are found to efficiently suppress immunoglobulin adsorption in blood and livers, resulting in prolonged circulation. Moreover, CP-LVs adsorb abundant tumor distinctive proteins, such as CD44 and osteopontin in tumor interstitial fluids, mediating selective tumor cell internalization. The proteins corona transformation specific to the environment appears to be affected by the electrostatic interaction between CP-LVs and proteins with diverse isoelectric points. Benefiting from surface modification-mediated protein corona regulation, paclitaxel-loaded CP-LVs demonstrate superior antitumor efficacy to PEGylated liposomes. Our work offers a perspective on rational surface-design of nanocarriers to modulate the protein corona formation for efficient drug delivery.
Topics: Polymers; Protein Corona; Nanoparticles; Drug Delivery Systems; Osteopontin
PubMed: 38326312
DOI: 10.1038/s41467-024-45254-7 -
Thoracic Cancer Mar 2022This study analyzed the efficacy and safety of neoadjuvant chemotherapy with liposomal paclitaxel plus platinum in patients with locally advanced resectable esophageal...
BACKGROUND
This study analyzed the efficacy and safety of neoadjuvant chemotherapy with liposomal paclitaxel plus platinum in patients with locally advanced resectable esophageal squamous cell carcinoma (ESCC).
METHODS
The data of patients with locally advanced resectable ESCC (staging cT2N + M0, cT3-4aNanyM0, IA-IVA) who received preoperative chemotherapy with liposomal paclitaxel plus platinum (cisplatin, nedaplatin or carboplatin) in HuanXing Cancer Hospital from July 2018 to October 2019 were collected. The primary endpoint of this study was R0 resection rate, and secondary endpoints were pathological complete response (pCR) rate, 1- and 2-year overall survival (OS) rate, 1-year and 18-month disease-free survival (DFS) rate, and safety.
RESULTS
A total of 32 eligible patients were included in this study. All patients received neoadjuvant chemotherapy and surgery. The R0 resection rate was 93.8%, the pCR rate was 12.5%, and down-staging was achieved in 14 patients (47.8%). Median follow-up was 31.0 months (95% confidence interval [CI] 30.1-31.9 months). The 1- and 2-year OS rates were 96.9% and 78.1%, and the 1-year and 18-month DFS rates were 86.7% and 76.7%, respectively. The median DFS and OS were not reached. The incidence rate of neoadjuvant chemotherapy related grade 3-4 adverse events was 21.9%, including neutropenia (21.9%) and leukopenia (9.4%).
CONCLUSIONS
The results of this study suggest that liposomal paclitaxel combined with platinum as neoadjuvant chemotherapy can provide satisfactory R0 resection rate and survival rate, and significant tumor down-staging effect for patients with locally advanced resectable ESCC, with safety profile.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Epithelial Cells; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Humans; Neoadjuvant Therapy; Neoplasm Staging; Paclitaxel; Platinum; Retrospective Studies
PubMed: 35118824
DOI: 10.1111/1759-7714.14328 -
International Journal of Molecular... Jan 2023Nanoparticles are heterologous small composites that are usually between 1 and 100 nanometers in size. They are applied in many areas of medicine with one of them being... (Review)
Review
Nanoparticles are heterologous small composites that are usually between 1 and 100 nanometers in size. They are applied in many areas of medicine with one of them being drug delivery. Nanoparticles have a number of advantages as drug carriers which include reduced toxic effects, increased bioavailability, and their ability to be modified for specific tissues or cells. Due to the exciting development of nanotechnology concomitant with advances in biotechnology and medicine, the number of clinical trials devoted to nanoparticles for drug delivery is growing rapidly. Some nanoparticles, lipid-based types, in particular, played a crucial role in the developing and manufacturing of the two COVID-19 vaccines-Pfizer and Moderna-that are now being widely used. In this analysis, we provide a quantitative survey of clinical trials using nanoparticles during the period from 2002 to 2021 as well as the recent FDA-approved drugs (since 2016). A total of 486 clinical trials were identified using the clinicaltrials.gov database. The prevailing types of nanoparticles were liposomes (44%) and protein-based formulations (26%) during this period. The most commonly investigated content of the nanoparticles were paclitaxel (23%), metals (11%), doxorubicin (9%), bupivacaine and various vaccines (both were 8%). Among the FDA-approved nanoparticle drugs, polymeric (29%), liposomal (22%) and lipid-based (21%) drugs were the most common. In this analysis, we also discuss the differential development of the diverse groups of nanoparticles and their content, as well as the underlying factors behind the trends.
Topics: Humans; COVID-19 Vaccines; COVID-19; Liposomes; Nanoparticles; Lipids
PubMed: 36614230
DOI: 10.3390/ijms24010787