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International Journal of Molecular... Feb 2023Cerasomes are a promising modification of liposomes with covalent siloxane networks on the surface that provide outstanding morphological stability while maintaining all...
Cerasomes are a promising modification of liposomes with covalent siloxane networks on the surface that provide outstanding morphological stability while maintaining all the useful traits of liposomes. Herein, thin film hydration and ethanol sol injection methods were utilized to produce cerasomes of various composition, which were then evaluated for the purpose of drug delivery. The most promising nanoparticles obtained by the thin film method were studied closely using MTT assay, flow cytometry and fluorescence microscopy on T98G glioblastoma cell line and modified with surfactants to achieve stability and the ability to bypass the blood-brain barrier. An antitumor agent, paclitaxel, was loaded into cerasomes, which increased its potency and demonstrated increased ability to induce apoptosis in T98G glioblastoma cell culture. Cerasomes loaded with fluorescent dye rhodamine B demonstrated significantly increased fluorescence in brain slices of Wistar rats compared to free rhodamine B. Thin film hydration with Tween 80 addition was established as a more reliable and versatile method for cerasome preparation. Cerasomes increased the antitumor action of paclitaxel toward T98G cancer cells by a factor of 36 and were able to deliver rhodamine B over the blood-brain barrier in rats.
Topics: Rats; Animals; Liposomes; Glioblastoma; Rats, Wistar; Drug Delivery Systems; Paclitaxel; Lipids; Cell Line, Tumor
PubMed: 36835043
DOI: 10.3390/ijms24043632 -
International Journal of Nanomedicine 2020Certain patients with triple-negative breast cancer cannot tolerate the serious adverse effects of cytotoxic chemotherapy agents, which significantly affect the disease...
BACKGROUND
Certain patients with triple-negative breast cancer cannot tolerate the serious adverse effects of cytotoxic chemotherapy agents, which significantly affect the disease prognosis.
PURPOSE
Research into the combined use of photosensitizers and non-cytotoxic antineoplastic drugs for the safe treatment of triple-negative breast cancer is vital.
METHODS
In this study, the photosensitizer indocyanine green and the natural drug parthenolide were co-loaded into thermosensitive liposomes. Under a near-infrared irradiation, indocyanine green reached excitation levels, releasing heat, and the liposome underwent a phase transition, releasing the drug were researched.
RESULTS
Thus, indocyanine green and parthenolide exert synergistic antineoplastic effects. In the nude mice xenograft MDA-MB-231 tumor model, the tumor inhibition rate of indocyanine green-parthenolide thermosensitive liposomes was approximately 2.08-fold than that of paclitaxel and demonstrated a good initial safety evaluation.
CONCLUSION
Photosensitizers and non-cytotoxic antineoplastic agents in combination with nanoscale carriers should be further investigated for the treatment of tumors.
Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Cell Cycle Checkpoints; Cell Line, Tumor; Drug Delivery Systems; Endocytosis; Female; Humans; Hydrodynamics; Indocyanine Green; Liposomes; Mice, Inbred BALB C; Mice, Nude; Paclitaxel; Photosensitizing Agents; Reactive Oxygen Species; Sesquiterpenes; Temperature; Tissue Distribution; Treatment Outcome; Triple Negative Breast Neoplasms; Tumor Burden
PubMed: 32440118
DOI: 10.2147/IJN.S245289 -
Heliyon Feb 2023Pigment epithelium-derived factor (PEDF) is a secreted glycoprotein involved in various biological processes. Its expression declines during ovarian carcinogenesis where...
Pigment epithelium-derived factor (PEDF) is a secreted glycoprotein involved in various biological processes. Its expression declines during ovarian carcinogenesis where it could decrease macrophages polarization, inhibit angiogenesis and induce apoptosis. Altogether, PEDF represents an ideal anti-cancer agent against ovarian cancer. We previously proposed the non-viral Sleeping Beauty transposon (SBT) system to stably integrate the PEDF transgene into ovarian cancer cells. Here, we report the development of liposomes and lipid nanoparticles for SBT-PEDF gene therapy. We determined that the SBT-PEDF nanolipid delivery system was the best system to increase the expression of PEDF in ovarian cancer spheroids. We also developed an ex vivo model of ovarian tumors which allowed us to show that nanolipoplexe in combination to paclitaxel exhibits synergistic and effective anti-tumor efficacy on ovarian tumors. These findings demonstrate that lipid nanoparticle for SBT-PEDF gene therapy may be a promising therapeutic approach for ovarian cancer.
PubMed: 36873150
DOI: 10.1016/j.heliyon.2023.e13676 -
Frontiers in Oncology 2022The main objective of this systematic review was to examine the literature evaluating association of image-based body composition with chemotherapy-related toxicity in...
OBJECTIVES
The main objective of this systematic review was to examine the literature evaluating association of image-based body composition with chemotherapy-related toxicity in ovarian cancer patients. A secondary objective was to evaluate the different definitions of sarcopenia across studies.
METHODS
This systematic review was conducted according to the PRISMA-DTA statement and the protocol was registered on Prospero. A comprehensive literature search of 3 electronic databases was performed by two authors. For each eligible article, information was collected concerning the clinical setting; basic study data; population characteristics; technical aspects; body composition features; chemotherapy drugs administered; association of body composition values and toxicities. The overall quality of the included studies was critically evaluated.
RESULTS
After the initial retrieval of 812 articles, the systematic review included 6 articles (5/6 studies were retrospective; one was prospective). The number of patients ranged between 69 and 239; mean/median age ranged between 55 and 65 years; the percentage of sarcopenic patients ranged between 25% and 54%. The cut-off values to define sarcopenia and the vertebral levels for evaluation of body composition were different. Five studies included chemotherapy based on carboplatin and paclitaxel, 1 included chemotherapy based on pegylated liposomal doxorubicin. Among the studies including carboplatin and paclitaxel, 3/5 demonstrated an association with toxicity, whereas 2/5 did not. Altogether, 4/6 papers demonstrated an association between the body composition values and the development of chemotherapy-related toxicities.
CONCLUSIONS
There is a wide variability of results about the association of body composition and chemotherapy-related toxicity in ovarian cancer patients. Therefore further studies, possibly including a comprehensive assessment of body compartments and where the definition of body composition cut-offs is constant, are warranted to better understand this association.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022337753, identifier (CRD42022337753).
PubMed: 36408182
DOI: 10.3389/fonc.2022.1057631 -
Soft Matter Feb 2023Hybrid phospholipid/block copolymer membranes where polymers and lipids are molecularly mixed or phase-separated into polymer-rich and lipid-rich domains are promising...
Hybrid phospholipid/block copolymer membranes where polymers and lipids are molecularly mixed or phase-separated into polymer-rich and lipid-rich domains are promising drug delivery materials. Harnessing the chemical diversity of polymers and the biocompatability of lipids is a compelling approach to design the next generation of drug carriers. Here, we report on the development of a microfluidics-based strategy analogous to produce lipid nanoparticles (LNPs) for the nanomanufacturing of multilayered hybrid nanoparticles (HNPs). Using X-ray scattering, Cryo-electron, and polarized microscopy we show that phosphatidylcholine (PC) and PBD--PEO (poly(butadiene--ethylene oxide)) hybrid membranes can be nanomanufactured by microfluidics into HNPs with dense and multilayered cores which are ideal carriers of low-solubility drugs of the Biopharmaceutical Classification System (BCS) II and IV such as antimalarial DSM265 and Paclitaxel, respectively.
Topics: Polymers; Solubility; Microfluidics; Nanoparticles; Liposomes; Lipids
PubMed: 36752169
DOI: 10.1039/d2sm01443b -
Life (Basel, Switzerland) Nov 2021Pancreatic cancer is the most common lethal tumor in America. This lethality is related to limited treatment options. Conventional treatments involve the non-specific... (Review)
Review
Pancreatic cancer is the most common lethal tumor in America. This lethality is related to limited treatment options. Conventional treatments involve the non-specific use of chemotherapeutical agents such as 5-FU, capecitabine, gemcitabine, paclitaxel, cisplatin, oxaliplatin, or irinotecan, which produce several side effects. This review focuses on the use of targeted nanoparticles, such as metallic nanoparticles, polymeric nanoparticles, liposomes, micelles, and carbon nanotubes as an alternative to standard treatment for pancreatic cancer. The principal objective of nanoparticles is reduction of the side effects that conventional treatments produce, mostly because of their non-specificity. Several molecular markers of pancreatic cancer cells have been studied to target nanoparticles and improve current treatment. Therefore, properly functionalized nanoparticles with specific aptamers or antibodies can be used to recognize pancreatic cancer cells. Once cancer is recognized, these nanoparticles can attack the tumor by drug delivery, gene therapy, or hyperthermia.
PubMed: 34833063
DOI: 10.3390/life11111187 -
Heliyon Oct 2023Advanced non-small cell lung cancer (NSCLC) is often complicated by leptomeningeal metastases (LMs), especially in patients carrying EGFR mutations. EGFR tyrosine kinase...
Afatinib overcoming resistance to icotinib and osimertinib in NSCLC with leptomeningeal metastasis in patients with acquired EGFR L858R/T790M or L858R/S768I mutations: Two case reports.
BACKGROUND
Advanced non-small cell lung cancer (NSCLC) is often complicated by leptomeningeal metastases (LMs), especially in patients carrying EGFR mutations. EGFR tyrosine kinase inhibitors (TKIs) are the first-line drug for patients with specific gene mutations, such as EGFR exon 19 deletion or exon 21 L858R mutation. However, after long-term TKI use, patients eventually develop drug resistance and acquire new mutations. Acquiring the EGFR T790 M mutation during TKI treatment is a marker for first/second generation TKI resistance. Osimertinib (a third-generation TKI) could overcome this resistance, especially for patients who have already developed NSCLC-LM. Treating NSCLC patients with osimertinib resistance is challenging. Our aim was to investigate whether afatinib is effective in NSCLC-LM patient who showed resistance to osimertinib. Herein, we report two patients with resistance to first- and third-generation TKIs who benefited from second-generation TKI.
CASE SUMMARY
Case one: A 43-year-old man was diagnosed with stage 3A NSCLC with EGFR exon 19 deletion. He underwent surgery and received 4 rounds of chemotherapy (oxaliplatin combined with liposomal paclitaxel), after which the disease was controlled by icotinib (a first-generation TKI) for 4 years. Then, he showed poor drug response and bone metastasis. A liquid biopsy was carried out, and the EGFR L858R/T790 M compound mutation was found. The patient was given osimertinib (a third-generation TKI). The patient was in a stable condition for 2 years and then he developed bilateral peripheral facial palsy. Brain MRI showed enhancement in the left temporal lobe and meninges, and cerebrospinal fluid (CSF) cytology detected tumour cells in the CSF. NSCLC-LM was diagnosed. His performance status (PS) score was 3-4. Liquid biopsy and next-generation sequencing were performed again. Different gene mutations and copy number alterations were found this time, including EGFR L858R, but without the EGFR T790 M mutation. His disease was controlled with intrathecal methotrexate and oral afatinib (a second generation TKI). The patient has shown clinical remission (PS score: 1-2) until now, which is longer than 10 months.
CASE TWO
A 50-year-old man was diagnosed with NSCLC in May 2020. He underwent one round of chemotherapy before thoracoscopic partial lobectomy of the right upper lung. Histological study of the lung tissue showed lung adenocarcinoma with the EGFR L858R mutation. Then, the disease was controlled with icotinib. One year later, he was diagnosed with NSCLC-LM. Liquid biopsy and sequencing showed an EGFR L858R/S768I compound mutation. The patient was treated with osimertinib. His condition was stable for 5 months before his central nervous system (CNS) symptoms were exacerbated. Liquid biopsy and sequencing were carried out again, and his gene mutation profile had not changed much. Then, the patient was given afatinib, and his condition has remained stable for 11 months.
CONCLUSION
Afatinib might be suitable for NSCLC-LM patients with EGFR compound mutations who show resistance to icotinib and osimertinib, since it might help overcome first- and third-generation TKI resistance.
PubMed: 37860534
DOI: 10.1016/j.heliyon.2023.e20690 -
Journal of Nanobiotechnology May 2021Porphyrin-lipids are versatile building blocks that enable cancer theranostics and have been applied to create several multimodal nanoparticle platforms, including...
BACKGROUND
Porphyrin-lipids are versatile building blocks that enable cancer theranostics and have been applied to create several multimodal nanoparticle platforms, including liposome-like porphysome (aqueous-core), porphyrin nanodroplet (liquefied gas-core), and ultrasmall porphyrin lipoproteins. Here, we used porphyrin-lipid to stabilize the water/oil interface to create porphyrin-lipid nanoemulsions with paclitaxel loaded in the oil core (PLNE-PTX), facilitating combination photodynamic therapy (PDT) and chemotherapy in one platform.
RESULTS
PTX (3.1 wt%) and porphyrin (18.3 wt%) were loaded efficiently into PLNE-PTX, forming spherical core-shell nanoemulsions with a diameter of 120 nm. PLNE-PTX demonstrated stability in systemic delivery, resulting in high tumor accumulation (~ 5.4 ID %/g) in KB-tumor bearing mice. PLNE-PTX combination therapy inhibited tumor growth (78%) in an additive manner, compared with monotherapy PDT (44%) or chemotherapy (46%) 16 days post-treatment. Furthermore, a fourfold reduced PTX dose (1.8 mg PTX/kg) in PLNE-PTX combination therapy platform demonstrated superior therapeutic efficacy to Taxol at a dose of 7.2 mg PTX/kg, which can reduce side effects. Moreover, the intrinsic fluorescence of PLNE-PTX enabled real-time tracking of nanoparticles to the tumor, which can help inform treatment planning.
CONCLUSION
PLNE-PTX combining PDT and chemotherapy in a single platform enables superior anti-tumor effects and holds potential to reduce side effects associated with monotherapy chemotherapy. The inherent imaging modality of PLNE-PTX enables real-time tracking and permits spatial and temporal regulation to improve cancer treatment.
Topics: Animals; Cell Line, Tumor; Drug Carriers; Drug Therapy; Emulsions; Humans; Lipids; Liposomes; Mice; Nanoparticles; Paclitaxel; Photochemotherapy; Polyethylene Glycols; Porphyrins; Therapeutic Uses; Xenograft Model Antitumor Assays
PubMed: 34034749
DOI: 10.1186/s12951-021-00898-1 -
Gels (Basel, Switzerland) Apr 2022Peritoneal dissemination is a disease that is difficult to treat surgically because it is widely scattered and proliferates in the abdominal cavity. It is a challenge...
Peritoneal dissemination is a disease that is difficult to treat surgically because it is widely scattered and proliferates in the abdominal cavity. It is a challenge that even if the drug is administered directly into the abdominal cavity, it rapidly disappears from the abdominal cavity, and the therapeutic effect is not optimal, as expected. In this study, for a liposomal paclitaxel in temperature-sensitive gel that is a suspension before administration and a gel after intraperitoneal administration, the antitumor effect of this formulation was evaluated. Temperature-sensitive gels were prepared using methylcellulose, sodium citrate, and macrogol 4000 and mixed with liposomal paclitaxel. Liposomal paclitaxel containing temperature-sensitive gel in the body was administered into the peritoneal cavity of a mouse model of peritoneal dissemination; the number of cells was significantly reduced compared to a paclitaxel solution of liposomal paclitaxel. These results showed that the liposome in temperature-sensitive gel inhibited cell proliferation in the abdominal cavity. This formulation can be administered easily at room temperature, and it gels and remains in the abdominal cavity for a long period, resulting in a more substantial effect than the existing drug.
PubMed: 35621550
DOI: 10.3390/gels8050252 -
Gynecologic Oncology May 2024The addition of bevacizumab to chemotherapy for platinum-resistant (PL-R) ovarian cancer (OC) improved progression-free (PFS) but not overall survival (OS) in clinical...
OBJECTIVES
The addition of bevacizumab to chemotherapy for platinum-resistant (PL-R) ovarian cancer (OC) improved progression-free (PFS) but not overall survival (OS) in clinical trials. We explored real-world outcomes in Ontario, Canada, and compared survival in the pre- and post-bevacizumab era.
METHODS
Administrative databases were utilized to identify all patients treated with bevacizumab for PL-R OC. Time on treatment (ToT) was used as surrogate for PFS. Median OS was determined using the Kaplan-Meier method. Factors associated with ToT/OS were identified using a Cox proportional hazard model. A before and after comparative effectiveness analysis was performed to determine mOS for patients treated pre- and post-bevacizumab approval.
RESULTS
From 2017 to 2019, 176 patients received bevacizumab. Median ToT was 3 months and OS was 11 months. Sixty-four percent received liposomal doxorubicin and 34% received paclitaxel. ToT (6 vs 3 months; HR 0.44; p < 0.0001) and OS (14 vs 9 months; HR 0.45; p = 0.0089) were longer with bevacizumab/paclitaxel. OS was not significantly different pre- and post-bevacizumab funding (8 vs 9 months; HR 1.01; 0.937). Median OS increased for those receiving paclitaxel (6 vs 11 months), but those in the post group were younger, more likely to have undergone primary surgery and had less co-morbidities.
CONCLUSION
Real-world outcomes with bevacizumab in PL-R OC are inferior to those in the pivotal clinical trial. Survival has not significantly improved since funding became publicly available, indicating a substantial efficacy-effectiveness gap between trial and real-world outcomes. Median OS and ToT were significantly better when bevacizumab was given with paclitaxel.
Topics: Humans; Bevacizumab; Female; Antineoplastic Combined Chemotherapy Protocols; Ovarian Neoplasms; Middle Aged; Aged; Drug Resistance, Neoplasm; Paclitaxel; Progression-Free Survival; Ontario; Adult; Doxorubicin; Retrospective Studies; Carcinoma, Ovarian Epithelial; Aged, 80 and over; Polyethylene Glycols
PubMed: 38281412
DOI: 10.1016/j.ygyno.2024.01.027