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Frontiers in Oncology 2023Immune checkpoint inhibitors (ICIs) have been widely applicated in clinical therapy in recent years. Skin-related adverse reaction is one of the most common adverse...
Immune checkpoint inhibitors (ICIs) have been widely applicated in clinical therapy in recent years. Skin-related adverse reaction is one of the most common adverse events for ICIs. Stevens-Johnson syndrome (SJS) is one of the serious cutaneous reactions threatening the life. Here, we reported a case of 76-year-old male patient with poorly differentiated metastatic lung adenocarcinoma, after 9 weeks exposure of sintilimab (3 doses) combined with paclitaxel liposome after concurrent chemotherapy/radiotherapy, experienced Stevens-Johnson syndrome involving limbs, trunk, lip and the oral mucosa. Biopsy of the skin tissue showed infiltration of CD4 and CD8 positive T lymphocytes. We also found PD-L1 expression in the glands and the basal layer of the skin. This finding is distinct from the previously reported expression of PD-L1 on the surface of epidermal keratinocytes in patients with SJS due to immunotherapy.
PubMed: 37781182
DOI: 10.3389/fonc.2023.912168 -
ACS Omega Sep 2023Nanoparticles have been suggested as drug-delivery systems for chemotherapeutic drugs to allow for controlled drug release profiles and selectivity to target cancer...
Nanoparticles have been suggested as drug-delivery systems for chemotherapeutic drugs to allow for controlled drug release profiles and selectivity to target cancer cells. In addition, nanoparticles can be used for the in situ generation and amplification of reactive oxygen species (ROS), which have been shown to be a promising strategy for cancer treatment. Thus, a targeted nanoscale drug-delivery platform could be used to synergistically improve cancer treatment by the action of chemotherapeutic drugs and ROS generation. Herein, we propose a promising chemotherapy strategy where the drug-loaded nanoparticles generate high doses of ROS together with the loaded ROS-generating chemotherapeutic drugs, which can damage the mitochondria and activate cell death, potentiating the therapeutic outcome in cancer therapy. In the present study, we have developed a dual-targeted drug-delivery nanoassembly consisting of a mesoporous silica core loaded with the chemotherapeutic, ROS-generating drug, paclitaxel (Px), and coated with a liposome layer for controlled drug release. Two different lung cancer-targeting ligands, folic acid and peptide GE11, were used to target the overexpressed nonsmall lung cancer receptors to create the final nanoassembly (MSN@Px) L-GF. Upon endocytosis by the cancer cells, the liposome layer was degraded by the intracellular lipases, and the drug was rapidly released at a rate of 65% within the first 20 h. In vitro studies confirmed that this nanoassembly was 8-fold more effective in cancer therapy compared to the free drug Px.
PubMed: 37779923
DOI: 10.1021/acsomega.3c02901 -
Biological & Pharmaceutical Bulletin 2023Niosomes are non-ionic surfactant (NIS)-based bilayer vesicles and, like liposomes, have great potential as drug-delivery systems. Our previous study revealed that...
Niosomes are non-ionic surfactant (NIS)-based bilayer vesicles and, like liposomes, have great potential as drug-delivery systems. Our previous study revealed that polyethylene glycol (PEG) niosomes using different sorbitan ester (Span) surfactants (sorbitan monoester, Span 20, 40, 60, 80; sorbitan triester, Span 65) distributed within tumors similarly to PEG liposomes. The aim of this study was to encapsulate efficiently an anti-cancer drug, paclitaxel (PTX) into Span PEG niosomes, and evaluate PTX release profiles and anti-tumor efficacy of PTX-loaded Span PEG niosomes. Niosome sizes ranged between 100-150 nm, and the PTX encapsulation efficiency was more than 50%. All niosomes examined, in the presence of serum, yielded sustained PTX-release profiles. PTX release at 24 and 48 h from Span 80 PEG niosomes was significantly the highest among the other Span PEG niosomes examined. In C26 tumor-bearing mice, PTX-loaded Span 40 PEG niosomes (the lowest PTX release in vitro) suppressed tumor growth while PTX-loaded Span 80 PEG niosomes (the highest PTX release in vitro) did not. Thus, we succeeded in the control of PTX release from Span PEG niosomes by modifying the component of niosomes, and it influenced the effects of drugs loaded into niosomes. This demonstrates that the excellent NIS physicochemical properties of Spans make them an ideal candidate for anti-cancer drug-carrier niosomes.
Topics: Mice; Animals; Liposomes; Paclitaxel; Polyethylene Glycols; Antineoplastic Agents; Drug Carriers; Surface-Active Agents
PubMed: 37779050
DOI: 10.1248/bpb.b23-00188 -
Asian Pacific Journal of Cancer... Sep 2023Addressing both the initial treatment response and subsequent paclitaxel resistance is a pivotal concern. Nano drug delivery, an emerging approach, presents a...
OBJECTIVE
Addressing both the initial treatment response and subsequent paclitaxel resistance is a pivotal concern. Nano drug delivery, an emerging approach, presents a cutting-edge alternative to conventional chemotherapy.
METHODS
This investigation synthesized PEGylated nanoparticles (NPs) via the Reverse Phase Evaporation technique for liposomal NPs. Characteristics such as zeta potential, size, drug release and polydispersity index (PDI) were subjected to evaluation. Subsequently, cytotoxicity assays were conducted on gastric cancer cells (AGS) following 24 and 48-hour incubation periods.
RESULTS
In this study, the liposomal NPs had a zeta potential of -22 mV and a particle size of 285 nm. The Entrapment efficiency was determined as 41% that occurred physically. Additionally, the liposomal NPs demonstrated a high drug retention rate (39% remained after 72 hours), and they exhibited significantly increased cytotoxicity compared to the free drug, confirming their effectiveness as a suitable carrier for paclitaxel during both incubation periods (P<0.05).
CONCLUSION
These findings collectively advocate the potential of liposomal NPs as promising contenders for effective nano-drug application in propelling chemotherapy forward.
Topics: Humans; Stomach Neoplasms; Antineoplastic Agents; Paclitaxel; Liposomes; Nanoparticles; Particle Size; Drug Carriers
PubMed: 37774084
DOI: 10.31557/APJCP.2023.24.9.3291 -
World Journal of Psychiatry Sep 2023Few relevant literature reports on applying acupoint press-needle embedding combined with emotional nursing in patients with a gynecological malignant tumor.
BACKGROUND
Few relevant literature reports on applying acupoint press-needle embedding combined with emotional nursing in patients with a gynecological malignant tumor.
AIM
To explore the effect of traditional Chinese medicine acupoint needle embedding combined with emotional nursing on chemotherapy-related nausea and vomiting (CINV), cancer-related fatigue (CRF) and psychological state in patients with gynecological malignant tumors.
METHODS
Retrospective analysis of the clinical information of 84 patients with gynecological malignant tumors treated in our hospital from August 2020 to December 2022 Led to the development of an observation group ( = 42) and a control group ( = 42) based on various nursing approaches. Ondansetron hydrochloride injection was administered to the individuals in the control group. However, the observation group received emotional nursing based on the control group and acupoint press-needle embedding of traditional Chinese medicine. Patients in both groups received the chemotherapy regimen of paclitaxel liposome + carbo-platin/ cisplatin. For four weeks, both groups intervened. The CINV grade, quality of life, CRF, psychological status and sleep quality scores of the two groups before and after intervention were compared.
RESULTS
After intervention, the degree of CINV in the observation group was significantly better than that in the control group. After intervention, the scores of each dimension and total score of FLIE scale were significantly higher than those in the control group. After intervention, the scores of each dimension and total score of Piper Fatigue Scale were significantly lower than those in the control group ( < 0.05). After intervention, the scores of avoidance and yield dimensions in the observation group were significantly lower than those in the control group, and the scores of confrontation dimension were significantly higher than those in the control group ( < 0.05). After intervention, the sleep quality score of the observation group was significantly lower than that of the control group, and the Karnofsky Performance Status scale score was significantly higher than that of the control group ( < 0.05).
CONCLUSION
The acupuncture point needle embedding of traditional Chinese medicine combined with emotional nursing can further reduce the incidence of chemotherapy-related nausea and vomiting in patients with gynecological malignant tumors, improve the quality of life and the degree of CRF, alleviate the bad psychological state, adopt a positive way to face the disease and treatment, and improve the quality of sleep and quality of life.
PubMed: 37771638
DOI: 10.5498/wjp.v13.i9.645 -
European Journal of Pharmaceutics and... Nov 2023Pancreatic cancer (PC) is an incurable disease with a high death rate in the world nowadays. Gemcitabine (GEM) and Paclitaxel (PTX) are considered as references of... (Review)
Review
Pancreatic cancer (PC) is an incurable disease with a high death rate in the world nowadays. Gemcitabine (GEM) and Paclitaxel (PTX) are considered as references of chemotherapeutic treatments and are commonly used in clinical applications. Factors related to the tumor microenvironment such as insufficient tumor penetration, toxicity, and drug resistance can limit the effectiveness of these therapeutic anticancer drugs. The use of different liposomal nanostructures is a way that can optimize the drug's effectiveness and reduce toxicity. Given the development of PC therapy, this review focuses on advances in Nano-formulation, characterization, and delivery systems of loaded GEM and PTX liposomes using chemotherapy, nucleic acid delivery, and stroma remodeling therapy. As a result, the review covers the literature dealing with the applications of liposomes in PC therapy.
Topics: Humans; Gemcitabine; Paclitaxel; Liposomes; Deoxycytidine; Cell Line, Tumor; Pancreatic Neoplasms; Nanostructures; Tumor Microenvironment
PubMed: 37758121
DOI: 10.1016/j.ejpb.2023.09.014 -
The Journal of International Medical... Sep 2023To compare the efficacy of paclitaxel liposomes combined with carboplatin and paclitaxel combined with carboplatin in the treatment of advanced ovarian cancer and assess... (Observational Study)
Observational Study
OBJECTIVE
To compare the efficacy of paclitaxel liposomes combined with carboplatin and paclitaxel combined with carboplatin in the treatment of advanced ovarian cancer and assess their effects on serum human epididymis protein 4 (HE4), CA125, CA199, matrix metalloproteinase-2 (MMP2), MMP-7, and MMP-9 levels.
METHODS
In this observational study, 102 patients with advanced ovarian cancer were assigned to receive paclitaxel liposomes combined with carboplatin (Group A) or paclitaxel combined with carboplatin (Group B). Clinical efficacy; serum HE4, CA125, CA199, MMP-2, MMP-7, and MMP-9 levels; and the occurrence of adverse reactions were compared between the groups.
RESULTS
The overall response rate was significantly higher in Group A than in Group B. After chemotherapy, serum HE4, CA125, CA199, MMP-2, MMP-7, and MMP-9 levels were lower in Group A than in Group B. The incidence of myalgia, dyspnea, nausea and vomiting, facial flushing, peripheral neuropathy, and skin rash was lower in Group A than in Group B.
CONCLUSION
Paclitaxel liposomes combined with carboplatin displayed better efficacy in the treatment of advanced ovarian cancer than paclitaxel combined with carboplatin, which might be attributable to reductions in serum marker levels and the occurrence of adverse events.
Topics: Female; Humans; Matrix Metalloproteinase 2; Carboplatin; Liposomes; Matrix Metalloproteinase 7; Matrix Metalloproteinase 9; Paclitaxel; CA-125 Antigen; Carcinoma, Ovarian Epithelial; Ovarian Neoplasms
PubMed: 37756606
DOI: 10.1177/03000605231200267 -
Environmental Research Dec 2023The site-specific delivery of drugs, especially anti-cancer drugs has been an interesting field for researchers and the reason is low accumulation of cytotoxic drugs in... (Review)
Review
The site-specific delivery of drugs, especially anti-cancer drugs has been an interesting field for researchers and the reason is low accumulation of cytotoxic drugs in cancer cells. Although combination cancer therapy has been beneficial in providing cancer drug sensitivity, targeted delivery of drugs appears to be more efficient. One of the safe, biocompatible and efficient nano-scale delivery systems in anti-cancer drug delivery is liposomes. Their particle size is small and they have other properties such as adjustable physico-chemical properties, ease of functionalization and high entrapment efficiency. Cisplatin is a chemotherapy drug with clinical approval in patients, but its accumulation in cancer cells is low due to lack of targeted delivery and repeated administration results in resistance development. Gene and drug co-administration along with cisplatin/paclitaxel have resulted in increased sensitivity in tumor cells, but there is still space for more progress in cancer therapy. The delivery of cisplatin/paclitaxel by liposomes increases accumulation of drug in tumor cells and impairs activity of efflux pumps in promoting cytotoxicity. Moreover, phototherapy along with cisplatin/paclitaxel delivery can increase potential in tumor suppression. Smart nanoparticles including pH-sensitive nanoparticles provide site-specific delivery of cisplatin/paclitaxel. The functionalization of liposomes can be performed by ligands to increase targetability towards tumor cells in mediating site-specific delivery of cisplatin/paclitaxel. Finally, liposomes can mediate co-delivery of cisplatin/paclitaxel with drugs or genes in potentiating tumor suppression. Since drug resistance has caused therapy failure in cancer patients, and cisplatin/paclitaxel are among popular chemotherapy drugs, delivery of these drugs mediates targeted suppression of cancers and prevents development of drug resistance. Because of biocompatibility and safety of liposomes, they are currently used in clinical trials for treatment of cancer patients. In future, the optimal dose of using liposomes and optimal concentration of loading cisplatin/paclitaxel on liposomal nanocarriers in clinical trials should be determined.
Topics: Humans; Liposomes; Cisplatin; Paclitaxel; Antineoplastic Agents; Drug Delivery Systems; Neoplasms; Cell Line, Tumor
PubMed: 37734579
DOI: 10.1016/j.envres.2023.117111 -
Nanomedicine : Nanotechnology, Biology,... Nov 2023There are four kinds of taxanes: solvent-based paclitaxel (Sb-P), liposomal paclitaxel (Lps-P), nanoparticle albumin-bound paclitaxel (Nab-P), and docetaxel. This study...
Efficacy comparisons of solvent-based paclitaxel, liposomal paclitaxel, nanoparticle albumin-bound paclitaxel, and docetaxel after neoadjuvant systemic treatment in breast cancer.
PURPOSE
There are four kinds of taxanes: solvent-based paclitaxel (Sb-P), liposomal paclitaxel (Lps-P), nanoparticle albumin-bound paclitaxel (Nab-P), and docetaxel. This study aims to retrospectively evaluate the efficacy of different taxanes on neoadjuvant systemic treatment (NST) in breast cancer.
METHODS
Patients who were diagnosed with breast cancer and had received integral NST from August 2013 to April 2022 were enrolled. The efficacy was divided into total pathological complete response (total-pCR), breast pathological complete response (breast-pCR), and axillary pathological complete response (axillary-pCR) for in-depth analysis and discussion.
RESULTS
The choice of taxane was an independent risk factor for total-pCR and breast-pCR rates. The highest total-pCR and breast-pCR rates were found in the Nab-P group. The difference was not significant among all the taxanes in the axillary-pCR rate.
CONCLUSION
Nab-P significantly improved the total-pCR and breast-pCR rates. It should be the first choice among taxanes in NST for breast cancer.
Topics: Humans; Female; Breast Neoplasms; Docetaxel; Albumin-Bound Paclitaxel; Neoadjuvant Therapy; Retrospective Studies; Paclitaxel; Albumins; Taxoids; Nanoparticles; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37717927
DOI: 10.1016/j.nano.2023.102707 -
Journal of Controlled Release :... Nov 2023It is time for the story of mitochondria and intracellular communication in multidrug resistant cancer to be rewritten. Herein we characterize the extent and cellular...
It is time for the story of mitochondria and intracellular communication in multidrug resistant cancer to be rewritten. Herein we characterize the extent and cellular advantages of mitochondrial network fusion in multidrug resistant (MDR) breast cancer and have designed a novel nanomedicine that disrupts mitochondrial network fusion and systematically manipulates organelle fusion and function. Combination Organelle Mitochondrial Endoplasmic reticulum Therapy (COMET) is an innovative translational nanomedicine for treating MDR triple negative breast cancer (TNBC) that has superior safety and equivalent efficacy to the current standard of care (paclitaxel). Our study has demonstrated that the increased mitochondrial networks in MDR TNBC contribute to apoptotic resistance and network fusion is mediated by mitofusin2 (MFN2) on the outer mitochondrial membrane. COMET consists of three components; Mitochondrial Network Disrupting (MiND) nanoparticles (NPs) that are loaded with an anti-MFN2 peptide, tunicamycin, and Bam7. The therapeutic rationale of COMET is to reduce the apoptotic threshold in MDR cells with MiND NPs, followed by inducing the endoplasmic reticulum mediated unfolded protein response (UPR) by stressing MDR cells with tunicamycin, and finally, directly inducing mitochondrial apoptosis with Bam7 which is a specific bcl-2 Bax activator. MiND NPs are PEGylated liposomes with the 21 amino acid (2577.98 MW) anti-MFN2 peptide compartmentalized in the aqueous core. Hypoxia (0.5% oxygen) was used to create MDR derivatives of MDA-MB-231 cells and BT-549 cells. Mitochondrial networks were quantified using 3D analysis of 60× live cell images acquired with a Keyence BZ-X710 microscope and MiND NPs effectively fragmented mitochondrial networks in drug sensitive and MDR TNBC cells. The IC values, combination index, and dose reduction index derived from dose response studies demonstrate that MiND NPs decrease the apoptotic threshold of both drug sensitive and MDR TNBC cells and COMET is a synergistic drug combination. Complex V (ATP synthase) extracted from bovine cardiac mitochondria was used to assess the effect of MiND NPs on OXPHOS; both MiND NPs and anti-MFN2 peptide solution significantly decrease the activity of mitochondrial complex V and decrease the capacity of OXPHOS. A BacMam viral vector based fluorescent biosensor was used to quantify the unfolded protein response (UPR) at the level of the endoplasmic reticulum and tunicamycin specifically induces the UPR in drug sensitive and MDR TNBC cells. A caspase 3 colorimetric assay demonstrated that the synergistic triple drug combination of COMET increases the ability of Bam7 to specifically induce apoptosis. Dose limiting toxicity and off target effects are a significant challenge for current chemotherapy regimens including paclitaxel. COMET has significantly lower cytotoxicity than paclitaxel in human embryonic kidney epithelial cells and has the potential to fulfill the clinical need for safer cancer therapeutics. COMET is a promising early stage translational nanomedicine for treating MDR TNBC. Manipulating intracellular communication and organelle fusion is a novel approach to treating MDR cancer. The data from this study has rewritten the story of mitochondria, organelle fusion, and intracellular communication and by targeting this intersection, COMET is an exciting new chapter in cancer therapeutics that could transform the clinical outcome of MDR TNBC.
Topics: Animals; Cattle; Humans; Drug Resistance, Multiple; Triple Negative Breast Neoplasms; Tunicamycin; Drug Resistance, Neoplasm; Paclitaxel; Mitochondria; Apoptosis; Endoplasmic Reticulum; Peptides; Drug Combinations; Cell Line, Tumor
PubMed: 37717658
DOI: 10.1016/j.jconrel.2023.09.023