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Zhong Nan Da Xue Xue Bao. Yi Xue Ban =... Aug 2014To prepare Arg-Gly-Asp (RGD) and cell penetrating peptide TAT co-modified paclitaxel loaded liposome (RGD/TAT-LP-PTX) for MCF-7 cell inhibition.
OBJECTIVE
To prepare Arg-Gly-Asp (RGD) and cell penetrating peptide TAT co-modified paclitaxel loaded liposome (RGD/TAT-LP-PTX) for MCF-7 cell inhibition.
METHODS
The co-modified liposome was prepared by film-ultrasonic method. The appearance, particle size and zeta potential were evaluated. The cellular uptake by MCF-7 cells in vitro was used to evaluate the targeting efficiency. The anti-proliferation efficiency of RGD/TAT-LP-PTX was evaluated by MTT assay. Tumor spheroids were used to evaluate anti-tumor ability of RGD/TAT-LP-PTX in vitro.
RESULTS
The particle diameter of the co-modified liposome was (138.8 ± 12.4) nm with the Zeta potential of (25.85 ± 2.75) mV. The entrapment efficiency of PTX was 88.3%. The RGD/TAT-LP uptaken by MCF-7 cells at 4 h was 1.79 times higher than that at 2 h. The co-modified liposome uptaken by MCF-7 cells was 2.25 and 2.72 times higher than that of TAT-LP and RGD-LP, respectively. The anti-proliferation rate of RGD/TAT-LP-PTX increased with time. The inhibition rate of RGD/TAT-LP-PTX for MCF-7 cells at 48 h was 1.78 times higher than that at 24 h. The MTT assay demonstrated the cell viability of RGD/TAT-LP-PTX was 1.65, 1.82 and 2.55 times higher than that of TAT-LP-PTX, RGD-LP-PTX and LP-PTX, respectively.
CONCLUSION
Co-modified liposome may serve as a promising breast cancer delivery system for antitumor drugs.
Topics: Antineoplastic Agents; Breast Neoplasms; Cell Survival; Humans; Liposomes; MCF-7 Cells; Oligopeptides; Paclitaxel; Particle Size; Peptide Fragments; Spheroids, Cellular
PubMed: 25202944
DOI: 10.3969/j.issn.1672-7347.2014.08.003 -
Annals of Oncology : Official Journal... Sep 2012Lung cancer is the leading cause of cancer-related mortality worldwide, with non-small-cell lung cancer (NSCLC) accounting for approximately 85% of all cases. Most... (Review)
Review
Lung cancer is the leading cause of cancer-related mortality worldwide, with non-small-cell lung cancer (NSCLC) accounting for approximately 85% of all cases. Most patients with NSCLC are diagnosed at an advanced stage and have a poor prognosis, with a 5-year survival rate of <5%. Despite the introduction of new chemotherapeutic agents and molecularly targeted drugs, outcomes remain poor, emphasising the need for new treatment approaches. Inducing or potentiating immune responses via immunotherapeutic manipulation is a viable treatment approach for lung cancer. Antigen-specific, tumour-cell, and dendritic cell-based vaccines have all been evaluated in lung cancer, and some have shown promising clinical activity in phase II trials. These include liposomal BLP25 vaccine (L-BLP25), which targets mucin 1, and melanoma-associated antigen 3 (MAGE-A3) antigen-specific cancer immunotherapeutic (ASCI), which targets MAGE-A3, a peptide expressed almost exclusively on tumour cells. MAGE-A3 ASCI is being evaluated in the adjuvant setting in a phase III trial of patients with early-stage NSCLC, while a phase III trial of L-BLP25 is enrolling patients with unresectable stage III NSCLC. T-cell modulating agents (e.g. antibodies against programmed death 1 and cytotoxic T-lymphocyte-associated antigen-4 [CTLA-4]) are also being investigated. For example, in patients with NSCLC treated with paclitaxel and carboplatin, the phased administration of ipilimumab (an antibody against CTLA-4) resulted in substantial improvements in immune-related progression-free survival compared with chemotherapy alone (5.7 versus 4.6 months; P = 0.05). Immunotherapy in lung cancer is starting to deliver promising results in clinical trials. However, further research will be required to establish the optimal timing of therapy (i.e. in the adjuvant or metastatic settings). In addition, it will be important to determine if immunotherapies are most effective when used alone or in combination with other agents.
Topics: Antibodies, Monoclonal; Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; CTLA-4 Antigen; Cancer Vaccines; Carboplatin; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Humans; Immunotherapy; Ipilimumab; Lactoferrin; Lung Neoplasms; Membrane Glycoproteins; Neoplasm Proteins; Nivolumab; Paclitaxel
PubMed: 22918925
DOI: 10.1093/annonc/mds260 -
International Journal of Molecular... Sep 2018Tumours are complex systems of genetically diverse malignant cells that proliferate in the presence of a heterogeneous microenvironment consisting of host derived... (Review)
Review
Tumours are complex systems of genetically diverse malignant cells that proliferate in the presence of a heterogeneous microenvironment consisting of host derived microvasculature, stromal, and immune cells. The components of the tumour microenvironment (TME) communicate with each other and with cancer cells, to regulate cellular processes that can inhibit, as well as enhance, tumour growth. Therapeutic strategies have been developed to modulate the TME and cancer-associated immune response. However, modulating compounds are often insoluble (aqueous solubility of less than 1 mg/mL) and have suboptimal pharmacokinetics that prevent therapeutically relevant drug concentrations from reaching the appropriate sites within the tumour. Nanomedicines and, in particular, liposomal formulations of relevant drug candidates, define clinically meaningful drug delivery systems that have the potential to ensure that the right drug candidate is delivered to the right area within tumours at the right time. Following encapsulation in liposomes, drug candidates often display extended plasma half-lives, higher plasma concentrations and may accumulate directly in the tumour tissue. Liposomes can normalise the tumour blood vessel structure and enhance the immunogenicity of tumour cell death; relatively unrecognised impacts associated with using liposomal formulations. This review describes liposomal formulations that affect components of the TME. A focus is placed on formulations which are approved for use in the clinic. The concept of tumour immunogenicity, and how liposomes may enhance radiation and chemotherapy-induced immunogenic cell death (ICD), is discussed. Liposomes are currently an indispensable tool in the treatment of cancer, and their contribution to cancer therapy may gain even further importance by incorporating modulators of the TME and the cancer-associated immune response.
Topics: Animals; Antineoplastic Agents; Cell Death; Drug Delivery Systems; Humans; Liposomes; Neoplasms; T-Lymphocytes; Tumor Microenvironment
PubMed: 30261606
DOI: 10.3390/ijms19102922 -
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 -
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 -
International Journal of Nanomedicine 2017Breast cancer is the most common malignant disease in women worldwide, but the current drug therapy is far from optimal as indicated by the high death rate of breast... (Review)
Review
Breast cancer is the most common malignant disease in women worldwide, but the current drug therapy is far from optimal as indicated by the high death rate of breast cancer patients. Nanomedicine is a promising alternative for breast cancer treatment. Nanomedicine products such as Doxil and Abraxane have already been extensively used for breast cancer adjuvant therapy with favorable clinical outcomes. However, these products were originally designed for generic anticancer purpose and not specifically for breast cancer treatment. With better understanding of the molecular biology of breast cancer, a number of novel promising nanotherapeutic strategies and devices have been developed in recent years. In this review, we will first give an overview of the current breast cancer treatment and the updated status of nanomedicine use in clinical setting, then discuss the latest important trends in designing breast cancer nanomedicine, including passive and active cancer cell targeting, breast cancer stem cell targeting, tumor microenvironment-based nanotherapy and combination nanotherapy of drug-resistant breast cancer. Researchers may get insight from these strategies to design and develop nanomedicine that is more tailored for breast cancer to achieve further improvements in cancer specificity, antitumorigenic effect, antimetastasis effect and drug resistance reversal effect.
Topics: Albumin-Bound Paclitaxel; Antineoplastic Agents; Breast Neoplasms; Doxorubicin; Drug Delivery Systems; Female; Humans; Molecular Targeted Therapy; Nanomedicine; Neoplastic Stem Cells; Polyethylene Glycols; Receptor, ErbB-2; Tumor Microenvironment
PubMed: 28860754
DOI: 10.2147/IJN.S123437 -
Pharmacogenomics and Personalized... Sep 2013Ovarian cancer (OC) has the highest mortality rate of any gynecologic cancer, and patients generally have a poor prognosis due to high chemotherapy resistance and late... (Review)
Review
Ovarian cancer (OC) has the highest mortality rate of any gynecologic cancer, and patients generally have a poor prognosis due to high chemotherapy resistance and late stage disease diagnosis. Platinum-resistant OC can be treated with cytotoxic chemotherapy such as paclitaxel, topotecan, pegylated liposomal doxorubicin, and gemcitabine, but many patients eventually relapse upon treatment. Fortunately, there are currently a number of targeted therapies in development for these patients who have shown promising results in recent clinical trials. These treatments often target the vascular endothelial growth factor pathway (eg, bevacizumab and aflibercept), DNA repair mechanisms (eg, iniparib and olaparib), or they are directed against folate related pathways (eg, pemetrexed, farletuzumab, and vintafolide). As many targeted therapies are only effective in a subset of patients, there is an increasing need for the identification of response predictive biomarkers. Selecting the right patients through biomarker screening will help tailor therapy to patients and decrease superfluous treatment to those who are biomarker negative; this approach should lead to improved clinical results and decreased toxicities. In this review the current targeted therapies used for treating platinum-resistant OC are discussed. Furthermore, use of prognostic and response predictive biomarkers to define OC patient populations that may benefit from specific targeted therapies is also highlighted.
PubMed: 24109193
DOI: 10.2147/PGPM.S24943 -
International Journal of Molecular... Mar 2021Biocompatible nanoparticles (NPs) containing polymers, lipids (liposomes and micelles), dendrimers, ferritin, carbon nanotubes, quantum dots, ceramic, magnetic... (Review)
Review
Biocompatible nanoparticles (NPs) containing polymers, lipids (liposomes and micelles), dendrimers, ferritin, carbon nanotubes, quantum dots, ceramic, magnetic materials, and gold/silver have contributed to imaging diagnosis and targeted cancer therapy. However, only some NP drugs, including Doxil (liposome-encapsulated doxorubicin), Abraxane (albumin-bound paclitaxel), and Oncaspar (PEG-Asparaginase), have emerged on the pharmaceutical market to date. By contrast, several phytochemicals that were found to be effective in cultured cancer cells and animal studies have not shown significant efficacy in humans due to poor bioavailability and absorption, rapid clearance, resistance, and toxicity. Research to overcome these drawbacks by using phytochemical NPs remains in the early stages of clinical translation. Thus, in the current review, we discuss the progress in nanotechnology, research milestones, the molecular mechanisms of phytochemicals encapsulated in NPs, and clinical implications. Several challenges that must be overcome and future research perspectives are also described.
Topics: Animals; Antineoplastic Agents, Phytogenic; Drug Delivery Systems; Humans; Mononuclear Phagocyte System; Nanoparticles; Nanotechnology; Nanotubes, Carbon; Neoplasms; Phytochemicals; Quantum Dots
PubMed: 33808235
DOI: 10.3390/ijms22073571 -
Translational Oncology Jun 2021Chemotherapy induces a variety of immunological changes. Studying these effects can reveal opportunities for successful combining chemotherapy and immunotherapy....
Chemotherapy induces a variety of immunological changes. Studying these effects can reveal opportunities for successful combining chemotherapy and immunotherapy. Immuno-chemotherapeutic combinations in ovarian cancer are currently not generating the anticipated positive effects. To date, only scattered and inconsistent information is available about the immune-induced changes by chemotherapy in ovarian cancer. In this study, we compared six common chemotherapeutics used in ovarian cancer patients (carboplatin, paclitaxel, pegylated liposomal doxorubicin, gemcitabine, carboplatin-paclitaxel and carboplatin-gemcitabine) and studied their effects on the immune system in an ovarian cancer mouse model. Mice received a single chemotherapy or vehicle injection 21 days after tumor inoculation with ID8-fluc cells. One week after therapy administration, we collected peritoneal washings for flow cytometry, serum for cytokine analysis with cytometric bead array and tumor biopsies for immunohistochemistry. Carboplatin-paclitaxel showed the most favorable profile with a decrease in immunosuppressive cells in the peritoneal cavity and an increase of interferon-gamma in serum. In contrast, carboplatin-gemcitabine seemed to promote a hostile immune environment with an increase in regulatory T-cells in tumor tissue and an increase of macrophage-inflammatory-protein-1-beta in the serum.
PubMed: 33770618
DOI: 10.1016/j.tranon.2021.101076 -
Cancer Communications (London, England) Jan 2022Lipusu is the first commercialized liposomal formulation of paclitaxel and has demonstrated promising efficacy against locally advanced lung squamous cell carcinoma... (Randomized Controlled Trial)
Randomized Controlled Trial
Paclitaxel liposome for injection (Lipusu) plus cisplatin versus gemcitabine plus cisplatin in the first-line treatment of locally advanced or metastatic lung squamous cell carcinoma: A multicenter, randomized, open-label, parallel controlled clinical study.
BACKGROUND
Lipusu is the first commercialized liposomal formulation of paclitaxel and has demonstrated promising efficacy against locally advanced lung squamous cell carcinoma (LSCC) in a small-scale study. Here, we conducted a multicenter, randomized, phase 3 study to compare the efficacy and safety of cisplatin plus Lipusu (LP) versus cisplatin plus gemcitabine (GP) as first-line treatment in locally advanced or metastatic LSCC.
METHODS
Patients enrolled were aged between 18 to 75 years, had locally advanced (clinical stage IIIB, ineligible for concurrent chemoradiation or surgery) or metastatic (Stage IV) LSCC, had no previous systemic chemotherapy and at least one measurable lesion as per the Response Evaluation Criteria in Solid Tumors (version 1.1) before administration of the trial drug. The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety profiles. To explore the possible predictive value of plasma cytokines for LP treatment, plasma samples were collected from the LP group at baseline and first efficacy evaluation time and were then subjected to analysis by 45-Plex ProcartaPlex Panel 1 to detect the presence of 45 cytokines using the Luminex xMAP technology. The correlation between treatment outcomes and dynamic changes in the levels of cytokines were evaluated in preliminary analyses.
RESULTS
The median duration of follow-up was 15.4 months. 237 patients in the LP group and 253 patients in the GP group were included in the per protocol set (PPS). In the PPS, the median PFS was 5.2 months versus 5.5 months in the LP and GP group (hazard ratio [HR]: 1.03, P = 0.742) respectively. The median OS was 14.6 months versus 12.5 months in the LP and GP group (HR: 0.83, P = 0.215). The ORR (41.8% versus 45.9%, P = 0.412) and DCR (90.3% versus 88.1%, P = 0.443) were also similar between the LP and GP group. A significantly lower proportion of patients in the LP group experienced adverse events (AEs) leading to treatment interruptions (10.9% versus 26.4%, P < 0.001) or treatment termination (14.3% versus 23.1%, P = 0.011). The analysis of cytokine levels in the LP group showed that low baseline levels of 27 cytokines were associated with an increased ORR, and 15 cytokines were associated with improved PFS, with 14 cytokines, including TNF-α, IFN-γ, IL-6, and IL-8, demonstrating an overlapping trend.
CONCLUSION
The LP regimen demonstrated similar PFS, OS, ORR and DCR as the GP regimen for patients with locally advanced or metastatic LSCC but had more favorable toxicity profiles. The study also identified a spectrum of different cytokines that could be potentially associated with the clinical benefit in patients who received the LP regimen.
Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Deoxycytidine; Humans; Liposomes; Lung; Lung Neoplasms; Middle Aged; Paclitaxel; Young Adult; Gemcitabine
PubMed: 34699693
DOI: 10.1002/cac2.12225