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Wiley Interdisciplinary Reviews.... 2024Coronary stents have saved millions of lives in the last three decades by treating atherosclerosis especially, by preventing plaque protrusion and subsequent aneurysms.... (Review)
Review
Coronary stents have saved millions of lives in the last three decades by treating atherosclerosis especially, by preventing plaque protrusion and subsequent aneurysms. They attenuate the vascular SMC proliferation and promote reconstruction of the endothelial bed to ensure superior revascularization. With the evolution of modern stent types, nanotechnology has become an integral part of stent technology. Nanocoating and nanosurface fabrication on metallic and polymeric stents have improved their drug loading capacity as well as other mechanical, physico-chemical, and biological properties. Nanofeatures can mimic the natural nanofeatures of vascular tissue and control drug-delivery. This review will highlight the role of nanotechnology in addressing the challenges of coronary stents and the recent advancements in the field of related medical devices. Different generations of stents carrying nanoparticle-based formulations like liposomes, lipid-polymer hybrid NPs, polymeric micelles, and dendrimers are discussed highlighting their roles in local drug delivery and anti-restenotic properties. Drug nanoparticles like Paclitaxel embedded in metal stents are discussed as a feature of first-generation drug-eluting stents. Customized precision stents ensure safe delivery of nanoparticle-mediated genes or concerted transfer of gene, drug, and/or bioactive molecules like antibodies, gene mimics via nanofabricated stents. Nanotechnology can aid such therapies for drug delivery successfully due to its easy scale-up possibilities. However, limitations of this technology such as their potential cytotoxic effects associated with nanoparticle delivery that can trigger hypersensitivity reactions have also been discussed in this review. This article is categorized under: Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement Therapeutic Approaches and Drug Discovery > Nanomedicine for Cardiovascular Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.
Topics: Stents; Drug-Eluting Stents; Nanotechnology; Antineoplastic Agents; Paclitaxel
PubMed: 38528392
DOI: 10.1002/wnan.1941 -
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 -
Frontiers in Oncology 2024Photodynamic therapy (PDT) involves the administration of a photosensitizing agent and irradiation of light at an excitation wavelength that damages tumor cells without...
BACKGROUND
Photodynamic therapy (PDT) involves the administration of a photosensitizing agent and irradiation of light at an excitation wavelength that damages tumor cells without causing significant damage to normal tissue. We developed indocyanine green (ICG)-modified liposomes in which paclitaxel (PTX) was encapsulated (ICG-Lipo-PTX). ICG-Lipo-PTX accumulates specifically in tumors due to the characteristics of the liposomes. The thermal and photodynamic effects of ICG and the local release of PTX by irradiation are expected to induce not only antitumor effects but also cancer immunity. In this study, we investigated the antitumor effects of ICG-Lipo-PTX in breast cancer.
METHODS
The antitumor effects of ICG-Lipo-PTX were examined in xenograft model mice subcutaneously implanted with KPL-1 human breast cancer cells. ICG-Lipo-PTX, ICG-Lipo, or saline was administered intraperitoneally, and the fluorescence intensity was measured with a fluorescence imaging system (IVIS). Intratumor temperature, tumor volume, and necrotic area of tumor tissue were also compared. Next, we investigated the induction of cancer immunity in an allogeneic transplantation model in which BALB-MC mouse breast cancer cells were transplanted subcutaneously in the bilateral inguinal region. ICG-Lipo-PTX was administered intraperitoneally, and PDT was performed on only one side. The fluorescence intensity measured by IVIS and the bilateral tumor volumes were compared. Cytokine secretory capacity was also evaluated by ELISPOT assay using splenocytes.
RESULTS
In the xenograft model, the fluorescence intensity and temperature during PDT were significantly higher with ICG-Lipo-PTX and ICG-Lipo in tumor areas than in nontumor areas. The fluorescence intensity in the tumor area was reduced to the same level as that in the nonirradiated area after two times of irradiation. Tumor growth was significantly reduced and the percentage of necrotic area in the tumor was higher after PDT in the ICG-Lipo-PTX group than in the other groups. In the allograft model, tumor growth on day 14 in the ICG-Lipo-PTX group was significantly suppressed not only on the PDT side but also on the non-PDT side. In addition, the secretion of interferon-γ and interleukin-2 was enhanced, whereas that of interleukin-10 was suppressed, in the ICG-Lipo-PTX group.
CONCLUSION
The PDT therapy with ICG-Lipo-PTX may be an effective treatment for breast cancer.
PubMed: 38515576
DOI: 10.3389/fonc.2024.1365305 -
Journal of Controlled Release :... Apr 2024Liposomes are widely used as drug delivery nanoplatforms because of their versatility and biocompatibility; however, their ability to load certain drugs may be...
Liposomes are widely used as drug delivery nanoplatforms because of their versatility and biocompatibility; however, their ability to load certain drugs may be suboptimal. In this study, we generated liposomes using a combination of DSPE and DSPE-PEG-2 k lipids and loaded them with doxorubicin (DOX) and paclitaxel (PTX), to investigate the effects of light emitting diode (LED) irradiation on liposome structure and drug loading efficiency. Scanning and transmission electron microscopy revealed that the surface of liposomes irradiated with blue or near-infrared LEDs (LsLipo) was rougher and more irregular than that of non-LED-irradiated liposomes (NsLipo). Nuclear magnetic resonance analysis showed that the hydrogen peak originating from the lipid head groups was lower in LsLipo than in NsLipo preparations, indicating that LED irradiation changed the chemical and physical properties of the liposome. Structural changes, such as reduced rigidity, induced by LED irradiation, increased the loading efficiency of DOX and PTX. In vitro and in vivo experiments showed that LsLipo were more effective at inhibiting the growth of cancer cells than NsLipo. Our findings suggest that LED irradiation enhances the drug delivery efficacy of liposomes and offer new possibilities for improving drug delivery systems.
Topics: Humans; Liposomes; Drug Delivery Systems; Paclitaxel; Doxorubicin; Neoplasms; Cell Line, Tumor
PubMed: 38499090
DOI: 10.1016/j.jconrel.2024.03.027 -
Chinese Journal of Cancer Research =... Feb 2024Despite cardiotoxicity overlap, the trastuzumab/pertuzumab and anthracycline combination remains crucial due to significant benefits. Pegylated liposomal doxorubicin...
Sequential neoadjuvant chemotherapy using pegylated liposomal doxorubicin and cyclophosphamide followed by taxanes with complete trastuzumab and pertuzumab treatment for HER2-positive breast cancer: A phase II single-arm study.
OBJECTIVE
Despite cardiotoxicity overlap, the trastuzumab/pertuzumab and anthracycline combination remains crucial due to significant benefits. Pegylated liposomal doxorubicin (PLD), a less cardiotoxic anthracycline, was evaluated for efficacy and cardiac safety when combined with cyclophosphamide and followed by taxanes with trastuzumab/pertuzumab in human epidermal growth factor receptor-2 (HER2)-positive early breast cancer (BC).
METHODS
In this multicenter, phase II study, patients with confirmed HER2-positive early BC received four cycles of PLD (30-35 mg/m) and cyclophosphamide (600 mg/m), followed by four cycles of taxanes (docetaxel, 90-100 mg/m or nab-paclitaxel, 260 mg/m), concomitant with eight cycles of trastuzumab (8 mg/kg loading dose, then 6 mg/kg) and pertuzumab (840 mg loading dose, then 420 mg) every 3 weeks. The primary endpoint was total pathological complete response (tpCR, ypT0/is ypN0). Secondary endpoints included breast pCR (bpCR), objective response rate (ORR), disease control rate, rate of breast-conserving surgery (BCS), and safety (with a focus on cardiotoxicity).
RESULTS
Between May 27, 2020 and May 11, 2022, 78 patients were treated with surgery, 42 (53.8%) of whom had BCS. After neoadjuvant therapy, 47 [60.3%, 95% confidence interval (95% CI), 48.5%-71.2%] patients achieved tpCR, and 49 (62.8%) achieved bpCR. ORRs were 76.9% (95% CI, 66.0%-85.7%) and 93.6% (95% CI, 85.7%-97.9%) after 4-cycle and 8-cycle neoadjuvant therapy, respectively. Nine (11.5%) patients experienced asymptomatic left ventricular ejection fraction (LVEF) reductions of ≥10% from baseline, all with a minimum value of >55%. No treatment-related abnormal cardiac function changes were observed in mean N-terminal pro-BNP (NT-proBNP), troponin I, or high-sensitivity troponin.
CONCLUSIONS
This dual HER2-blockade with sequential polychemotherapy showed promising activity with rapid tumor regression in HER2-positive BC. Importantly, this regimen showed an acceptable safety profile, especially a low risk of cardiac events, suggesting it as an attractive treatment approach with a favorable risk-benefit balance.
PubMed: 38455369
DOI: 10.21147/j.issn.1000-9604.2024.01.06 -
International Journal of Pharmaceutics Apr 2024Multidrug resistance (MDR) poses a significant impediment to the efficacy of chemotherapy in clinical settings. Despite Paclitaxel (PTX) being designated as the primary...
Multidrug resistance (MDR) poses a significant impediment to the efficacy of chemotherapy in clinical settings. Despite Paclitaxel (PTX) being designated as the primary pharmaceutical agent for treating recurrent and metastatic breast cancer, the emergence of PTX resistance frequently results in therapeutic shortcomings, representing a substantial obstacle in clinical breast cancer management. In response, we developed a delivery system exhibiting dual specificity for both tumors and mitochondria. This system facilitated the sequential administration of small interfering B-cell lymphoma-2 (siBcl-2) and PTX to the tumor cytoplasm and mitochondria, respectively, with the aim of surmounting PTX resistance in tumor cells through the activation of the mitochondrial apoptosis pathway. Notably, we employed genetic engineering techniques to fabricate a recombinant ferritin containing the H-subunit (HFn), known for its tumor-targeting capabilities, for loading siBcl-2. This HFn-siBcl-2 complex was then combined with positively charged Triphenylphosphine-Liposome@PTX (TL@PTX) nanoparticles (NPs) to formulate HFn/siBcl-2@TL/PTX. Guided by HFn, these nanoparticles efficiently entered cells and released siBcl-2 through the action of triphenylphosphine (TPP)-mediated "proton sponge," thereby precisely modulating the expression of Bcl-2 protein. Simultaneously, PTX was directed to the mitochondria through the accurate targeting of TL@PTX, synergistically initiating the mitochondrial apoptosis pathway and effectively suppressing PTX resistance both in vitro and in vivo. In conclusion, the development of this dual-targeting delivery system presents a promising therapeutic strategy for overcoming PTX resistance in the clinical treatment of breast cancer.
Topics: Humans; Female; Paclitaxel; Drug Resistance, Neoplasm; Mitochondria; Breast Neoplasms; Drug Resistance, Multiple; Nanoparticles; Cell Line, Tumor; Drug Delivery Systems; Organophosphorus Compounds
PubMed: 38447779
DOI: 10.1016/j.ijpharm.2024.123970 -
Biomedical Materials (Bristol, England) Mar 2024Breast cancer (BC) is one of the most common cancers in women, and chemotherapy is usually used to overcome this cancer. To improve drug delivery to cancer sites and...
Breast cancer (BC) is one of the most common cancers in women, and chemotherapy is usually used to overcome this cancer. To improve drug delivery to cancer sites and reduce their side effects, nanocarriers such as niosomes (NIOs) are used. Moreover, a combination of other therapeutic methods like photothermal therapy (PTT) can help to enhance the chemotherapy effect. The aim of this research is the design a nanocarrier that simultaneously delivers chemotherapy and PTT agents. To achieve this goal, NIOs containing paclitaxel (PTX) as a chemotherapeutic agent and spherical gold nanoparticles (AuNPs) coated with citrate, chitosan (CS), and polyamidoamine (PAMAM) as a PTT agent were synthesized by thin hydration methods. Their physicochemical properties were determined by dynamic light scattering, UV-Vis, Fourier-transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM) analysis. Cellular uptake, cell cytotoxicity, hyperthermia, and apoptosis effects of the proposed system were investigated in the MCF-7 BC cell line. The cellular uptake of NIOs/AuNPs-PAMAM (99.21%) and NIOs/AuNPs-CS (98.93%) by MCF-7 cells was higher than that of NIOs/AuNPs (79.55%), demonstrating that surface charge plays a key role in the cellular uptake of NPs. The MTT assay showed the cell viability of 45.48% for NIOs/AuNPs/PTX, 34.24% for NIOs/AuNPs-CS/PTX, and 37.67% for NIOs/AuNPs-PAMAM/PTX after 48 h of treatment. However, the application of hyperthermia significantly decreased the viability of cells treated with NIOs/AuNPs/PTX (37.72%), NIOs/AuNPs-CS/PTX (10.49%), and NIOs/AuNPs-PAMAM/PTX (4.1%) after 48 h. The apoptosis rate was high in NIOs/AuNPs-PAMAM/PTX (53.24%) and NIOs/AuNPs-CS/PTX (55.4%) confirming the data from MTT. In conclusion, the result revealed that combined PTT with chemotherapy increased cell cytotoxicity effects against the MCF-7 cells, and the AuNPs with various coating agents affected cellular uptake and hyperthermia which can be considered for efficient BC therapy.
Topics: Female; Humans; Paclitaxel; Breast Neoplasms; Gold; Liposomes; Photothermal Therapy; Spectroscopy, Fourier Transform Infrared; Metal Nanoparticles; Nanoparticles; Chitosan; Cell Line, Tumor
PubMed: 38422524
DOI: 10.1088/1748-605X/ad2ed5 -
Molecular Pharmaceutics Apr 2024Cationic lipids play a pivotal role in developing novel drug delivery systems for diverse biomedical applications, owing to the success of mRNA vaccines against COVID-19...
Cationic lipids play a pivotal role in developing novel drug delivery systems for diverse biomedical applications, owing to the success of mRNA vaccines against COVID-19 and the Phase III antitumor agent EndoTAG-1. However, the therapeutic potential of these positively charged liposomes is limited by dose-dependent toxicity. While an increased content of cationic lipids in the formulation can enhance the uptake and cytotoxicity toward tumor-associated cells, it is crucial to balance these advantages with the associated toxic side effects. In this work, we synthesized the cationic lipid HC-Y-2 and incorporated it into sialic acid (SA)-modified cationic liposomes loaded with paclitaxel to target tumor-associated immune cells efficiently. The SA-modified cationic liposomes exhibited enhanced binding affinity toward both RAW264.7 cells and 4T1 tumor cells due to the increased ratios of cationic HC-Y-2 content while effectively inhibiting 4T1 cell lung metastasis . By leveraging electrostatic forces and ligand-receptor interactions, the SA-modified cationic liposomes specifically target malignant tumor-associated immune cells such as tumor-associated macrophages (TAMs), reduce the proportion of cationic lipids in the formulation, and achieve dual objectives: high cellular uptake and potent antitumor efficacy. These findings highlight the potential advantages of this innovative approach utilizing cationic liposomes.
Topics: Humans; Female; Liposomes; N-Acetylneuraminic Acid; Breast Neoplasms; COVID-19 Vaccines; Paclitaxel; Lung Neoplasms; Lipids; Cations; Cell Line, Tumor
PubMed: 38403951
DOI: 10.1021/acs.molpharmaceut.3c00767 -
BMC Cancer Feb 2024Advanced pancreatic cancer is one of the leading causes of cancer-related deaths. For patients with advanced pancreatic cancer, gemcitabine and nanoparticle...
Efficacy of adding levofloxacin to gemcitabine and nanoparticle-albumin-binding paclitaxel combination therapy in patients with advanced pancreatic cancer: study protocol for a multicenter, randomized phase 2 trial (T-CORE2201).
BACKGROUND
Advanced pancreatic cancer is one of the leading causes of cancer-related deaths. For patients with advanced pancreatic cancer, gemcitabine and nanoparticle albumin-binding paclitaxel (nabPTX) combination (GEM/nabPTX) therapy is one of the recommended first-line treatments. Several retrospective studies have suggested that the addition of levofloxacin improves the efficacy of GEM/nabPTX therapy in patients with advanced pancreatic cancer. This prospective study aims to evaluate whether the addition of antibiotics improves the treatment efficacy of GEM/nabPTX as a first-line chemotherapy in patients with advanced pancreatic cancer.
METHODS
This multicenter, prospective, randomized, phase 2 trial will included 140 patients. Patients with advanced pancreatic cancer will be randomized in a 1:1 ratio to either the GEM/nabPTX therapy group or the GEM/nabPTX plus levofloxacin group. The primary endpoint for the two groups is median progression-free survival time (mPFS) for the full analysis set (FAS). The secondary endpoints for the two groups are median overall survival (mOS), response rate (RR), disease control rate (DCR), and adverse event (AE) for the FAS and mPFS, mOS, RR, DCR, and AE for the per-protocol set. This study will enroll patients treated with GEM/nabPTX as the first-line chemotherapy for stage IV pancreatic adenocarcinoma.
DISCUSSION
GEM/nabPTX is a standard first-line chemotherapy regimen for patients with advanced pancreatic cancer. Recently, the superiority of 5-fluorouracil, liposomal irinotecan, and oxaliplatin combination therapy (NALIRIFOX) to GEM/nabPTX as first-line therapy for pancreatic cancer has been reported. However, the efficacy of NALIRIFOX is inadequate. Based on previous retrospective studies, it is hypothesized that treatment efficacy will improve when levofloxacin is added to GEM/nabPTX therapy. If the AEs (such as leukopenia, neutropenia, and peripheral neuropathy) that occur at an increased rate with levofloxacin and GEM/nabPTX combination therapy can be carefully monitored and properly managed, this simple intervention can be expected to improve the prognosis of patients with advanced pancreatic cancer.
TRIAL REGISTRATION
This study was registered with the Japan Registry of Clinical Trials (jRCT; registry number: jRCTs021230005).
Topics: Humans; Adenocarcinoma; Albumins; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase II as Topic; Gemcitabine; Levofloxacin; Multicenter Studies as Topic; Nanoparticles; Paclitaxel; Pancreatic Neoplasms; Prospective Studies; Randomized Controlled Trials as Topic; Retrospective Studies
PubMed: 38402399
DOI: 10.1186/s12885-024-11973-9 -
RSC Advances Feb 2024There is a great demand for the technology of molecular delivery into living cells using nanocarriers to realise molecular therapies such as gene delivery and drug...
There is a great demand for the technology of molecular delivery into living cells using nanocarriers to realise molecular therapies such as gene delivery and drug delivery systems. Lipid-based nanocarriers offer several advantages for molecular delivery in biological systems, such as easy preparation, high encapsulation efficiency of water-insoluble drug molecules, and excellent biocompatibility. In this paper, we first report the interaction of lipid nanodiscs spontaneously formed by the complexation of an amphiphilic polymethacrylate derivative and phospholipid with intact cells. We evaluated the internalisation of polymethacrylate-based lipid nanodiscs by intact HeLa cells and applied them to the delivery of paclitaxel (PTX), an anticancer drug. The lipid nanodisc showed excellent uptake efficiency compared to conventional liposomes at a concentration where nanodiscs do not show cytotoxicity. In addition, the nanodisc encapsulating PTX showed significantly higher anticancer activity than PTX-loaded liposomes against HeLa cells, reflecting their excellent activity in delivering payloads to intact cells. This study demonstrated the potential of a polymethacrylate-based lipid nanodisc as a novel nanocarrier for molecular delivery to intact cells.
PubMed: 38375006
DOI: 10.1039/d3ra07481a