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Frontiers in Pharmacology 2024Systemic chemotherapy is typically administered following radical gastrectomy for advanced stage. To attenuate systemic side effects, we evaluated the effectiveness of...
Systemic chemotherapy is typically administered following radical gastrectomy for advanced stage. To attenuate systemic side effects, we evaluated the effectiveness of regional chemotherapy using paclitaxel, albumin-paclitaxel, and liposome-encapsulated albumin-paclitaxel via subserosal injection in rat models employing nuclear medicine and molecular imaging technology. Nine Sprague Dawley rats were divided into three groups: paclitaxel ( = 3), albumin-paclitaxel nano-particles (APNs; = 3), and liposome-encapsulated APNs ( = 3). [I]Iodo-paclitaxel ([I]I-paclitaxel) was synthesized by conventional electrophilic radioiodination using -butylstannyl substituted paclitaxel as the precursor. Albumin-[I]iodo-paclitaxel nanoparticles ([I]APNs) were prepared using a desolvation technique. Liposome-encapsulated APNs (L-[I]APNs) were prepared by thin-film hydration using DSPE-PEG2000, HSPC, and cholesterol. The rats in each group were injected with each test drug into the subserosa of the stomach antrum. After predetermined times (30 min, 2, 4, 8 h, and 24 h), molecular images of nuclear medicine were acquired using single-photon emission computed tomography/computed tomography. Paclitaxel, APNs, and L-APNs showed a high cumulative distribution in the stomach, with L-APNs showing the largest area under the curve. Most drugs administered via the gastric subserosal route are distributed in the stomach and intestines, with a low uptake of less than 1% in other major organs. The time to reach the maximum concentration in the intestine for L-APNs, paclitaxel, and APNs was 6.67, 5.33, and 4.00 h, respectively. These preliminary results imply that L-APNs have the potential to serve as a novel paclitaxel preparation method for the regional treatment of gastric cancer.
PubMed: 38904000
DOI: 10.3389/fphar.2024.1381406 -
International Journal of Nanomedicine 2024Ovarian cancer is a fatal gynecologic malignancy with a high rate of abdominal metastasis. Chemotherapy still has a poor clinical prognosis for ovarian cancer patients,...
PURPOSE
Ovarian cancer is a fatal gynecologic malignancy with a high rate of abdominal metastasis. Chemotherapy still has a poor clinical prognosis for ovarian cancer patients, with cell proliferation and angiogenesis leading to invasion, migration, and recurrence. To overcome these obstacles, we constructed a novel HA-modified paclitaxel and diosgenin liposome (PEG-TK-HA-PDLPs) using two novel functional materials, DSPE-PEG-HA and DSPE-PEG-TK-PEG, to specifically deliver the drugs to the tumor site in order to reduce OC cell proliferation and anti-angiogenic generation, thereby inhibiting invasion and migration.
METHODS AND RESULTS
PEG-TK-HA-PDLPs were prepared by film dispersion, with ideal physicochemical properties and exhibits active targeting for enhanced cellular uptake. The ZIP synergy score for PTX and Dios was calculated using the online SynergyFinder software to be 3.15, indicating synergy. In vitro results showed that PEG-TK-HA-PDLPs were highly cytotoxic to ID8 cells, induced ID8 cell apoptosis, and inhibited ID8 cell migration and invasion. In vivo studies showed that PEG-TK-HA-PDLPs could prolong the circulation time in the blood, accumulate significantly in the tumor site, and effectively fight against angiogenesis with significant anti-tumor effects.
CONCLUSION
The production of PEG-TK-HA-PDLPs is an effective strategy for the treatment of OC.
Topics: Female; Liposomes; Paclitaxel; Ovarian Neoplasms; Diosgenin; Hyaluronic Acid; Cell Line, Tumor; Polyethylene Glycols; Animals; Reactive Oxygen Species; Humans; Apoptosis; Drug Synergism; Cell Proliferation; Cell Movement; Mice; Mice, Inbred BALB C; Mice, Nude; Phosphatidylethanolamines
PubMed: 38859958
DOI: 10.2147/IJN.S455942 -
ACS Nano Jun 2024Triple-negative breast cancer (TNBC) is a highly aggressive malignancy that lacks effective targeted therapies. Inducing immunogenic cell death (ICD) in tumor cells...
Triple-negative breast cancer (TNBC) is a highly aggressive malignancy that lacks effective targeted therapies. Inducing immunogenic cell death (ICD) in tumor cells represents a promising strategy to enhance therapeutic efficacy by promoting antitumor immunity. Paclitaxel (PTX), a commonly used chemotherapy drug for TNBC, can induce ICD; however, the resulting immunogenicity is limited. Thus, there is an urgent need to explore strategies that improve the effectiveness of ICD in TNBC by incorporating immunoregulatory agents. This study investigated the potential of celecoxib (CXB) to enhance PTX-induced ICD by blocking the biosynthesis of PGE in the tumor cells. We observed that the combination of CXB and PTX promoted the maturation of dendritic cells and primed a T cell-dependent immune response, leading to enhanced tumor rejection in a vaccination assay. To further optimize drug delivery , we developed cRGD-modified liposomes for the targeted codelivery of CXB and PTX. This delivery system significantly improved drug accumulation and triggered robust antitumor immunity in an orthotopic mouse model of TNBC. Moreover, it served as an in situ vaccine to inhibit tumor recurrence and lung metastasis. Overall, our findings provide in-depth insights into the therapeutic mechanism underlying the combination of CXB and PTX, highlighting their potential as effective immune-based therapies for TNBC.
Topics: Triple Negative Breast Neoplasms; Celecoxib; Paclitaxel; Animals; Mice; Immunogenic Cell Death; Humans; Female; Cell Line, Tumor; Mice, Inbred BALB C; Liposomes
PubMed: 38829727
DOI: 10.1021/acsnano.4c02947 -
Current Pharmaceutical Biotechnology 2024Colorectal cancer (CRC) is a complex and multifactorial disorder in middle-aged people. Several modern medicines are available for treating and preventing it. However,... (Review)
Review
Colorectal cancer (CRC) is a complex and multifactorial disorder in middle-aged people. Several modern medicines are available for treating and preventing it. However, their therapeutic uses are limited due to drawbacks, such as gastric perforation, diarrhea, intestinal bleeding, abdominal cramps, hair loss, nausea, vomiting, weight loss, and adverse reactions. Hence, there is a continuous quest for safe and effective medicines to manage human health problems, like CRC. In this context, herbal medicines are considered an alternative disease control system. It has become popular in countries, like American, European, and Asian, due to its safety and effectiveness, which has been practiced for 1000 years. During the last few decades, herbal medicines have been widely explored through multidisciplinary fields for getting active compounds against human diseases. Several herbal bioactives, like curcumin, glycyrrhizin, paclitaxel, chlorogenic acid, gallic acid, catechin, berberine, ursolic acid, betulinic acid, chrysin, resveratrol, quercetin, etc., have been found to be effective against CRC. However, their pharmacological applications are limited due to low bioavailability and therapeutic efficacy apart from their several health benefits. An effective delivery system is required to increase their bioavailability and efficacy. Therefore, targeted novel drug delivery approaches are promising for improving these substances' solubility, bioavailability, and therapeutic effects. Novel carrier systems, such as liposomes, nanoparticles, micelles, microspheres, dendrimers, microbeads, and hydrogels, are promising for delivering poorly soluble drugs to the target site, i.e., the colon. Thus, the present review is focused on the pathophysiology, molecular pathways, and diagnostic and treatment approaches for CRC. Moreover, an emphasis has been laid especially on herbal bioactive-based novel delivery systems and their clinical updates.
Topics: Humans; Colorectal Neoplasms; Drug Carriers; Animals; Nanoparticles; Drug Delivery Systems; Phytochemicals; Antineoplastic Agents, Phytogenic
PubMed: 38807329
DOI: 10.2174/0113892010242028231002075512 -
International Journal of Molecular... May 2024A novel nanotechnology-based drug delivery system (DDS) targeted at pancreatic cancer cells was developed, characterized, and tested. The system consisted of liposomes...
A novel nanotechnology-based drug delivery system (DDS) targeted at pancreatic cancer cells was developed, characterized, and tested. The system consisted of liposomes as carriers, an anticancer drug (paclitaxel) as a chemotherapeutic agent, and a modified synthetic somatostatin analog, 5-pentacarbonyl-octreotide, a ligand for somatostatin receptor 2 (SSTR2), as a targeting moiety for pancreatic cancer. The cellular internalization, cytotoxicity, and antitumor activity of the DDS were tested in vitro using human pancreatic ductal adenocarcinoma (PDAC) cells with different expressions of the targeted SSTR2 receptors, and in vivo on immunodeficient mice bearing human PDAC xenografts. The targeted drug delivery system containing paclitaxel exhibited significantly enhanced cytotoxicity compared to non-targeted DDS, and this efficacy was directly related to the levels of SSTR2 expression. It was found that octreotide-targeted DDS proved exceptionally effective in suppressing the growth of PDAC tumors. This study underscores the potential of octreotide-targeted liposomal delivery systems to enhance the therapeutic outcomes for PDAC compared with non-targeted liposomal DDS and Paclitaxel-Cremophor EL, suggesting a promising avenue for future cancer therapy innovations.
Topics: Animals; Humans; Pancreatic Neoplasms; Receptors, Somatostatin; Mice; Cell Line, Tumor; Paclitaxel; Liposomes; Drug Delivery Systems; Xenograft Model Antitumor Assays; Octreotide; Somatostatin; Nanotechnology; Antineoplastic Agents; Carcinoma, Pancreatic Ductal
PubMed: 38791582
DOI: 10.3390/ijms25105545 -
Nano Letters Jun 2024Efforts to prolong the blood circulation time and bypass immune clearance play vital roles in improving the therapeutic efficacy of nanoparticles (NPs). Herein, a...
Efforts to prolong the blood circulation time and bypass immune clearance play vital roles in improving the therapeutic efficacy of nanoparticles (NPs). Herein, a multifunctional nanoplatform (BPP@RTL) that precisely targets tumor cells is fabricated by encapsulating ultrasmall phototherapeutic agent black phosphorus quantum dot (BPQD), chemotherapeutic drug paclitaxel (PTX), and immunomodulator PolyMetformin (PM) in hybrid membrane-camouflaged liposomes. Specifically, the hybrid cell membrane coating derived from the fusion of cancer cell membrane and red blood cell membrane displays excellent tumor targeting efficiency and long blood circulation property due to the innate features of both membranes. After collaboration with aPD-L1-based immune checkpoint blockade therapy, a boosted immunotherapeutic effect is obtained due to elevated dendritic cell maturation and T cell activation. Significantly, laser-irradiated BPP@RTL combined with aPD-L1 effectively eliminates primary tumors and inhibits lung metastasis in 4T1 breast tumor model, offering a promising treatment plan to develop personalized antitumor strategy.
Topics: Quantum Dots; Animals; Phosphorus; Immunotherapy; Mice; Paclitaxel; Female; Humans; Cell Line, Tumor; Liposomes; Nanoparticles; Mice, Inbred BALB C
PubMed: 38771956
DOI: 10.1021/acs.nanolett.4c01511 -
Bioorganic Chemistry Jul 2024Camptothecin (CPT), a pentacyclic alkaloid with antitumor properties, is derived from the Camptotheca acuminata. Topotecan and irinotecan (CPT derivatives) were first...
BACKGROUND
Camptothecin (CPT), a pentacyclic alkaloid with antitumor properties, is derived from the Camptotheca acuminata. Topotecan and irinotecan (CPT derivatives) were first approved by the Food and Drug Administration for cancer treatment over 25 years ago and remain key anticancer drugs today. However, their use is often limited by clinical toxicity. Despite extensive development efforts, many of these derivatives have not succeeded clinically, particularly in their effectiveness against pancreatic cancer which remains modest.
AIM OF THE STUDY
This study aimed to evaluate the therapeutic activity of FLQY2, a CPT derivative synthesized in our laboratory, against pancreatic cancer, comparing its efficacy and mechanism of action with those of established clinical drugs.
METHODS
The cytotoxic effects of FLQY2 on cancer cells were assessed using an MTT assay. Patient-derived organoid (PDO) models were employed to compare the sensitivity of FLQY2 to existing clinical drugs across various cancers. The impact of FLQY2 on apoptosis and cell cycle arrest in Mia Paca-2 pancreatic cancer cells was examined through flow cytometry. Transcriptomic and proteomic analyses were conducted to explore the underlying mechanisms of FLQY2's antitumor activity. Western blotting was used to determine the levels of proteins regulated by FLQY2. Additionally, the antitumor efficacy of FLQY2 in vivo was evaluated in a pancreatic cancer xenograft model.
RESULTS
FLQY2 demonstrated (1) potent cytotoxicity; (2) superior tumor-suppressive activity in PDO models compared to current clinical drugs such as gemcitabine, 5-fluorouracil, cisplatin, paclitaxel, ivosidenib, infinitinib, and lenvatinib; (3) significantly greater tumor inhibition than paclitaxel liposomes in a pancreatic cancer xenograft model; (4) robust antitumor effects, closely associated with the inhibition of the TOP I and PDK1/AKT/mTOR signaling pathways. In vitro studies revealed that FLQY2 inhibited cell proliferation, colony formation, induced apoptosis, and caused cell cycle arrest at nanomolar concentrations. Furthermore, the combination of FLQY2 and gemcitabine exhibited significant inhibitory and synergistic effects.
CONCLUSION
The study confirmed the involvement of topoisomerase I and the PDK1/AKT/mTOR pathways in mediating the antitumor activity of FLQY2 in treating Mia Paca-2 pancreatic cancer. Therefore, FLQY2 has potential as a novel therapeutic option for patients with pancreatic cancer.
Topics: Humans; Pancreatic Neoplasms; Camptothecin; Proto-Oncogene Proteins c-akt; TOR Serine-Threonine Kinases; Antineoplastic Agents; Cell Proliferation; Animals; Drug Screening Assays, Antitumor; Mice; Apoptosis; Structure-Activity Relationship; Molecular Structure; Dose-Response Relationship, Drug; Pyruvate Dehydrogenase Acetyl-Transferring Kinase; Mice, Nude; Tumor Cells, Cultured; Cell Line, Tumor
PubMed: 38735265
DOI: 10.1016/j.bioorg.2024.107436 -
ACS Applied Bio Materials May 2024We report an near-infrared (NIR)-trackable and therapeutic liposome with skin tumor specificity. Liposomes with a hydrodynamic diameter of ∼20 nm are tracked under the...
We report an near-infrared (NIR)-trackable and therapeutic liposome with skin tumor specificity. Liposomes with a hydrodynamic diameter of ∼20 nm are tracked under the vein visualization imaging system in the presence of loaded paclitaxel and NIR-active agents. The ability to track liposome nanocarriers is recorded on the tissue-mimicking phantom model and mouse veins after intravenous administration. The trackable liposome delivery provides and photothermal heat (∼40 °C) for NIR-light-triggered area-specific chemotherapeutic release. This approach can be linked with a real-time vein-imaging system to track and apply area-specific local heat, which hitchhikes liposomes from the vein and finally releases them at the tumor site. We conducted studies on mice skin tumors that indicated the disappearance of tumors visibly and histologically (H&E stains). The ability of nanocarriers to monitor after administration is crucial for improving the effectiveness and specificity of cancer therapy, which could be achieved in the trackable delivery system.
Topics: Liposomes; Animals; Infrared Rays; Mice; Skin Neoplasms; Precision Medicine; Paclitaxel; Materials Testing; Biocompatible Materials; Particle Size; Humans; Drug Delivery Systems; Drug Screening Assays, Antitumor
PubMed: 38709861
DOI: 10.1021/acsabm.4c00203 -
Carbohydrate Polymers Jul 2024To alleviate skull defects and enhance the biological activity of taxifolin, this study utilized the thin-film dispersion method to prepare paclitaxel liposomes (TL)....
To alleviate skull defects and enhance the biological activity of taxifolin, this study utilized the thin-film dispersion method to prepare paclitaxel liposomes (TL). Thiolated chitosan (CSSH)-modified TL (CTL) was synthesized through charge interactions. Injectable hydrogels (BLG) were then prepared as hydrogel scaffolds loaded with TAX (TG), TL (TLG), and CTL (CTLG) using a Schiff base reaction involving oxidized dextran and carboxymethyl chitosan. The study investigated the bone reparative properties of CTLG through molecular docking, western blot techniques, and transcriptome analysis. The particle sizes of CTL were measured at 248.90 ± 14.03 nm, respectively, with zeta potentials of +36.68 ± 5.43 mV, respectively. CTLG showed excellent antioxidant capacity in vitro. It also has a good inhibitory effect on Escherichia coli and Staphylococcus aureus, with inhibition rates of 93.88 ± 1.59 % and 88.56 ± 2.83 % respectively. The results of 5-ethynyl-2 '-deoxyuridine staining, alkaline phosphatase staining and alizarin red staining showed that CTLG also had the potential to promote the proliferation and differentiation of mouse embryonic osteoblasts (MC3T3-E1). The study revealed that CTLG enhances the expression of osteogenic proteins by regulating the Wnt signaling pathway, shedding light on the potential application of TAX and bone regeneration mechanisms.
Topics: Animals; Chitosan; Quercetin; Liposomes; Wnt Signaling Pathway; Osteoblasts; Hydrogels; Cell Proliferation; Mice; Skull; Rats; Bone Regeneration; Rats, Sprague-Dawley; Osteogenesis; Staphylococcus aureus; Sulfhydryl Compounds; Anti-Bacterial Agents; Cell Differentiation; Escherichia coli; Male; Molecular Docking Simulation
PubMed: 38670750
DOI: 10.1016/j.carbpol.2024.122115 -
Infection and Drug Resistance 2024Kaposi sarcoma (KS) incidence has decreased since the initiation of combination antiretroviral therapy (cART), but it remains the most common cancer in people with...
INTRODUCTION
Kaposi sarcoma (KS) incidence has decreased since the initiation of combination antiretroviral therapy (cART), but it remains the most common cancer in people with HIV/AIDS (PWHA). PWHA with advanced immunosuppression who initiate antiretroviral therapy are susceptible to the occurrence of an immune reconstitution inflammatory syndrome (IRIS).
CASE PRESENTATION
This report covers the case of a 25-year-old male with AIDS-related KS who relapsed after Liposomal Doxorubicin, but recovered well after administration of nab-paclitaxel (Nab-PTX).
CONCLUSION
This is a rare case in choosing Nab-PTX to treat relapsed AIDS-KS and get good feedback. We report the case to provide a possible solution to treat AIDS-KS.
PubMed: 38623529
DOI: 10.2147/IDR.S456286