Enhancement of radiotherapy efficacy by pleiotropic liposomes encapsulated paclitaxel and perfluorotributylamine.
Ontology highlight
ABSTRACT:
SUBMITTER: Jiang X
PROVIDER: S-EPMC8241066 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundPhotodynamic 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.MethodsThe 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.ResultsIn 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.ConclusionThe PDT therapy with ICG-Lipo-PTX may be an effective treatment for breast cancer.
| S-EPMC10955121 | biostudies-literature
Project description:Introduction:Pancreatic cancer, or pancreatic duct adenocarcinoma (PDAC), remains one of the most lethal cancers and features insidious onset, highly aggressive behavior and early distant metastasis. The dense fibrotic stroma surrounding tumor cells is thought to be a shield to resist the permeation of chemotherapy drugs in the treatment of PDAC. Thus, we synthesized a pancreas-targeting paclitaxel-loaded PEGylated liposome and investigated its antitumor efficacy in the patient-derived orthotopic xenograft (PDOX) nude mouse models of PDAC. Methods:The PTX-loaded PEGylated liposomes were prepared by film dispersion-ultrasonic method and modified by an N,N-dimethyl tertiary amino residue. Morphology characteristics of the PTX-loaded liposomes were observed by transmission electron microscope (TEM). The PDOX models of PDAC were established by orthotopic implantation and imaged by a micro positron emission tomography/computed tomography (PET/CT) imaging system. The in vivo distribution and antitumor study were then carried out to observe the pancreas-targeting accumulation and the antitumor efficacy of the proposed PTX liposomes. Results:PTX loaded well into both modified (PTX-Lip2N) and unmodified (PTX-Lip) PEGylated liposomes with spherical shapes and suitable parameters for the endocytosis process. The PDOX nude mouse models were successfully created in which high 18F-FDG intaking regions were observed by micro-PET/CT. In addition to higher cellular uptakes of PTX-Lip2N by the BxPC-3 cells, the proposed nanoparticle had a notable penetrating ability towards PDAC tumor tissues, and consequently, the antitumor ability of PTX-Lip2N was significantly superior to the unmodified PTX-Lip in vivo PDOX models and even more effective than nab-PTX in restraining tumor growth. Conclusion:The modified pancreas-targeting PTX-loaded PEGylated liposomes provide a promising platform for the treatment of pancreatic cancer.
| S-EPMC7398872 | biostudies-literature
Project description:Paclitaxel (PTX)-loaded liposomes were developed with the goal of enhancing the effects of cancer treatment. Although loading substances into the lipid membrane of liposome cause some destabilization of the lipid membrane, PTX was nearly exclusively embedded in the lipid membrane of liposomes, due to its low water solubility. Hydrophobic drugs can be encapsulated into the inner core of bovine serum albumin (BSA)-encapsulated liposomes (BSA-liposome) via noncovalent binding to albumin. Since PTX is able to noncovalently bind to albumin, we attempted to prepare PTX-loaded BSA-liposome (PTX-BSA-liposome). The amount of PTX loaded in the BSA-liposome could be increased substantially by using ethanol, since ethanol increases PTX solubility in BSA solutions via prompting the binding PTX to BSA. On the basis of the results of transmission electron microscopy and small-angle X-ray scattering, PTX-BSA-liposome formed unilamellar vesicles that were spherical in shape and the PTX was encapsulated into the inner aqueous core of the liposome as a form of PTX-BSA complex. In addition, the PTX-BSA-liposome, as well as nab-PTX, showed cytotoxicity against human pancreatic cancer cells, AsPC-1 cells, in a PTX concentration-dependent manner. The in vivo antitumor effect of PTX-BSA-liposomes was also observed in a mouse model that had been subcutaneously inoculated with pancreatic cancer cells by virtue of its high accumulation at the tumor site via the enhanced permeability retention effect. These results suggest that PTX-BSA-liposomes have the potential for serving as a novel PTX preparation method for the treatment of pancreatic cancer.
| S-EPMC6649292 | biostudies-literature
Project description:Multidrug resistance (MDR) is a major impediment to cancer treatment. A promising strategy for treating MDR is the joint delivery of combined anticancer agents to tumor cells in a single nanocarrier. Here, for the first time, Resveratrol (Res) was co-encapsulated with paclitaxel (PTX) in a PEGylated liposome to construct a carrier-delivered form of combination therapy for drug-resistant tumors. The composite liposome had an average diameter of 50 nm with encapsulated efficiencies of above 50%. The studies demonstrated that the composite liposome could generate potent cytotoxicity against the drug-resistant MCF-7/Adr tumor cells in vitro and enhance the bioavailability and the tumor-retention of the drugs in vivo. Moreover, systemic therapy with the composite liposome effectively inhibited drug-resistant tumor in mice (p < 0.01), without any notable increase in the toxicity. These results suggested that the co-delivery of Res and a cytotoxic agent in a nanocarrier may potentially improve the treatment of drug-resistant tumors.
| S-EPMC4780086 | biostudies-other
Project description:Mitochondria serve as both "energy factories" and "suicide weapon stores" of cells. Targeted delivery of cytotoxic drugs to the mitochondria of tumor cells and tumor vascular cells is a promising strategy to improve the efficacy of chemotherapy. Here, multistage tumor-targeting liposomes containing two targeted peptide-modified lipids, cRGD-PEG2000-DSPE and KLA-PEG2000-DSPE, were developed for encapsulation of the anticancer drug paclitaxel (PTX, RGD-KLA/PTX-Lips). Compared with Taxol (free PTX), RGD/PTX-Lips and KLA/PTX-Lips, the half-maximal inhibitory concentration (IC50) value of RGD-KLA/PTX-Lips in vitro was 1.9-, 36.7- and 22.7-fold lower with 4T1 cells, respectively, because of higher levels of cellular uptake. Similar results were also observed with human umbilical vascular endothelial cells (HUVECs). An apoptosis assay showed that the total apoptotic ratio of RGD-KLA/PTX-Lips was the highest because of the mitochondria-targeted drug delivery and the activation of mitochondrial apoptosis pathways, as evidenced by visible mitochondrial localization, decreased mitochondrial membrane potential, release of cytochrome c and increased activities of caspase-9 and caspase-3. The strongest tumor growth inhibition (TGI; 80.6%) and antiangiogenesis effects without systemic toxicity were also observed in RGD-KLA/PTX-Lip-treated 4T1 tumor xenograft BALB/c mice. In conclusion, these multistage tumor-targeting liposomes represent a promising anticancer drug delivery system (DDS) capable of maximizing anticancer therapeutic efficacy and minimizing systemic toxicity.
| S-EPMC5338999 | biostudies-literature
Project description:It has been predicted that nonameric peptides I (VP1(26-34), RRQHTDVSF), II (VP1(157-165), RTLPTSFNY) and III (VP1(45-53), KEQVNVLDL) from the VP1 capsid protein of the foot-and-mouth disease virus (FMDV) are T cell epitopes. To investigate whether these peptides have immunological activity, BALB/c mice were immunized with peptide I, II or III conjugated with immunostimulating complexes (ISCOMs). A cytotoxic T lymphocyte assay was used to evaluate the cytotoxic activity induced by peptides along with by measuring peptide-specific T-cell proliferation and CD8(+) T lymphocyte numbers in whole blood and interferon (IFN)-? production in peripheral blood mononuclear cells induced by peptides. To further identify the protective efficacy of peptides, an FMDV challenge assay was done in guinea pigs. Peptides I and II stimulated significant increases in T-cell proliferation, CD8(+) T lymphocytes, and IFN-? secretion and cytotoxic activity compared to controls. The FMDV challenge assay indicated peptides I and II can protect over 60% of animals from virus attack. The results demonstrate that peptides I and II encapsulated in liposomes should be CTL epitopes of FMDV and can protect animals from virus attack to some extent.
| S-EPMC3706604 | biostudies-literature
Project description:To date, numerous analytical methods have been developed to monitor phospholipase A2 (PLA2) activity. However, many of these methods require the use of unnatural PLA2 substrates that may alter enzyme kinetics, and probes that cannot be extended to applications in more complex environments. It would be desirable to develop a versatile assay that monitors PLA2 activity based on interactions with natural phospholipids in complex biological samples. Here, we developed an activatable T1 magnetic resonance (MR) imaging contrast agent to monitor PLA2 activity. Specifically, the clinically approved gadolinium (Gd)-based MR contrast agent, gadoteridol, was encapsulated within nanometer-sized phospholipid liposomes. The encapsulated Gd exhibited a low T1-weighted signal, due to low membrane permeability. However, when the phospholipids within the liposomal membrane were hydrolyzed by PLA2, encapsulated Gd was released into bulk solution, resulting in a measureable change in the T1-relaxation time. These activatable MR contrast agents can potentially be used as nanosensors for monitoring of PLA2 activity in biological samples with minimal sample preparation.
| S-EPMC4223643 | biostudies-other
Project description:Nanoencapsulation has emerged as a novel strategy to enhance the pharmacokinetic and therapeutic potential of conventional drugs. Recent studies from our lab have established the efficacy of curcumin in sensitizing cervical cancer cells and breast cancer cells towards paclitaxel and 5-FU chemotherapy respectively. Factors that hinder the clinical use of curcumin as a sensitizer or therapeutic agent include its poor bioavailability and retention time. Earlier reports of improvement in bioavailability and retention of drugs upon nanoencapsulation have motivated us in developing various nanoformulations of curcumin, which were found to exhibit significant enhancement in bioavailability and retention time as assessed by our previous in vitro studies. Among the various formulations tested, curcumin-entrapped in PLGA-PEG nanoparticles conjugated to folic acid (PPF-curcumin) displayed maximum cell death. In the present study, we have demonstrated the efficacy of this formulation in augmenting the bioavailability and retention time of curcumin, in vivo, in Swiss albino mice. Further, the acute and chronic toxicity studies proved that the formulation is pharmacologically safe. We have also evaluated its potential in chemosensitizing cervical cancer cells to paclitaxel and have verified the results using cervical cancer xenograft model in NOD-SCID mice. Folic acid conjugation significantly enhanced the efficacy of curcumin in down-regulating various survival signals induced by paclitaxel in cervical cancer cells and have considerably improved its potential in inhibiting the tumor growth of cervical cancer xenografts. The non-toxic nature coupled with improved chemosensitization potential makes PPF-curcumin a promising candidate formulation for clinical trials.
| S-EPMC5746074 | biostudies-literature
Project description:Few endocytosed ligands, including bacterial toxins and simian virus 40 (SV40) have been shown to reach the endoplasmic reticulum (ER) in mammalian cells. Using calcein and fluorescently labelled lactoferrin encapsulated in fusogenic liposomes we found that the cargo uses a microtubule-based pathway with ER delivery. Endocytic uptake of the lipid vesicles was cholesterol dependent in all cell lines tested, including the caveolin-1-deficient human hepatoma 7 cell line. The ligand was transported in non-caveosome organelles requiring acidic pH for maturation, but able to escape the lysosomal route. These organelles were not recycling endosomes either, as shown by the lack of co-localization with recycling transferrin. Co-localization with the ER-tracker, orange fluorescent protein with KDEL signal retention and cholera toxin in live microscopy revealed an ER distribution of the fluorescent ligand. Brefeldin A, which prevents Golgi-dependent retrograde trafficking, does not disrupt the cargo delivery to the ER. This new endocytic pathway making use of acidic endosome-like organelles is an alternative to the reported SV40 caveolae pathways. Exploiting a cellular route linking the cell surface to the ER, fusogenic liposomes may become efficient drug delivery vehicles for ER stress and diseases.
| S-EPMC4516470 | biostudies-literature
Project description:Stealth liposomes can be used to extend the blood circulation time of encapsulated therapeutics. Inclusion of 2 molar % porphyrin-phospholipid (PoP) imparted optimal near infrared (NIR) light-triggered release of doxorubicin (Dox) from conventional sterically stabilized stealth liposomes. The type and amount of PoP affected drug loading, serum stability and drug release induced by NIR light. Cholesterol and PEGylation were required for Dox loading, but slowed light-triggered release. Dox in stealth PoP liposomes had a long circulation half-life in mice of 21.9 h and was stable in storage for months. Following intravenous injection and NIR irradiation, Dox deposition increased ∼ 7 fold in treated subcutaneous human pancreatic xenografts. Phototreatment induced mild tumor heating and complex tumor hemodynamics. A single chemophototherapy treatment with Dox-loaded stealth PoP liposomes (at 5-7 mg/kg Dox) eradicated tumors while corresponding chemo- or photodynamic therapies were ineffective. A low dose 3 mg/kg Dox phototreatment with stealth PoP liposomes was more effective than a maximum tolerated dose of free (7 mg/kg) or conventional long-circulating liposomal Dox (21 mg/kg). To our knowledge, Dox-loaded stealth PoP liposomes represent the first reported long-circulating nanoparticle capable of light-triggered drug release.
| S-EPMC4644481 | biostudies-literature