Dataset Information

"Navigate-dock-activate" anti-tumor strategy: Tumor micromilieu charge-switchable, hierarchically activated nanoplatform with ultrarapid tumor-tropic accumulation for trackable photothermal/chemotherapy.

ABSTRACT: The delivery of therapeutics into tumors remains a challenge in nanoparticle-mediated drug delivery. However, effective therapies such as photothermal therapy (PTT) are limited by quick systemic clearance and non-specific biodistribution. Anti-tumor strategies tailored to accommodate both tumor accumulation/retention and cellular internalization under a single platform would be a promising strategy. This work demonstrates a hierarchical activating strategy that would exhibit enhanced circulation and rapid tumor-tropism as well as facilitate tumor penetration, followed by tumor-specific drug release to realize trackable photothermal/chemotherapy. Methods: We engineered a lithocholic acid-conjugated disulfide-linked polyethyleneimine micelle (LAPMi) loaded with paclitaxel (LAPMi-PTX, L), followed by the electrostatic adsorption of indocyanine green (ICG, I) on LAPMI-PTX and subsequently coated them with thermosensitive DPPC and DSPE-PEG-NH₂ lipids (L), producing Lipid/ICG/LAPMi-PTX (LIL-PTX) nanoparticles (NPs). The characteristics of NPs, including physicochemical characterization, photothermal & pH responsiveness, cell uptake, tumor spheroid penetration, anti-tumor efficacy and hierarchical activation of LIL-PTX NPs were investigated in vitro and in vivo by using CT26 cell line. The anti-metastatic potential of LIL-PTX NPs were demonstrated using 4T1 orthotopic tumor model. Results: The NPs synthesized possessed charge switchability in the mildly acidic pH, and were laser- and pH-responsive. Dual stimuli-responsive nature of LIL-PTX NPs improved the disposition of therapeutics to the tumor, reflected by enhanced intracellular uptake, tumor spheroid penetration and in vitro cytotoxicity studies. LIL-PTX NPs readily switched its surface charge from neutral to positive upon reaching the tumor milieu, thus resulting in rapid tumor tropism and accumulation. Under near-infrared laser irradiation, the thermosensitive lipids on LIL-PTX NPs were deshielded, and the tumor-penetrating LAPMi-PTX was subsequently exposed to the tumor milieu, thus resulting in enhanced intracellular internalization. Next, LAPMi-PTX evaded the endo-lysosomes, thereby releasing the PTX through the degradation of LAPMi mediated by intracellular GSH in the tumor. LIL-PTX NPs significantly improved the therapy by eradicating primary tumors completely and suppressing their subsequent lung metastasis. Conclusion: The improved therapeutic index is due to enhanced passive targeting by rapid tumor-tropic accumulation and tumor penetration by laser-driven exposure of LAPMi, thereby improving the therapeutic delivery for image-guided photothermal/chemotherapy.

SUBMITTER: Cherukula K

PROVIDER: S-EPMC6525992 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundFunctional annotation of genes is an essential step in omics data analysis. Multiple databases and methods are currently available to summarize the functions of sets of genes into higher level representations, such as ontologies and molecular pathways. Annotating results from omics experiments into functional categories is essential not only to understand the underlying regulatory dynamics but also to compare multiple experimental conditions at a higher level of abstraction. Several tools are already available to the community to represent and compare functional profiles of omics experiments. However, when the number of experiments and/or enriched functional terms is high, it becomes difficult to interpret the results even when graphically represented. Therefore, there is currently a need for interactive and user-friendly tools to graphically navigate and further summarize annotations in order to facilitate results interpretation also when the dimensionality is high.ResultsWe developed an approach that exploits the intrinsic hierarchical structure of several functional annotations to summarize the results obtained through enrichment analyses to higher levels of interpretation and to map gene related information at each summarized level. We built a user-friendly graphical interface that allows to visualize the functional annotations of one or multiple experiments at once. The tool is implemented as a R-Shiny application called FunMappOne and is available at https://github.com/grecolab/FunMappOne .ConclusionFunMappOne is a R-shiny graphical tool that takes in input multiple lists of human or mouse genes, optionally along with their related modification magnitudes, computes the enriched annotations from Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, or Reactome databases, and reports interactive maps of functional terms and pathways organized in rational groups. FunMappOne allows a fast and convenient comparison of multiple experiments and an easy way to interpret results.

Project description:The subpopulations of mesenchymal stem cells isolated from breast adipose tissue which display migrated towards conditioned media from MDA-MB231 cell line were expanded for miRNA analysis. The tumor microenvironment (TM) is known to promote tumor growth and progression. Ubiquitously distributed tissue resident stem cells (MSCs) elicit regenerative properties. In addition, they are capable of homing to sites of inflammation, injury, and tumor. Considering the tumor tropic property of MSCs, the interaction between the breast cancer (BC) microenvironment and breast resident adipose tissue derived MSCs (ASCs) merits further investigations. Initial data indicate that a subset of ASCs derived from breast adipose tissue (B-ASCs) display a high affinity towards the conditioned media (CM) from two breast cancer cell lines, MDA-MB231 (MDA-CM) and MCF7 (MCF-CM). Profiling secreted cytokines of these CMs identified significant expression of angiogenin, GM-CSF, and IL-6. While the expression of GRO-α, MCP-1, RANTES, and IL-1α is more pronounced in MDA-CM, MCF-CM contains higher amounts of IGFBP2, TRAIL, and ErbB3. Gene expression profiling suggests that despite the distinct differences, both migratory subset of B-ASCs towards MDA-CM and MCF-CM display perturbed expression of genes like KISS1, TNSF1, IL18 and MMP2, which could be associated with a defensive role of B-ASCs. In addition, the BC microenvironment alters microRNA (miRNA) expressions in B-ASCs. in this study the migratory cells were evaluated for miRNA expression versus non-migratory counterparts. as controls unexposed parental cell lines (2) were used on the same hybridization chip in which one labeled Hy3 and other labeled Hy5. The ratio of the control parental cells was used as base nanalysis of miRNA expression in MSCs. we also include another control in this study, the migratory subpopulations of MSCs which display migratory potentials against protein gradient (M5) were analyzed for miRNA expression versus non-migratory counterparts (NM-5). using this control facilitate identification of those miRNA responsive to tumor CM. the data analysis confirm that altered gene and miRNA profiles resulted from exposure of MCF-CM and MDA-CM on B-ASCs are similar to those observed in B-ASCs isolated from breast adipose tissue of BC patients. Analysis the signaling between the B-ASCs and TM may help in understanding the possible role of B-ASCs in stasis, progression, or regression of the BC. The microRNA expression of migratory subpopulations were compared to parental populations of MSCs.

Project description:The subpopulations of mesenchymal stem cells isolated from breast adipose tissue which display migrated towards conditioned media from MDA-MB231 cell line were expanded for miRNA analysis. The tumor microenvironment (TM) is known to promote tumor growth and progression. Ubiquitously distributed tissue resident stem cells (MSCs) elicit regenerative properties. In addition, they are capable of homing to sites of inflammation, injury, and tumor. Considering the tumor tropic property of MSCs, the interaction between the breast cancer (BC) microenvironment and breast resident adipose tissue derived MSCs (ASCs) merits further investigations. Initial data indicate that a subset of ASCs derived from breast adipose tissue (B-ASCs) display a high affinity towards the conditioned media (CM) from two breast cancer cell lines, MDA-MB231 (MDA-CM) and MCF7 (MCF-CM). Profiling secreted cytokines of these CMs identified significant expression of angiogenin, GM-CSF, and IL-6. While the expression of GRO-M-NM-1, MCP-1, RANTES, and IL-1M-NM-1 is more pronounced in MDA-CM, MCF-CM contains higher amounts of IGFBP2, TRAIL, and ErbB3. Gene expression profiling suggests that despite the distinct differences, both migratory subset of B-ASCs towards MDA-CM and MCF-CM display perturbed expression of genes like KISS1, TNSF1, IL18 and MMP2, which could be associated with a defensive role of B-ASCs. In addition, the BC microenvironment alters microRNA (miRNA) expressions in B-ASCs. in this study the migratory cells were evaluated for miRNA expression versus non-migratory counterparts. as controls unexposed parental cell lines (2) were used on the same hybridization chip in which one labeled Hy3 and other labeled Hy5. The ratio of the control parental cells was used as base nanalysis of miRNA expression in MSCs. we also include another control in this study, the migratory subpopulations of MSCs which display migratory potentials against protein gradient (M5) were analyzed for miRNA expression versus non-migratory counterparts (NM-5). using this control facilitate identification of those miRNA responsive to tumor CM. the data analysis confirm that altered gene and miRNA profiles resulted from exposure of MCF-CM and MDA-CM on B-ASCs are similar to those observed in B-ASCs isolated from breast adipose tissue of BC patients. Analysis the signaling between the B-ASCs and TM may help in understanding the possible role of B-ASCs in stasis, progression, or regression of the BC. The microRNA expression of migratory subpopulations were compared to parental populations of MSCs.

Dataset Information

"Navigate-dock-activate" anti-tumor strategy: Tumor micromilieu charge-switchable, hierarchically activated nanoplatform with ultrarapid tumor-tropic accumulation for trackable photothermal/chemotherapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets