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Star-Graft Quarterpolymer-Based Polymersomes as Nanocarriers for Co-Delivery of Hydrophilic/Hydrophobic Chemotherapeutic Agents.

ABSTRACT: We report the fabrication of polymersomes, using as building blocks star-graft quarterpolymers, composed of hydrophobic polystyrene and pH-sensitive poly(2-vinylpyridine)-b-poly(acrylic acid) (P2VP-b-PAA) arms, emanated from a common nodule, enriched by thermosensitive poly(N-isopropylacrylamide) grafts covalently bonded on the PAA block-arms. These multicompartmental polymersomes were evaluated as nanocarriers for the encapsulation and controlled co-delivery of doxorubicin (hydrophilic) and paclitaxel (hydrophobic) chemotherapeutic agents. The polymersomes can load these drugs in different compartments and can efficiently be internalized in the human lung adenocarcinoma epithelial cells, delivering their cargo and inducing high cell apoptosis. The release kinetics of both anticancer agents was controlled differently by the environmental conditions (pH and temperature). Enhanced release was observed at the acidic pH 6.0 and under physiological temperature (37 °C). At the same total drug level, co-delivery of these drugs with the polymersomes caused enhanced cytotoxicity and induced significantly higher cell apoptosis in the cancer cell line compared to the polymersomes loaded with either of the two drugs.

SUBMITTER: Iatridi Z

PROVIDER: S-EPMC6173558 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Star-Graft Quarterpolymer-Based Polymersomes as Nanocarriers for Co-Delivery of Hydrophilic/Hydrophobic Chemotherapeutic Agents.

Iatridi Zacharoula Z Angelopoulou Athina A Voulgari Efstathia E Avgoustakis Konstantinos K Tsitsilianis Constantinos C

ACS omega 20180925 9

We report the fabrication of polymersomes, using as building blocks star-graft quarterpolymers, composed of hydrophobic polystyrene and pH-sensitive poly(2-vinylpyridine)-b-poly(acrylic acid) (P2VP-b-PAA) arms, emanated from a common nodule, enriched by thermosensitive poly(N-isopropylacrylamide) grafts covalently bonded on the PAA block-arms. These multicompartmental polymersomes were evaluated as nanocarriers for the encapsulation and controlled co-delivery of doxorubicin ...[more]

PMID: 30320280

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Project description:Polymersomes are attractive nanocarriers for hydrophilic and lipophilic drugs; they are more stable than liposomes, tunable, and relatively easy to prepare. The copolymer composition and molar mass are critical features that determine the physicochemical properties of the polymersomes including the rate of drug release. We used the triblock-copolymer, poly(2-methyl-2-oxazoline)-block-poly-(dimethysiloxane)-block-poly(2-methyl-2-oxazoline) (PMOXA-PDMS-PMOXA), to form amphipathic polymersomes capable of loading proteins and small hydrophobic agents. The selected agents were unstable neurotrophins (nerve growth factor and brain-derived neurotrophic factor), a large protein CD109, and the fluorescent drug curcumin. We prepared, characterized, and tested polymersomes loaded with selected agents in 2D and 3D biological models. Curcumin-loaded and rhodamine-bound PMOXA-PDMS-PMOXA polymersomes were used to visualize them inside cells. N-Methyl-d-aspartate receptor (NMDAR) agonists and antagonists were also covalently attached to the surface of polymersomes for targeting neurons. Labeled and unlabeled polymersomes with or without loaded agents were characterized using dynamic light scattering (DLS), UV-vis fluorescence spectroscopy, and asymmetrical flow field-flow fractionation (AF4). Polymersomes were imaged and tested for biological activity in human and murine fibroblasts, murine macrophages, primary murine dorsal root ganglia, and murine hippocampal cultures. Polymersomes were rapidly internalized and there was a clear intracellular co-localization of the fluorescent drug (curcumin) with the fluorescent rhodamine-labeled polymersomes. Polymersomes containing CD109, a glycosylphosphatidylinositol-anchored protein, promoted cell migration in the model of wound healing. Nerve growth factor-loaded polymersomes effectively enhanced neurite outgrowth in dissociated and explanted dorsal root ganglia. Brain-derived neurotrophic factor increased dendritic spine density in serum-deprived hippocampal slice cultures. NMDAR agonist- and antagonist-functionalized polymersomes targeted selectively neurons over glial cells in mixed cultures. Collectively, the study reveals the successful incorporation into polymersomes of biologically active trophic factors and small hydrophilic agents that retain their biological activity in vitro, as demonstrated in selected central and peripheral tissue models.

Dataset Information

Star-Graft Quarterpolymer-Based Polymersomes as Nanocarriers for Co-Delivery of Hydrophilic/Hydrophobic Chemotherapeutic Agents.

Publications

Star-Graft Quarterpolymer-Based Polymersomes as Nanocarriers for Co-Delivery of Hydrophilic/Hydrophobic Chemotherapeutic Agents.

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