Enhancing the Anticancer Activity of Attenuated by Cell Wall Functionalization with "Clickable" Doxorubicin.

Among bacteria used as anticancer vaccines, attenuated (Lm) stands out, because it spreads from one infected cancer cell to the next, induces a strong adaptive immune response, and is suitable for repeated injection cycles. Here, we use click chemistry to functionalize the Lm cell wall and turn the bacterium into an "intelligent carrier" of the chemotherapeutic drug doxorubicin. Doxorubicin-loaded Lm retains most of its biological properties and, compared to the control fluorophore-functionalized bacteria, shows enhanced cytotoxicity against melanoma cells both in vitro and in a xenograft model in zebrafish.

Fluorescence lifetime microscopy unveils the supramolecular organization of liposomal Doxorubicin.

The supramolecular organization of Doxorubicin (DOX) within the standard Doxoves® liposomal formulation (DOX®) is investigated using visible light and phasor approach to fluorescence lifetime imaging (phasor-FLIM). First, the phasor-FLIM signature of DOX® is resolved into the contribution of three co-existing fluorescent species, each with its characteristic mono-exponential lifetime, namely: crystallized DOX (DOX, 0.2 ns), free DOX (DOX, 1.

Mechanistic Insights into the Release of Doxorubicin from Graphene Oxide in Cancer Cells.

Liposomal doxorubicin (L-DOX) is a popular drug formulation for the treatment of several cancer types (e.g., recurrent ovarian cancer, metastatic breast cancer, multiple myeloma, etc.

A Gemini Cationic Lipid with Histidine Residues as a Novel Lipid-Based Gene Nanocarrier: A Biophysical and Biochemical Study.

This work reports the synthesis of a novel gemini cationic lipid that incorporates two histidine-type head groups (C₃(CHis)₂). Mixed with a helper lipid 1,2-dioleoyl--glycero-3-phosphatidyl ethanol amine (DOPE), it was used to transfect three different types of plasmid DNA: one encoding the green fluorescence protein (pEGFP-C3), one encoding a luciferase (pCMV-Luc), and a therapeutic anti-tumoral agent encoding interleukin-12 (pCMV-IL12). Complementary biophysical experiments (zeta potential, gel electrophoresis, small-angle X-ray scattering (SAXS), and fluorescence anisotropy) and biological studies (FACS, luminometry, and cytotoxicity) of these C₃(CHis)₂/DOPE-pDNA lipoplexes provided vast insight into their outcomes as gene carriers.

Human Biomolecular Corona of Liposomal Doxorubicin: The Overlooked Factor in Anticancer Drug Delivery.

More than 20 years after its approval by the Food and Drug Administration (FDA), liposomal doxorubicin (DOX) is still the drug of choice for the treatment of breast cancer and other conditions such as ovarian cancer and multiple myeloma. Yet, despite the efforts, liposomal DOX did not satisfy expectations at the clinical level. When liposomal drugs enter a physiological environment, their surface gets coated by a dynamic biomolecular corona (BC).

Dynamic fingerprinting of sub-cellular nanostructures by image mean square displacement analysis.

Here we provide demonstration that image mean square displacement (iMSD) analysis is a fast and robust platform to address living matter dynamic organization at the level of sub-cellular nanostructures (e.g. endocytic vesicles, early/late endosomes, lysosomes), with no a-priori knowledge of the system, and no need to extract single trajectories.