Preparation of Liposome Gel by Calcium Cross-Linking Induces the Long-Term Release of DOX to Improve the Antitumor Effect.

Doxorubicin (DOX) is one of the most commonly used anticancer drugs; however, its clinical application is greatly limited due to its toxicity and chemotherapy resistance. The delivery of DOX by liposomes (Lipos) can improve the blood circulation time in vivo and reduce toxic side effects, but the drug's accumulation in the tumor is often insufficient for effective treatment. In this study, we present a calcium cross-linked liposome gel for the encapsulation of DOX, demonstrating its superior long-term release capabilities compared to conventional Lipos. By leveraging this enhanced long-term release, we can enhance drug accumulation within tumors, ultimately leading to improved antitumor efficacy. Lipos were prepared using the thin-film dispersion method in this study. We utilized the ion-responsiveness of glutathione-gelatin (GSH-GG) to form the gel outside the Lipos and named the nanoparticles coated with GSH-GG on the outside of Lipos as Lipos@GSH-GG. The average size of Lipos@GSH-GG was around 342.9 nm, with a negative charge of -25.6 mV. The in vitro experiments revealed that Lipos@GSH-GG exhibited excellent biocompatibility and slower drug release compared to conventional Lipos. Further analysis of cellular uptake and cytotoxicity demonstrated that Lipos@GSH-GG loading DOX (DOX&Lipos@GSH-GG) exhibited superior long-term release effects and lower toxic side effects compared to Lipos loading DOX (DOX&Lipos). Additionally, the findings regarding the long-term release effect in vivo and the tumor accumulation within tumor-bearing mice of Lipos@GSH-GG suggested that, compared to Lipos, it demonstrated superior long-term release capabilities and achieved greater drug accumulation within tumors. In vivo antitumor efficacy experiments showed that DOX&Lipos@GSH-GG demonstrated superior antitumor efficacy to DOX&Lipos. Our study highlights Lipos@GSH-GG as a promising nanocarrier with the potential to enhance efficacy and safety by means of long-term release effects and may offer an alternative approach for effective antitumor therapy in the future.

Modulation of Aggregation-Caused Quenching to Aggregation-Induced Emission: Finding a Biocompatible Polymeric Theranostics Platform for Cancer Therapy.

Dual intramolecular FRET polymers are synthesized via Suzuki coupling and their luminescence characteristics from aggregation-caused quenching (ACQ) to aggregation-induced emission (AIE) is modulated conveniently by adjusting the charged ratios. The finally obtained AIE polymer is further employed to construct doxorubicin loaded nanoparticles as a promising theranostics platform for cancer therapy.

Liposome Loaded Ion/Temperature Dual Responsive Gellan Gum Hydrogel as Potential Nasal-To-Brain Delivery System.

Intranasal administration, which can bypass the blood-brain barrier (BBB), is widely recognized as a promising strategy for high-efficiency drug delivery to the brain. Herein, for the purpose of effectively delivering drugs to the brain via intranasal administration, glutathione (GSH)-modified gellan gum (GSH-GG) with ion/temperature dual responsive properties was synthesized and encapsulated on galanthamine hydrobromide (GH)-loaded liposomes (GH-Lipo) for effective GH delivery to the brain (GH-Lipo@GSH-GG). Our results demonstrated that GSH-GG greatly decreased the gelation temperature of GG from 44.0 °C to 22.1 °C without compromising its ion responsiveness. Moreover, GSH-GG had a good protection ability for GH-loaded liposomes without affecting its drug release. Most importantly, the finally obtained GH-Lipo@GSHGG showed acceptable targeted delivery of GH to the brain upon in vivo administration. Therefore, this formulation can be employed as a potential delivery system in nasal-to-brain delivery.

Small Molecule Modifications Significantly Increase the Transfection Efficiency of Low-Molecular Polymer.

Gene vectors with high biocompatibility and transfection efficiency are critical for successful gene therapy. PEI 25K (Polyethyleneimine 25K) is a common polymeric gene vector that has been employed as a positive control material in gene transfection studies due to its good performance in endosome escape. PEI 25K's indegradability and abundance of positive charges, on the other hand, cause toxicity in cells, limiting its use. In this study, we developed the PEI-ER non-viral vector by adding an endoplasmic reticulum (ER) targeting ligand to low molecular weight PEI 1.8K. These small molecule modifications dramatically improved PEI transfection efficiency while barely interfering with compatibility. PEI-ER/DNA complexes were discovered to enter the cell via caveolin-mediated endocytosis, avoiding destruction in the endosome. We believe that this little chemical alteration is a simple solution to enhance the efficacy of cationic polymer vectors in gene transport, and it has a lot of medicinal applications.

Silica-Coated Fe3O4 Nanoparticles as a Bifunctional Agent for Magnetic Resonance Imaging and ZnII Fluorescent Sensing.

Bifunctional magnetic/fluorescent core-shell silica nanospheres (MNPs) encapsulated with the magnetic Fe3O4 core and a derivate of 8-amimoquinoline (N-(quinolin-8-yl)-2-(3-(triethoxysilyl) propylamino) acetamide) (QTEPA) into the shell were synthesized. These functional MNPs were prepared with a modified stöber method and the formed Fe3O4@SiO2-QTEPA core-shell nanocomposites are biocompatible, water-dispersible, and stable. These prepared nanoparticles were characterized by X-ray power diffraction (XRD), transmission electron microscopy (TEM), thermoelectric plasma Quad II inductively coupled plasma mass spectrometry (ICP-MS), superconducting quantum interference device (SQUID), TG/DTA thermal analyzer (TGA) and Fourier transform infrared spectroscopy (FTIR). Further application of the nanoparticles in detecting Zn2+ was confirmed by the fluorescence experiment: the nanosensor shows high selectivity and sensitivity to Zn2+ with a 22-fold fluorescence emission enhancement in the presence of 10 µM Zn2+. Moreover, the transverse relaxivity measurements show that the core-shell MNPs have T2 relaxivity (r2) of 155.05 mM-1 S-1 based on Fe concentration on the 3.0 T scanner, suggesting that the compound can be used as a negative contrast agent for MRI. Further in vivo experiments showed that these MNPs could be used as MRI contrast agent. Therefore, the new nanosensor provides the dual modality of magnetic resonance imaging and optical imaging.

Antibacterial Photodynamic Gold Nanoparticles for Skin Infection.

Damage or injury to the skin creates wounds that are vulnerable to bacterial infection, which in turn retards the process of skin regeneration and wound healing. In patients with severe burns and those with chronic diseases, such as diabetes, skin infection by multidrug-resistant bacteria can be lethal. Therefore, a broad-spectrum therapy to effectively eradicate bacterial infection through a mechanism different from that of antibiotics is much sought after. We successfully synthesized antibacterial photodynamic gold nanoparticles (AP-AuNPs), which are self-assembled nanocomposites of an antibacterial photodynamic peptide and poly(ethylene glycol) (PEG)-stabilized AuNPs. The AP-AuNPs exhibited aqueous and light stability, a satisfactory generation of reactive oxygen species (ROS), and a remarkable antibacterial effect toward both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli upon light irradiation. Moreover, the synthesized nanocomposites significantly inhibited bacterial growth and biofilm formation in vitro. Photodynamic antibacterial treatment accelerated the wound-healing rate in S. aureus infections, mimicking staphylococcal skin infections. Using a combination of the bactericidal effect of a peptide, the photodynamic effect of a photosensitizer, and the multivalency clustering on AuNPs for maximal antibacterial effect under light irradiation, we synthesized AP-AuNPs as a wound-dressing nanomaterial in skin infections to promote wound healing. Our findings indicate a promising strategy in the management of bacterial infections resulting from damaged skin tissue, an aspect that has not been fully explored by our peers.

Intranasal administration of CpG DNA lipoplex prevents pulmonary metastasis in mice.

Synthetic oligodeoxynucleotides containing CpG motifs (CpG DNA) can activate immunocompetent cells which offer the potential advantage of antitumor activity. In this study, we used cationic liposomes to complex with CpG DNA (CpG DNA lipoplex) to prevent pulmonary metastasis following intranasal administration in mice. Intranasal administration of CpG DNA lipoplex prior to challenge with both colon26/Luc and B16F10 cells significantly prevented the proliferation of tumor cells, and the survival time of the mice receiving CpG DNA lipoplex was prolonged. After intranasal administration, [(32)P] CpG DNA lipoplex mainly distributed in nose and lung and induced higher IFN-gamma production in the lung. These results suggest that intranasal administration of CpG DNA lipoplex has a significant effect on preventing pulmonary metastasis in mice.

Mannosylated cationic liposomes/CpG DNA complex for the treatment of hepatic metastasis after intravenous administration in mice.

Immunotherapy using immunostimulatory CpG DNA could be a promising new therapeutic approach to combat refractory hepatic metastasis. In this study, we report the use of a conventional cationic liposomes/CpG DNA complex (Bare/CpG DNA lipoplex) and a mannosylated cationic liposomes/CpG DNA complex (Man/CpG DNA lipoplex) for effective inhibition of hepatic metastasis in mice. After intravenous administration of Bare/CpG DNA lipoplex, higher amounts of IL-12 and IFN-gamma were produced in serum or liver compared with naked CpG DNA, and their production was increased further by Man/CpG DNA lipoplex. Then, Bare/CpG DNA lipoplex and Man/CpG DNA lipoplex were administered intravenously to hepatic metastasis model mice, and the numbers of tumor cells (colon26/Luc) were quantitatively assayed. The number of tumor cells in Man/CpG DNA lipoplex-treated mice was same as those in Bare/CpG DNA lipoplex-treated mice. These results suggest that intravenous administration of not only Bare/CpG DNA lipoplex but also Man/CpG DNA lipoplex could be an efficient immunotherapy for hepatic metastasis.

Efficient peritoneal dissemination treatment obtained by an immunostimulatory phosphorothioate-type CpG DNA/cationic liposome complex in mice.

Peritoneal dissemination remains the most difficult type of metastasis to treat, and current systemic chemotherapy or radiotherapy tends to have little effect; therefore, immunotherapy using immunostimulatory CpG DNA could be a promising new therapeutic approach. Recently, we have reported that intraperitoneal administration of phosphodiester (PO) CpG DNA-lipoplex could efficiently inhibit peritoneal dissemination in mice. In this study, chemically modified phosphorothioate (PS)-CpG DNA and natural PO-CpG DNA were complexed with DOTMA/cholesterol cationic liposomes (PS-CpG DNA-lipoplex and PO-CpG DNA-lipoplex) and their antitumor activity was evaluated in a mouse model of peritoneal dissemination. Intraperitoneal administration of the PS-CpG DNA-lipoplex inhibited the proliferation of tumor cells in the greater omentum and the mesentery more efficiently than PO-CpG DNA-lipoplex. PS-CpG DNA-lipoplex induced higher cytokine production from primary cultured mouse peritoneal macrophages, suggesting that the high antitumor activity of the PS-CpG DNA-lipoplex is mediated by a high rate of cytokine production from immunocompetent cells such as macrophages. The serum transaminase levels of mice receiving intraperitoneal PS-CpG DNA-lipoplex treatment were measured to evaluate systemic toxicity, and these were found to be the same as those of untreated mice. These results suggest that intraperitoneal administration of PS-CpG DNA-lipoplex could be efficient immunotherapy for peritoneal dissemination.