Dextran derivative-based pH-sensitive liposomes for cancer immunotherapy

Abstract

pH-Sensitive dextran derivatives having 3-methylglutarylated residues (MGlu-Dex) were prepared by reacting dextran with 3-methyl-glutaric anhydride. MGlu-Dex changed the protonation state and their characteristics from hydrophilic to hydrophobic in neutral and acidic pH regions. Surface modification of egg yolk phosphatidylcholine liposomes with MGlu-Dex produced highly pH-sensitive liposomes that were stable at neutral pH but which were destabilized strongly in the weakly acidic pH region. MGlu-Dex-modified liposomes were taken up efficiently by dendritic cells and delivered entrapped ovalbumin (OVA) molecules into the cytosol. When MGlu-Dex-modified liposomes loaded with OVA were administered subcutaneously to mice, the antigen-specific humoral and cellular immunity was induced more effectively than the unmodified liposomes loaded with OVA. Furthermore, administration of MGlu-Dex-modified liposomes loaded with OVA to mice bearing E.G7-OVA tumor significantly suppressed tumor growth and extended the mice survival. Results suggest that MGlu-Dex-modified liposomes are promising for the production of safe and potent antigen delivery systems that contribute to the establishment of efficient cancer immunotherapy.

Using hyaluronic acid-functionalized pH stimuli-responsive mesoporous silica nanoparticles for targeted delivery to CD44-overexpressing cancer cells

“…Many methods have been developed to synthesize pH-responsive MSNs systems and pH-sensitive lipid membrane as drug carriers to deliver drugs and trigger the release of encapsulated drugs in tumor cells, an important role in all drug delivery systems. [14][15][16][17] The pH-sensitive lipid membrane that target tumors are stable at physiological pH values, but are designed to become unstable under acidic conditions, resulting in the release of their drug cargo. 18 Some studies have shown that coated nanoparticles of pH-sensitive lipid membrane can protect the drug and increase the drug concentration, which is favored to decrease systemic toxicity and enhance antitumor activity.…”

The antitumor activity of tumor-homing peptide-modified thermosensitive liposomes containing doxorubicin on MCF-7/ADR: in vitro and in vivo

“…11 In fact, the ability to control and produce a burst release of the encapsulated drug from liposomes would be extremely advantageous and may prove to be an essential step in providing effective levels of drug in the tumor. 12 Several approaches for triggered drug release from liposomes have been investigated, such as enzyme-activated, 13,14 pH-sensitive, 15,16 lightsensitive, 17,18 ultrasound-triggered, [19][20][21] and thermosensitive liposomes. [22][23][24][25][26][27][28][29][30] Thermosensitive liposomes can be prepared from phospholipids that exhibit a sharp gel-to-liquid crystalline transition.…”

Liposomal Nanoformulations as Current Tumor-Targeting Approach to Cancer Therapy

“…Surface modification of phosphatidylcholine liposomes with MGlu-Dex enabled obtaining highly pH-sensitive liposomes that were stable at neutral pH but were strongly destabilized in the weakly acidic pH region (pH ~5.5). In vivo data suggested that compared to unmodified liposomes, MGlu-Dex-ovalbumin liposomes efficiently increased the uptake of ovalbumin by dendritic cells and significantly suppressed tumor growth [58].…”