How can liposomes be actively targeted for the treatment of cancer?
■ Liposomes can be actively targeted by modifying the liposomal surface with various ligands that interact with overexpressed cancer cell surface receptors, or receptors and antigens present in the tumor microenvironment.
How can liposomes be surface modified to improve their function?
Liposomes can be surface modified by various strategies to endow them with multiple functionalities, including long systemic circulation, increased accumulation at the target tissue, increased cellular internalization and organelle-specific drug delivery [ 3 ]. Hydrophilic and hydrophobic drugs encapsulated within a PEGylated liposome.
Can liposomes be used to deliver radionuclides?
Here, PEG-stabilized liposomes loaded with a unique DNA-intercalating compound were targeted to tumor cells to promote the delivery of radionuclides to DNA. This system has proven beneficial in eliminating tumor cells with minimum off-target effects.
Does Liposome Technology Enhance immunostimulatory therapies?
These studies suggest that immunostimulatory therapies via liposomes can induce potent anti-tumor effects while eliminating systemic side effects, which can efficiently broaden the clinical application of immunostimulatory therapies by using liposome technology.
How do you prepare liposomes?
All the methods of preparing the liposomes involve four basic stages:Drying down lipids from organic solvent.Dispersing the lipid in aqueous media.Purifying the resultant liposome.Analyzing the final product.
How are liposomes used in cancer treatment?
Liposomes can actively target tumour tissues using the antibody-based approach. This can be done by adding certain antibodies to the liposomal surface—so called immunoliposomes (ILP)—which are specific to the cancer cells or to the endothelial cells of the tumour vasculature [58].
How are liposomes used in medical therapies?
Liposomes have been used to deliver anticancer agents in order to reduce the toxic effects of the drugs when given alone or to increase the circulation time and effectiveness of the drugs.
How are liposomes administered?
Liposome-entrapped drugs are distributed within the body much differently than free drugs; when administered intravenously to healthy animals and humans, most of the injected vesicles accumulate in the liver, spleen, lungs, bone marrow, and lymph nodes.
Which of the following is an example of liposomes for cancer therapy?
Doxil(tm), liposomal doxorubicin, is the ideal example of the active loading by pH gradient method (Lasic et al. 1992. Gelation of liposome interior. A novel method for drug encapsulation.
What is liposomal chemotherapy?
Liposomal doxorubicin is a chemotherapy drug that is also called by the brand names Caelyx or Myocet. It contains the chemotherapy drug doxorubicin (Adriamycin) wrapped up in a fatty covering called a liposome. It is a treatment for some types of cancer, including: breast cancer. ovarian cancer.
What is liposomal formulation?
A liposome drug formulation is different from (1) an emulsion, which is a dispersed system of oil in water, or water in oil phases containing one or more surfactants, (2) a microemulsion, which is a thermodynamically stable two phase system containing oil or lipid, water and surfactants, and (3) a drug-lipid complex.
How are liposomes commercially used?
The industrial applications include the use of liposomes as drug delivery vehicles in medicine, adjuvants in vaccination, signal enhancers/carriers in medical diagnostics and analytical biochemistry, solubilizers for various ingredients as well as support matrices for various ingredients and penetration enhancers in ...
How are liposomes used for drug delivery?
Liposomes protect some drugs against chemical and immunological breakdown, as well as protecting them against the effect of enzymes. Liposomes give lowered toxicity and lower dosing because of sustained drug levels, especially when so called “stealth” liposomes are used [38].
What is liposome injection?
Collapse Section. Amphotericin B liposomal injection is used to treat fungal infections such as cryptococcal meningitis (a fungal infection of the lining of the spinal cord and brain) and visceral leishmaniasis (a parasitic disease that usually affects spleen, liver, and bone marrow) in certain people.
What are liposomes made of?
Liposomes are spherical vesicles made up of biodegradable natural or synthetic phospholipids. They usually have one or more concentric membranes. Liposomes are composed of phospholipids, which are amphipathic and are characterized by having a lipophilic tail and hydrophilic head on the same molecule (Lasic, 1993).
How to ensure quality of liposome drug products?
In order to ensure the quality of liposome drug products, not only the intermediate control and process control should be implemented in the production process, the quality of the final product should be tested, but also the appropriate control strategy should be formulated based on the understanding of the production process.
What is the purpose of liposome preparation?
The main purpose of ideal liposome preparation is to obtain high drug entrapment efficiency, narrow particle size distribution and long-term stability of liposome products. Therefore, generally speaking, the following aspects are involved in the design and preparation of liposomes:
What are liposomes made of?
Liposomes are small spherical vesicles composed of one or more lipid bilayers with an aqueous core. The preparation process can be divided into the following three basic steps:
How are lipids dispersed in the aqueous medium?
When the lipid is dispersed in the aqueous medium by stirring, the formation of population vesicles may reach the size range. Liposomes can be prepared by mechanical methods, solvent dispersion methods and methods based on fusion or size conversion.
Why are liposomes important?
As a kind of artificially prepared vesicles, liposomes have become an important tool to improve the release of antibiotics, anticancer drugs, antifungal drugs , peptide hormones, enzymes, vaccines, and genetic materials. Due to different preparation methods and lipid composition, liposomes can be classified according to their lamellarity, particle size, charge, and application. Regardless of their solubility, the flexibility of their behavior can be utilized through different routes of administration.
What are the aspects of quality control of liposomes?
The quality control of liposomes is mainly evaluated from the aspects of particle size distribution, average particle size, surface morphology, entrapment efficiency, drug loading, stability, oxidation degree of phospholipids, phase transition temperature, residual amount of organic solvent and sterilization effect.
Is liposome emulsion good for storage?
In practical application, emulsion is the main dosage form of liposome, but the long-term stability of this dosage form is poor, so it is not suitable for long-term storage. Lyophilization of liposomes into solid dosage forms provides the possibility of simple administration and shows higher storage stability than other dosage forms.
How do liposomes help cancer?
Nanocarriers, such as liposomes, have favorable advantages with the potential to further improve cancer immunotherapy and even stronger immune responses by improving cell type-specific delivery and enhancing drug efficacy. Liposomes can offer solutions to common problems faced by several cancer immunotherapies, including the following: (1) Vaccination: Liposomes can improve the delivery of antigens and other stimulatory molecules to antigen-presenting cells or T cells; (2) Tumor normalization: Liposomes can deliver drugs selectively to the tumor microenvironment to overcome the immune-suppressive state; (3) Rewiring of tumor signaling: Liposomes can be used for the delivery of specific drugs to specific cell types to correct or modulate pathways to facilitate better anti-tumor immune responses; (4) Combinational therapy: Liposomes are ideal vehicles for the simultaneous delivery of drugs to be combined with other therapies, including chemotherapy, radiotherapy, and phototherapy. In this review, different liposomal systems specifically developed for immunomodulation in cancer are summarized and discussed.
What are liposomes used for?
Liposomes are lipid-based nanoparticles with high potential to improve cancer immunotherapies, since they can incorporate and/or associate a high variety of cancer drug molecules (e.g., peptides, proteins, antibodies, low-molecular weight chemotherapeutics) [30,31]. Liposomes are very versatile because they can be used for different kinds of immunotherapeutic cancer treatments (e.g., vaccination and checkpoint blockade), as Figure 2showed [32]. They are popular platforms for the controlled release of antigens, immunomodulators, and low-molecular-weight anti-cancer drugs [33]. The usage of liposomal-based drug delivery systems based in immunotherapy can be grouped into five different categories (Figure 3): (1) Vaccination: harnessing liposomes for the coordinated delivery of antigens and other stimulatory molecules to APCs or T cells, which employs the power of modern nanotechnology and yields improved outcomes as compared to conventional tumor antigen vaccination; (2) Tumor normalization: overcoming tumor-driven immunosuppressive signals (e.g., checkpoint blockade) in the TME by liposomes to improve selectivity and decrease systemic toxicity, which provides preliminary evidence of efficacy; (3) Tumor modulation: correcting or modulating an existing or known pathway during the development of the anti-tumor response; (4) Tumor targeting: targeting overexpressed surface molecules on cancer cells (may also be self-antigens) via B cell/antibody route or cancer-specific peptides presented on MHC-I on the cancer cells via Ag-specific T-cells, especially cytotoxic T-cells; and (5) Combinational therapy: exploring the combinational strategies between immunotherapy and others (e.g., chemotherapy, radiotherapy and phototherapy et al.), which provides opportunities for liposomes to co-load molecules with different properties.
What is the role of T cells in tumors?
Once activated, effector T cells must migrate to the tumor site and infiltrate the TME to perform their killing job . Here, negative regulatory signals that dampen T cell activation or induce anergy and exhaustion must be avoided as much as possible [8]. Typically, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) expressed on activated T cells are major suppressive costimulatory molecules, and therapeutic disruption with antagonistic antibodies has shown strong therapeutic potential [9,10]. Inside the abnormal TME, tumor populations, stromal cells, and multitudes of innate and adaptive immune cells together build up a complicated network to help tumor escape immune attacks through a variety of mechanisms [11,12,13,14]. Hence, an interesting strategy is to augment the anti-tumor immune response to overcome diverse immunosuppressive signals, which may be driven by both suppressive mediators and regulatory cell populations [15,16]. In this review, we have summarized the therapeutic strategies of immunomodulation in recent years and discuss the different mechanisms used to intervene with tumor immunity through the application of liposome technology.
How do liposomes target DCs?
(A) Liposomes can target DCs directly by receptor-mediated internalization. The induction of immune responses mediated by liposomes can increase the efficacy of cytotoxic T lymphocytes (CTLs) due to an enhanced uptake of antigens and adjuvants by DCs resulting in a higher upregulation of costimulatory receptors and the maturation of DCs. (B) Liposomes can activate cytotoxic CTLs and intensify the effector phase of immune responses. Direct T cell triggering can be achieved by liposomes that mimic natural APCs to provide persistent and strong activation as well as positive costimulation signals to T cells.
What is the best way to deliver RNA?
Fusogenic liposomes are regarded as ideal candidates for RNA delivery vehicles because delivery via fusogenic liposomes is one of the early proposed solutions to the problem of endocytic sequestration and the subsequent lysosomal degradation of RNA [93]. Synthetic molecules with fusogenic or membrane disruptive activity are normally used for the construction of liposomes to achieve membrane fusion [94]. After cellular internalization, fusogenic liposomes introduce the RNA into cytosol to achieve effective cellular immunity [95]. Stremersch et al. developed anionic fusogenic liposomes (equipped with cholesteryl hemisuccinate) and assed their siRNA delivery potential in B16F10 cancer cells and in the monocyte/DC (JAWSII) cell line [96]. These fusogenic liposomes successfully delivered cargo siRNA and resulted in a significant downregulation of the target gene expression. Normally, the endosomal/lysosomal escape of RNA is a major barrier for subsequent gene transcription in the cytoplasm. Recently, a new generation of fusogenic liposomes, which immediately fuse with the cellular plasma membrane upon contact, was developed and demonstrated in Chinese hamster ovary cells (CHO-K1) and human epidermal keratinocytes (nHEKs) [97]. It might also be interesting to extend this strategy for the cytoplasmic delivery of antigen coding RNA in DCs.
Why are liposomes important for immunotherapy?
Hence, the efficient and targeted delivery of these stimulatory molecules to the cells of interest is one of the important keys for successful cancer immunotherapy. Compared to injecting “free” drugs directly, liposomes can prevent cargos from degrading in the surrounding biological environment, improve their biodistribution, and promote their delivery to target cells. There are two well-known targets to improve immunotherapy through liposomes (Figure 4).
What is the structure of a liposome?
General scheme of liposomes. Liposomes are spherical vesicles with a hydrophilic core formed by a phospholipid and cholesterol bilayer. They can also be modified with polyethylene glycol (PEG) coating for long circulation and various molecules (peptides, antibodies, et al.) for targeting.
How to kill tumor cells?
Make an antibody to TCA protein and insert it into the liposome membrane. Fill interior of liposome with chemical toxic to cells. These liposomes should attach to tumor cells and be internalized after which toxic chemicals should kill tumor cells
What is the transition temperature of the first membrane?
You determine the transition temperatures for two membranes. The first has a transition temperature of 28°C, the second a transition temperature of 15°C. What can you conclude about the compositions of the two membranes?
What happens when you add more substrate to an enzyme reaction?
To the reaction mixture you add a chemical X which inhibits the reaction. If you add more substrate, the reaction rate approaches the Vmax of the uninhibited reaction. Furthermore, the structure of X is similar to the natural substrate. What kind of inhibitor is X?
What are the two molecules that pack together to form highly ordered microdomains that float within the more fluid and disorder?
cholesterol and sphingolipids tend to pack together to form highly ordered microdomains that float within the more fluid and disordered environment. Provide a favorable environment for cell-surface receptors and GPI- anchored proteins
What is chymotrypsin in the intestine?
chymotrypsin is a serine protease which hydrolyses peptide bond of protein in small intestine. Briefly explain the steps, including the reactivity of the three residues involve.
Does ATP slow down the glycolytic pathway?
The glycolytic pathway will probably slow down. ATP will act like a noncompetitive inhibitor and will inhibit one of the early glycolytic pathway