Photopharmacology

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History

Photopharmacology is an emerging multidisciplinary field that combines photochemistry and pharmacology. [1] Built upon the ability of light to change the pharmacokinetics and pharmacodynamics of bioactive molecules, it aims at regulating the activity of drugs in vivo by using light. [2] The light-based modulation is achieved by incorporating molecular photoswitches such as azobenzene and diarylethenes or photocages such as o-nitrobenzyl, coumarin, and BODIPY compounds into the pharmacophore. [3] This selective activation of the biomolecules helps prevent or minimize off-target activity and systemic side effects. Moreover, light being the regulatory element offers additional advantages such as the ability to be delivered with high spatiotemporal precision, low to negligible toxicity, and the ability to be controlled both qualitatively and quantitatively by tuning its wavelength and intensity. [4]

Contents

Though photopharmacology is a relatively new field, the concept of using light in therapeutic applications came into practice a few decades ago. Photodynamic therapy (PTD) is a well-established clinically practiced protocol in which photosensitizers are used to produce singlet oxygen for destroying diseased or damaged cells or tissues. [2] Optogenetics is another method that relies on light for dynamically controlling biological functions especially brain and neural. [4] Though this approach has proven useful as a research tool, its clinical implementation is limited by the requirement for genetic manipulation. Mainly, these two techniques laid the foundation for photopharmacology. Today, it is a rapidly evolving field with diverse applications in both basic research and clinical medicine which has the potential to overcome some of the challenges limiting the range of applications of the other light-guided therapies. Photopharma.jpg Figure 1. Schematic representation of the mechanism of (a) photopharmacology (b) photodynamic therapy, and (c) optogenetics

The discovery of natural photoreceptors such as rhodopsins in the eye inspired the biomedical and pharmacology research community to engineer light-sensitive proteins for therapeutic applications. [2] The development of synthetic photoswitchable molecules is the most significant milestone in the history of light-delivery systems. Scientists are continuing with their efforts to explore new photoswitches and delivery strategies with enhanced performance to target different biological molecules such as ion channels, nucleic acid, and enzyme receptors. Photopharmacology research progressed from in vitro to in vivo studies in a significantly short period of time yielding promising results in both forms. Clinical trials are underway to assess the safety and efficacy of these photopharmacological therapies further and validate their potential as an innovative drug delivery approach.

Mechanism of Action

Molecular photoswitches are utilized in the field of photopharmacology, where the energetics of a molecule can be reversibly controlled with light to achieve spatial and temporal resolution of a particular effect. Photoswitches may function by undergoing photoisomerization through which light is used to conformationally adapt a molecule to a biological site, or through an environmental effect where an external factor such as a solvent effect or hydrogen bonding can selectively allow or quench an emissive state within a molecule. To visualize photophysical processes, a useful depiction is the Jablonski diagram. This is a diagram which depicts electronic and vibrational energy levels within a molecule as vertical levels and shows the possible relaxation pathways from excited states. Typically, the ground state is referred to as S0, and is drawn at the bottom of the figure with nearby vibrational excitations just above it. An absorption will promote an electron into the S1 state at any vibrational energy level, or into a higher order excited state if the absorbed energy has enough magnitude. The excited state can then undergo internal conversion which is the electronic relaxation to a lower state with the same vibrational energetics or vibrational relaxation within a state. This may be followed by an intersystem crossing wherein the electron undergoes a spin flip, or a radiative or nonradiative decay back to the ground state. [5]

Figure 2. A representative Jablonski diagram. RepJablonski.png
Figure 2. A representative Jablonski diagram.

One example of an organic compound that undergoes photoisomerization is azobenzene. The structure is two phenyl rings joined with a N=N double bond and is the simplest aryl azo compound. Azobenzene and its derivatives have two accessible absorbance bands: the S1 state from a n-π* transition which can be excited into using blue light, and the S2 state from a π-π* transition that can be excited into using ultraviolet light. [6] Azobenzene and its derivatives have two isomers, trans and cis. The trans isomer, having the phenyl rings on opposite sides of the azo double bond, is the thermally preferred isomer as there is less stereoelectronic distortion and more delocalization present. However, excitation of the trans isomer to the S2 state facilitates a shift to the cis isomer. The S1 absorption is associated with a conversion back to the trans isomer. In this way, azobenzene and its derivatives can act as reversible stores of energy by maintaining a strained configuration in the cis isomer. Modifications of the substituents on azobenzene allow the energetics of these absorptions to be tuned, and if they are engineered such that the two absorption bands overlap a single wavelength of light can be used to flip between them. There are a number of similar photoswitches which isomerize between E and Z configurations across an azo group (for instance, azobenzene and azopyrazole) or an ethylene bridge (for instance, stilbene and hemithioindigo). [7]

Figure 3. (Top.) Renditions of the L and D enantiomers of [Ru(phen)2dppz] , where phen=1,10-phenanthroline and dppz=dipyrido[3,2-a:2,3-c]phenazine. (Bottom.) Jablonski diagram representing the aqueous quenching of [Ru(phen)2dppz] emission, depicting bright states and dark states. Ru and jablonski.png
Figure 3. (Top.) Renditions of the Λ and Δ enantiomers of [Ru(phen)2dppz] , where phen=1,10-phenanthroline and dppz=dipyrido[3,2-a:2,3-c]phenazine. (Bottom.) Jablonski diagram representing the aqueous quenching of [Ru(phen)2dppz] emission, depicting bright states and dark states.

Alternatively, photoswitches may themselves be emissive and exhibit environmental control over their properties. One such example is a class of ruthenium polypyridyl coordination complexes. Typically they contain two bidentate bipyridine or phenanthroline ligands and an extended phenanthroline-phenazine bidentate ligand such as dipyrido[3,2-a:2,3-c]phenazine (dppz). [8] These complexes have an accessible metal to ligand charge transfer excited state (1MLCT) which undergoes rapid intersystem crossing to a 3MLCT state due to the strong spin-orbit coupling of the ruthenium center. These excited states are localized on the extended ligand phenazine nitrogens, and emission occurs from the 3MLCT state. Hydrogen bonding interactions such as the presence of water around these nitrogen atoms stabilizes the 3MLCT state, quenching the emission process. Thus, by controlling whether an aqueous or otherwise protic polar solvent is present, emissive behaviors can be “turned on/off”, and alternation between “bright states” and “dark states” is facilitated. This light switch behavior makes these and similar complexes of recent interest in photopharmacological applications such as photodynamic therapy.

Molecules

As previously mentioned, photopharmacology relies on the use of molecular photoswitches being incorporated into the structure of biologically active molecules which allows their potency to be controlled optically. [7] They are introduced into the structure of bioactive compounds via insertion, extension, or bioisosteric replacement. [7] These incorporations can be supported by structural considerations of the molecule or SAR (structure-activity relationship) analysis to determine the optimal position. [7] Some examples of photoswitchable molecules commonly used in photopharmacology are azobenzenes, diarylethenes, and photocages. [9]

Azobenzenes

Azobenzenes are a class of photoswitchable molecules and are used in photopharmalogical applications for their reversible photoisomerization, as described in the previous section. An example of a photoswitchable molecule that uses azobenzene is phototrexate. Phototrexate is an inhibitor of human dihydrofolate reductase and is an analogue of methotrexate, a chemotherapy agent. [10] When in its photoactive cis form, phototrexate has been shown to be a potent antifolate and is relatively inactive when in the trans form. [10] The azologization, or incorporation of azobenzene, of methotrexate allows for control of cytotoxic activity and is considered a step forward in developing targeted anticancer drugs with localized efficacy. [10]

Diarylethenes

Diarylethene photoswitches have reversible cyclization and cycloreversion reactions that are photoinduced. [11] They are a class of compounds that have aromatic functional groups bonded to each end of a carbon-carbon double bond. An example of this class of molecule that is used in photopharmacology is stilbene. Under the influence of light, stilbene switches between its two isomers (E and Z).

Stilbene isomerization.svg

Figure 4. Figure showing stilbene isomerizations under light from E to Z

Diarylethenes have been shown to have some advantages over the more researched azobenzenes switches, such as thermal irreversibility, high photoswitching efficiency, favorable cellular stability, and low toxicity. [11] Diarylethenes have been shown to have promise in fields other than photopharmacology as well. These fields include optical data storage, optoelectronic devices, supramolecular self-assembly and anti-counterfeiting. [11]

Photocages

A class of substances known as photocages contain “photosensitive groups, also known as ‘photoremovable protecting groups’, from which target substances are released upon exposure to specific wavelengths of light”. [12] The photosensitive groups physically and chemically protect the target from being released until the molecule undergoes photoreaction. [12] Due to these interactions with light, they are commonly used molecules in photopharmacology. More recently, they have played an important role in photoactivated chemotherapy (PACT). In PACT, photocages utilize a photoremovable protecting group that protects cytotoxic drugs until the bond is cleaved via light interaction and the cytotoxic drug is released. [13] Some well-known photocages include “o-nitrobenzyl derivatives, coumarin derivatives, BODIPY, xanthene derivatives, quinone and diarylenes derivatives”. [12] However, there are limitations with using photocages in clinical applications as there are not many PPGs that can be used in vivo. This is due to PPG-payload conjugates needing to have acceptable solubility and biological inertness for biocompatibility and the need for efficient uncaging above 600 nm. [13] Photocage Example Process.jpg

Figure 5. Example of a photocage release system activated by NIR [14]

Application

Photopharmacology, the use of light to control the activity of drugs, has emerged as a promising approach to drug delivery and therapy. By harnessing the power of light, researchers can achieve precise control over drug release and activation, offering new possibilities for targeted and personalized treatments. In this subsection, we explore the application of photopharmacology in drug delivery, focusing on recent advancements and potential clinical applications. In this study [15] researchers designed HDAC inhibitors which can be activated or deactivated with light, providing precise therapeutic control. This approach could reduce the side effects of traditional chemotherapy by targeting inhibitors to specific body areas, potentially leading to more effective and personalized cancer treatments.

Figure 6. Comparison of the principles behind classic chemotherapy and photo pharmacological chemotherapy Photopharamacology.png
Figure 6. Comparison of the principles behind classic chemotherapy and photo pharmacological chemotherapy

In this study, [16] the researchers developed a strategy to attach a photoswitchable group to a common antibiotic; ciprofloxacin. By attaching the photoswitchable group, researchers can control the activity of ciprofloxacin with light. This approach could potentially lead to new ways of treating bacterial infections, with the ability to switch the antibiotic's activity on and off as needed. In this paper [17] an in vitro protocol to test different light wavelengths on human cancer cell lines is developed, finding that blue light most effectively inhibited cell growth. This suggests that photopharmacology could offer new cancer treatment options by targeting specific light wavelengths to modulate drug activity in tumor cells. Another application of photopharmacology [18] is developing a luminescent photoCORM grafted on carboxymethyl chitosan, which, when exposed to light, releases carbon monoxide (CO) to induce apoptotic death in colorectal cancer cells, demonstrating precise control over CO release for targeted cancer therapy. Researchers developed a toolbox of photoswitchable antagonists that can interact with GPCRs, a class of proteins involved in various cellular processes. [19] By using light to switch the activity of these antagonists, researchers can control the interaction between the antagonists and GPCRs in real time. This approach allows for precise modulation of GPCR activity, which could lead to new insights into cellular signaling pathways and potential therapeutic applications. In another application [20] by using light to control the assembly of nanopores, researchers can potentially regulate the flow of ions or molecules through these nanopores. This approach could have applications in various fields, including sensing, drug delivery, and nanotechnology. In this paper [21] they’ve used Photopharmacology to control drug activity; multifunctional fibers in the study deliver light and drugs to specific body areas. Implanted fibers activate light-responsive drugs, altering their structure, and offering precise drug delivery for conditions needing exact timing or dosage. In another study, [22] ligands were designed to switch their binding mode to G-quadruplex DNA upon exposure to visible light. This method could potentially modulate the activity of G-quadruplex DNA, crucial in gene expression and telomere maintenance, offering new therapeutic avenues, particularly in cancer treatment. The study underscores photopharmacology's promise in targeting specific DNA structures, suggesting G-quadruplex DNA as a viable target for future photopharmacological interventions. This study [23] developed photoactivatable antibody-photoCORM conjugates targeting human ovarian cancer cells, releasing CO upon light exposure to diminish cell viability. This approach offers precise cancer cell targeting while minimizing harm to healthy tissue, showcasing the potential of photopharmacology in cancer therapy. In this paper, [24] a photoactivatable compound that binds to and modulates the activity of the CRY1 protein, regulating the mammalian circadian clock has been developed. By using light to control the compound's activity, researchers can potentially treat circadian rhythm disorders and related health conditions by modulating the function of CRY1. Photopharmacology involves using light to control the activity of drugs. In another application [25] researchers use photopharmacology to control drug release and focus on a drug interacting with tubulin, visualizing its release in real time with time-resolved serial crystallography. This technique offers insights into drug-tubulin interactions and demonstrates the potential for designing drugs with precise actions.


Future Directions

The future of photopharmacology holds immense promise. It has the potential to revolutionize conventional drug therapy offering new avenues for precision medicine, treating neurological disorders, and in the field of oncology and ophthalmology. [1] Additionally, it holds promise for the field of regenerative medicine where photoswitches can be used to modulate the activity of signaling pathways for targeted tissue repair and regeneration. [3]

Photopharmacology will continue to grow and expand with the new discoveries and advances happening in other related fields such as synthetic chemistry, biology, nanotechnology, pharmacology, and bioengineering. While the potential of photopharmacology is vast, there are some challenges that need to be addressed to make it a clinical reality.  One such challenge is the development of stable and biocompatible photoswitches that are selective for their target receptors without cross-activity. [2] It is particularly important that these photoswitchables have their absorbance bands fall within the wavelength range of 650 nm to 900 nm. [2] Hence, optimum molecular designing of photoswitches is required to achieve the characteristics mentioned above and desired level of performance. At present, photopharmacology uses a rational drug design approach based on studying the structure-activity relationship, however, a phenotypic screening for photoswitchable drugs could also be beneficial.

In order to achieve good spatial-temporal control over drug activity there should be a significant difference between the activity of isomers. However, understanding the structural changes during the biological effects induced by photoswitching is limited. This scarcity of knowledge is also a challenge for the growth of this field as it hampers the optimization of the activity and potency of the isomers to obtain the expected outcomes during applications. [3]

Another hurdle, the biggest challenge in photopharmacology is finding appropriate and effective ways to deliver light to deep tissues in the body and tissues avoiding issues such as scattering and absorption. Various strategies have been attempted in this regard, one being the development of photoswitchable ligands that respond to deep-tissue penetrating wavelengths like red or infrared light. Moreover, some recent preclinical studies have spurred the development of wireless, compact or injectable, and remotely controllable devices capable of delivering light to neural tissues with minimal damage. [26] There are novel optofluidic systems that can simultaneously regulate both drug delivery and light activity at specific sites.  Although, external delivery of light is the most preferred method, the use of internal exogenous light sources such as luminescent compounds where light would be delivered directly at the site of action. This could avoid the issues related to light penetration and also enhance the degree of selectivity. In addition, this creates the opportunity to use photopharmacology as a theranostic approach that combines targeted drug delivery and molecular imaging. [2]

Related Research Articles

<span class="mw-page-title-main">Azobenzene</span> Two phenyl rings linked by a N═N double bond

Azobenzene is a photoswitchable chemical compound composed of two phenyl rings linked by a N=N double bond. It is the simplest example of an aryl azo compound. The term 'azobenzene' or simply 'azo' is often used to refer to a wide class of similar compounds. These azo compounds are considered as derivatives of diazene (diimide), and are sometimes referred to as 'diazenes'. The diazenes absorb light strongly and are common dyes. Different classes of azo dyes exist, most notably the ones substituted with heteroaryl rings.

In chemistry, photoisomerization is a form of isomerization induced by photoexcitation. Both reversible and irreversible photoisomerizations are known for photoswitchable compounds. The term "photoisomerization" usually, however, refers to a reversible process.

<span class="mw-page-title-main">Receptor-mediated endocytosis</span> Process by which cells absorb materials

Receptor-mediated endocytosis (RME), also called clathrin-mediated endocytosis, is a process by which cells absorb metabolites, hormones, proteins – and in some cases viruses – by the inward budding of the plasma membrane (invagination). This process forms vesicles containing the absorbed substances and is strictly mediated by receptors on the surface of the cell. Only the receptor-specific substances can enter the cell through this process.

<span class="mw-page-title-main">Molecular machine</span> Molecular-scale artificial or biological device

Molecular machines are a class of molecules typically described as an assembly of a discrete number of molecular components intended to produce mechanical movements in response to specific stimuli, mimicking macromolecular devices such as switches and motors. Naturally occurring or biological molecular machines are responsible for vital living processes such as DNA replication and ATP synthesis. Kinesins and ribosomes are examples of molecular machines, and they often take the form of multi-protein complexes. For the last several decades, scientists have attempted, with varying degrees of success, to miniaturize machines found in the macroscopic world. The first example of an artificial molecular machine (AMM) was reported in 1994, featuring a rotaxane with a ring and two different possible binding sites. In 2016 the Nobel Prize in Chemistry was awarded to Jean-Pierre Sauvage, Sir J. Fraser Stoddart, and Bernard L. Feringa for the design and synthesis of molecular machines.

<span class="mw-page-title-main">Photochromism</span> Reversible chemical transformation by absorption of electromagnetic radiation

Photochromism is the reversible change of color upon exposure to light. It is a transformation of a chemical species (photoswitch) between two forms by the absorption of electromagnetic radiation (photoisomerization), where the two forms have different absorption spectra.

<span class="mw-page-title-main">Photosensitizer</span> Type of molecule reacting to light

Photosensitizers are light absorbers that alter the course of a photochemical reaction. They usually are catalysts. They can function by many mechanisms, sometimes they donate an electron to the substrate, sometimes they abstract a hydrogen atom from the substrate. At the end of this process, the photosensitizer returns to its ground state, where it remains chemically intact, poised to absorb more light. One branch of chemistry which frequently utilizes photosensitizers is polymer chemistry, using photosensitizers in reactions such as photopolymerization, photocrosslinking, and photodegradation. Photosensitizers are also used to generate prolonged excited electronic states in organic molecules with uses in photocatalysis, photon upconversion and photodynamic therapy. Generally, photosensitizers absorb electromagnetic radiation consisting of infrared radiation, visible light radiation, and ultraviolet radiation and transfer absorbed energy into neighboring molecules. This absorption of light is made possible by photosensitizers' large de-localized π-systems, which lowers the energy of HOMO and LUMO orbitals to promote photoexcitation. While many photosensitizers are organic or organometallic compounds, there are also examples of using semiconductor quantum dots as photosensitizers.

Solar chemical refers to a number of possible processes that harness solar energy by absorbing sunlight in a chemical reaction. The idea is conceptually similar to photosynthesis in plants, which converts solar energy into the chemical bonds of glucose molecules, but without using living organisms, which is why it is also called artificial photosynthesis.

A photoswitch is a type of molecule that can change its structural geometry and chemical properties upon irradiation with electromagnetic radiation. Although often used interchangeably with the term molecular machine, a switch does not perform work upon a change in its shape whereas a machine does. However, photochromic compounds are the necessary building blocks for light driven molecular motors and machines. Upon irradiation with light, photoisomerization about double bonds in the molecule can lead to changes in the cis- or trans- configuration. These photochromic molecules are being considered for a range of applications.

A molecular switch is a molecule that can be reversibly shifted between two or more stable states. The molecules may be shifted between the states in response to environmental stimuli, such as changes in pH, light, temperature, an electric current, microenvironment, or in the presence of ions and other ligands. In some cases, a combination of stimuli is required. The oldest forms of synthetic molecular switches are pH indicators, which display distinct colors as a function of pH. Currently synthetic molecular switches are of interest in the field of nanotechnology for application in molecular computers or responsive drug delivery systems. Molecular switches are also important in biology because many biological functions are based on it, for instance allosteric regulation and vision. They are also one of the simplest examples of molecular machines.

<span class="mw-page-title-main">Meir Wilchek</span> Israeli biochemist (born 1935)

Meir Wilchek is an Israeli biochemist. He is a professor at the Weizmann Institute of Science.

<span class="mw-page-title-main">Stefan Hecht</span> German chemist (born 1974)

Stefan Hecht is a German chemist.

<span class="mw-page-title-main">Photoactivated peptide</span>

Photoactivated peptides are modified natural or synthetic peptides the functions of which can be activated with light. This can be done either irreversibly or in a reversible way. Caged peptides which contain photocleavable protecting groups belong to irreversibly activated peptides. Reversible activation/deactivation of peptide function are achieved by incorporation photo-controllable fragments in the side chains or in the backbone of peptide templates to get the photo-controlled peptides, which can reversibly change their structure upon irradiation with light of different wavelength. As the consequence, the properties, function and biological activity of the modified peptides can be controlled by light. Since light can be directed to specific areas, such peptides can be activated only at targeted sites. Azobenzenes, and diarylethenes can be used as the photoswitches. For therapeutic use, photoswitches with longer wavelengths or the use of two-photon excitation are required, coupled with improved methods for peptide delivery to live cells.

<span class="mw-page-title-main">Ben Feringa</span> Dutch Nobel laureate in chemistry

Bernard Lucas Feringa is a Dutch synthetic organic chemist, specializing in molecular nanotechnology and homogeneous catalysis. He is the Jacobus van 't Hoff Distinguished Professor of Molecular Sciences, at the Stratingh Institute for Chemistry, University of Groningen, Netherlands, and an Academy Professor of the Royal Netherlands Academy of Arts and Sciences. He was awarded the 2016 Nobel Prize in Chemistry, together with Sir J. Fraser Stoddart and Jean-Pierre Sauvage, "for the design and synthesis of molecular machines".

<span class="mw-page-title-main">Targeted covalent inhibitors</span>

Targeted covalent inhibitors (TCIs) or Targeted covalent drugs are rationally designed inhibitors that bind and then bond to their target proteins. These inhibitors possess a bond-forming functional group of low chemical reactivity that, following binding to the target protein, is positioned to react rapidly with a proximate nucleophilic residue at the target site to form a bond.

Photostatins are inhibitors that can be switched on and off in vivo by visible light, to optically control microtubule dynamics. Photostatins are a form of photopharmacology.

Igor Volodymyrovych Komarov is a Ukrainian synthetic organic chemist, specializing in medicinal chemistry and nanotechnology. He is the director of the Institute of High Technologies of Taras Shevchenko National University of Kyiv. He is also a scientific advisor of Enamine Ltd (Ukraine) and Lumobiotics GmbH (Germany).

<span class="mw-page-title-main">Phototrexate</span> Photopharmacological agent

Phototrexate is a photochromic antifolate drug developed at the Institute for Bioengineering of Catalonia. In particular, it is a photopharmacological agent that behaves as light-regulated inhibitor of the dihydrofolate reductase (DHFR) enzyme. Phototrexate is a photoisomerizable structural analogue of the chemotherapy agent methotrexate. It is also an example of "azologization". Pharmacological effects of phototrexate can be switched on and off by UVA and visible light, respectively. Phototrexate is almost inactive in its trans configuration while it behaves as a potent antifolate in its cis configuration. It can also spontaneously self-deactivate in the dark.

<span class="mw-page-title-main">Polymer-protein hybrid</span> Nanostructures of protein-polymer conjugates

Polymer-protein hybrids are a class of nanostructure composed of protein-polymer conjugates. The protein component generally gives the advantages of biocompatibility and biodegradability, as many proteins are produced naturally by the body and are therefore well tolerated and metabolized. Although proteins are used as targeted therapy drugs, the main limitations—the lack of stability and insufficient circulation times still remain. Therefore, protein-polymer conjugates have been investigated to further enhance pharmacologic behavior and stability. By adjusting the chemical structure of the protein-polymer conjugates, polymer-protein particles with unique structures and functions, such as stimulus responsiveness, enrichment in specific tissue types, and enzyme activity, can be synthesized. Polymer-protein particles have been the focus of much research recently because they possess potential uses including bioseparations, imaging, biosensing, gene and drug delivery.

Matthew John Fuchter is a British chemist who is a Professor of Chemistry at Imperial College London. His research focuses on the development and application of novel functional molecular systems to a broad range of areas; from materials to medicine. He has been awarded both the Harrison-Meldola Memorial Prize (2014) and the Corday–Morgan Prizes (2021) of the Royal Society of Chemistry. In 2020 he was a finalist for the Blavatnik Awards for Young Scientists.

<span class="mw-page-title-main">Ligand-targeted liposome</span> Ligand-targeted liposomes for use in medical applications

A ligand-targeted liposome (LTL) is a nanocarrier with specific ligands attached to its surface to enhance localization for targeted drug delivery. The targeting ability of LTLs enhances cellular localization and uptake of these liposomes for therapeutic or diagnostic purposes. LTLs have the potential to enhance drug delivery by decreasing peripheral systemic toxicity, increasing in vivo drug stability, enhancing cellular uptake, and increasing efficiency for chemotherapeutics and other applications. Liposomes are beneficial in therapeutic manufacturing because of low batch-to-batch variability, easy synthesis, favorable scalability, and strong biocompatibility. Ligand-targeting technology enhances liposomes by adding targeting properties for directed drug delivery.

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