Photochemical Internalization for Intracellular Drug Delivery. From Basic Mechanisms to Clinical Research

Jerjes, Waseem; Theodossiou, Theodossis A.; Hirschberg, Henry; Høgset, Anders; Weyergang, Anette; Selbo, Pål Kristian; Hamdoon, Zaid; Hopper, Colin; Berg, Kristian

doi:10.3390/jcm9020528

Cited by 64 publications

(49 citation statements)

References 241 publications

(321 reference statements)

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“…Finally, the application of porphyrinic compounds in drug delivery should be mentioned in connection with the design of smart, stimuli-responsive platforms for controlled drug release. This includes for example photochemical internalization (PCI) [ 43 , 44 ] or porphyrin-based metal–organic frameworks (MOFs) [ 45 ]. Nanoplatforms have become an inevitable part in the application of porphyrinic drugs for solubilization, enhancing their efficiency and in vivo stability, and for passive and active tumor targeting [ 46 , 47 , 48 , 49 ].…”

Section: Introductionmentioning

confidence: 99%

Probing the Interactions of Porphyrins with Macromolecules Using NMR Spectroscopy Techniques

2021

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Porphyrinic compounds are widespread in nature and play key roles in biological processes such as oxygen transport in blood, enzymatic redox reactions or photosynthesis. In addition, both naturally derived as well as synthetic porphyrinic compounds are extensively explored for biomedical and technical applications such as photodynamic therapy (PDT) or photovoltaic systems, respectively. Their unique electronic structures and photophysical properties make this class of compounds so interesting for the multiple functions encountered. It is therefore not surprising that optical methods are typically the prevalent analytical tool applied in characterization and processes involving porphyrinic compounds. However, a wealth of complementary information can be obtained from NMR spectroscopic techniques. Based on the advantage of providing structural and dynamic information with atomic resolution simultaneously, NMR spectroscopy is a powerful method for studying molecular interactions between porphyrinic compounds and macromolecules. Such interactions are of special interest in medical applications of porphyrinic photosensitizers that are mostly combined with macromolecular carrier systems. The macromolecular surrounding typically stabilizes the encapsulated drug and may also modify its physical properties. Moreover, the interaction with macromolecular physiological components needs to be explored to understand and control mechanisms of action and therapeutic efficacy. This review focuses on such non-covalent interactions of porphyrinic drugs with synthetic polymers as well as with biomolecules such as phospholipids or proteins. A brief introduction into various NMR spectroscopic techniques is given including chemical shift perturbation methods, NOE enhancement spectroscopy, relaxation time measurements and diffusion-ordered spectroscopy. How these NMR tools are used to address porphyrin–macromolecule interactions with respect to their function in biomedical applications is the central point of the current review.

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Section: Introductionmentioning

confidence: 99%

Probing the Interactions of Porphyrins with Macromolecules Using NMR Spectroscopy Techniques

2021

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“…This approach features endocytic escape, as pioneered by Berg and colleagues [398], utilizing low/optimal doses of PSs and light, that are only sufficient for the selective rupturing of endocytic vesicles of the targeted cells, resulting in the cytosolic release of therapeutic contents. The strategy is being applied for many applications including gene delivery and clinical treatment of cancers where enhancement in chemotherapeutic drug delivery is needed [399].…”

Section: Targeted Delivery Of Nanomedicines For Photodynamic Therapymentioning

confidence: 99%

Photodynamic therapy, priming and optical imaging: Potential co-conspirators in treatment design and optimization — a Thomas Dougherty Award for Excellence in PDT paper

Silva

Saad

Thomsen

et al. 2020

J. Porphyrins Phthalocyanines

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Photodynamic therapy is a photochemistry-based approach, approved for the treatment of several malignant and non-malignant pathologies. It relies on the use of a non-toxic, light activatable chemical, photosensitizer, which preferentially accumulates in tissues/cells and, upon irradiation with the appropriate wavelength of light, confers cytotoxicity by generation of reactive molecular species. The preferential accumulation however is not universal and, depending on the anatomical site, the ratio of tumor to normal tissue may be reversed in favor of normal tissue. Under such circumstances, control of the volume of light illumination provides a second handle of selectivity. Singlet oxygen is the putative favorite reactive molecular species although other entities such as nitric oxide have been credibly implicated. Typically, most photosensitizers in current clinical use have a finite quantum yield of fluorescence which is exploited for surgery guidance and can also be incorporated for monitoring and treatment design. In addition, the photodynamic process alters the cellular, stromal, and/or vascular microenvironment transiently in a process termed photodynamic priming, making it more receptive to subsequent additional therapies including chemo- and immunotherapy. Thus, photodynamic priming may be considered as an enabling technology for the more commonly used frontline treatments. Recently, there has been an increase in the exploitation of the theranostic potential of photodynamic therapy in different preclinical and clinical settings with the use of new photosensitizer formulations and combinatorial therapeutic options. The emergence of nanomedicine has further added to the repertoire of photodynamic therapy’s potential and the convergence and co-evolution of these two exciting tools is expected to push the barriers of smart therapies, where such optical approaches might have a special niche. This review provides a perspective on current status of photodynamic therapy in anti-cancer and anti-microbial therapies and it suggests how evolving technologies combined with photochemically-initiated molecular processes may be exploited to become co-conspirators in optimization of treatment outcomes. We also project, at least for the short term, the direction that this modality may be taking in the near future.

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“…Previously developed light-controlled gene delivery technologies involve optical transfection (6,7), photochemical internalization (8), and light-controlled viral transduction (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). Although optical transfection based on laser-induced cell membrane perforation allows high spatial control, it is accompanied by high cell toxicity and restriction to small irradiation areas (4,7).…”

Section: Introductionmentioning

confidence: 99%

Spatiotemporally confined red light-controlled gene delivery at single-cell resolution using adeno-associated viral vectors

et al. 2021

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Methodologies for the controlled delivery of genetic information into target cells are of utmost importance for genetic engineering in both fundamental and applied research. However, available methods for efficient gene transfer into user-selected or even single cells suffer from low throughput, the need for complicated equipment, high invasiveness, or side effects by off-target viral uptake. Here, we engineer an adeno-associated viral (AAV) vector system that transfers genetic information into native target cells upon illumination with cell-compatible red light. This OptoAAV system allows adjustable and spatially resolved gene transfer down to single-cell resolution and is compatible with different cell lines and primary cells. Moreover, the sequential application of multiple OptoAAVs enables spatially resolved transduction with different transgenes. The approach presented is likely extendable to other classes of viral vectors and is expected to foster advances in basic and applied genetic research.

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Photochemical Internalization for Intracellular Drug Delivery. From Basic Mechanisms to Clinical Research

Cited by 64 publications

References 241 publications

Probing the Interactions of Porphyrins with Macromolecules Using NMR Spectroscopy Techniques

Probing the Interactions of Porphyrins with Macromolecules Using NMR Spectroscopy Techniques

Photodynamic therapy, priming and optical imaging: Potential co-conspirators in treatment design and optimization — a Thomas Dougherty Award for Excellence in PDT paper

Spatiotemporally confined red light-controlled gene delivery at single-cell resolution using adeno-associated viral vectors

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