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Updated: Sep 26, 2026
Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles
Published on: December 1, 2016
[Targeted intracellular site-specific drug delivery: photosensitizer targeting to melanoma cell nuclei]
A A Rozenkrants1, V G Lunin, O V Sergienko
1Institute of Gene Biology, Russian Academy of Sciences, Department of Biophysics, Lomonosov Moscow State University, Moscow, Russia.
Abstract:
A number of drugs are regarded as possessing local activity because their effects take place at an extremely short distance from their location site in the cell. The response of different cellular compartments to these effects is different. Such substances as photosensitizers (PSs), which are used in photodynamic cancer therapy, should be targeted to the cell compartments where their effect is the most pronounced. This study describes the construction and properties of the chimeric modular recombinant transporters (MRTs) expressed in Escherichia coli and used for PS targeting. These constructs include (1) the alpha-melanocyte-stimulating hormone as a ligand module, which is internalized by the target cells (mouse melanoma); (2) the optimized SV40 large T-antigen nuclear localization signal; (3) the hemoglobin-like protein from E. coli as a carrier module; (4) the endosomolytic module, the translocation domain of the diphtheria toxin. These MRTs were used for PS targeting to the mouse melanoma cell nuclei, the most PS-damaged intracellular compartment, which resulted in a PS photocytotoxic effect increase of several orders of magnitude. In our opinion, MRTs, which target locally active drugs into the desired cell compartment and thereby enhance the drug response, represent a new generation of the pharmacological agents.
Insights
Modular recombinant transporters (MRTs) effectively target photosensitizers (PSs) to mouse melanoma cell nuclei, significantly enhancing photodynamic cancer therapy efficacy. This novel drug delivery approach improves therapeutic outcomes by concentrating PSs in the most responsive cellular compartments.
Area of Science:
- Biotechnology
- Pharmacology
- Cancer Therapy
Background:
- Locally active drugs require precise cellular targeting for optimal efficacy.
- Photosensitizers (PSs) in photodynamic therapy (PDT) show varied responses based on cellular compartment localization.
- Targeting PSs to specific intracellular sites can enhance their photocytotoxic effect.
Purpose of the Study:
- To construct and characterize chimeric modular recombinant transporters (MRTs) for targeted drug delivery.
- To utilize MRTs for directing photosensitizers (PSs) to specific cellular compartments.
- To evaluate the impact of targeted PS delivery on photocytotoxic effect in mouse melanoma cells.
Main Methods:
- Construction of modular recombinant transporters (MRTs) in Escherichia coli.
- Incorporation of specific modules: alpha-melanocyte-stimulating hormone, SV40 large T-antigen NLS, E. coli hemoglobin-like protein, and diphtheria toxin translocation domain.
- Application of MRTs for targeting PSs to mouse melanoma cell nuclei.
- Assessment of photocytotoxic effect enhancement.
Main Results:
- Successfully constructed functional MRTs capable of cellular internalization and intracellular targeting.
- Achieved targeted delivery of PSs to the nuclei of mouse melanoma cells.
- Demonstrated a significant increase (several orders of magnitude) in PS photocytotoxic effect due to nuclear targeting.
Conclusions:
- Modular recombinant transporters (MRTs) represent a novel platform for targeted drug delivery.
- Targeting locally active drugs like PSs to specific cellular compartments enhances therapeutic efficacy.
- MRTs offer a new generation of pharmacological agents for improved cancer treatment outcomes.
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