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Single- versus Dual-Targeted Nanoparticles with Folic Acid and Biotin for Anticancer Drug Delivery

Jurczyk, Magdalena, Jelonek, Katarzyna, Musiał-Kulik, Monika, Beberok, Artur, Wrześniok, Dorota, Kasperczyk, Janusz·2021·Pharmaceutics
DOI 10.3390/pharmaceutics13030326PMC PMC8001342
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Abstract

Cancer is one of the major causes of death worldwide and its treatment remains very challenging. The effectiveness of cancer therapy significantly depends upon tumour-specific delivery of the drug. Nanoparticle drug delivery systems have been developed to avoid the side effects of the conventional chemotherapy. However, according to the most recent recommendations, future nanomedicine should be focused mainly on active targeting of nanocarriers based on ligand-receptor recognition, which may show better efficacy than passive targeting in human cancer therapy. Nevertheless, the efficacy of single-ligand nanomedicines is still limited due to the complexity of the tumour microenvironment. Thus, the NPs are improved toward an additional functionality, e.g., pH-sensitivity (advanced single-targeted NPs). Moreover, dual-targeted nanoparticles which contain two different types of targeting agents on the same drug delivery system are developed. The advanced single-targeted NPs and dual-targeted nanocarriers present superior properties related to cell selectivity, cellular uptake and cytotoxicity toward cancer cells than conventional drug, non-targeted systems and single-targeted systems without additional functionality. Folic acid and biotin are used as targeting ligands for cancer chemotherapy, since they are available, inexpensive, nontoxic, nonimmunogenic and easy to modify. These ligands are used in both, single- and dual-targeted systems although the latter are still a novel approach. This review presents the recent achievements in the development of single- or dual-targeted nanoparticles for anticancer drug delivery.

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Figure 1 Chemical structure of folic acid and biotin.
Figure 1 Chemical structure of folic acid and biotin.CC BY · PubMed Central
Figure 2 Scheme of different kinds of FA-targeted nanoparticles. After modification from (reproduced from Farran et al. [13]).
Figure 2 Scheme of different kinds of FA-targeted nanoparticles. After modification from (reproduced from Farran et al. [13]).CC BY · PubMed Central
Figure 3 Confocal images showing the subcellular distribution of PLA-Jeff-FA/PLA3000PEG2000 micelles with fluorescein after 24 h incubation with HeLa cells (A) and normal human connective tissue cells (B) (reproduced from Jelonek et al. [81]).
Figure 3 Confocal images showing the subcellular distribution of PLA-Jeff-FA/PLA3000PEG2000 micelles with fluorescein after 24 h incubation with HeLa cells (A) and normal human connective tissue cells (B) (reproduced from Jelonek et al. [81]).CC BY · PubMed Central
Figure 4 Schematic presentation of the two biotinylation strategies. With permission from [112].
Figure 4 Schematic presentation of the two biotinylation strategies. With permission from [112].CC BY · PubMed Central
Figure 5 A schematic presentation (A) and TEM image at a scale = 100 nm (B) of DOX-PLGA-lecithin-PEG-biotin nanoparticles (B). With permission from Dai et al. [120].
Figure 5 A schematic presentation (A) and TEM image at a scale = 100 nm (B) of DOX-PLGA-lecithin-PEG-biotin nanoparticles (B). With permission from Dai et al. [120].CC BY · PubMed Central
Figure 6 The structure of biotinylated multi-seed polymeric liposomes and mechanism of stimuli-responsive size/ligand adapting strategy with the two-step method of the biotin-avidin system. 1-targeting delivery of nanocarriers to the tumour; 2-off-targeting scavenging of nanocarriers in blood and normal tissues by avidin. With permission from Jin et al. [129].
Figure 6 The structure of biotinylated multi-seed polymeric liposomes and mechanism of stimuli-responsive size/ligand adapting strategy with the two-step method of the biotin-avidin system. 1-targeting delivery of nanocarriers to the tumour; 2-off-targeting scavenging of nanocarriers in blood and normal tissues by avidin. With permission from Jin et al. [129].CC BY · PubMed Central
Figure 7 Scheme of three types of dual-molecular targeting: (A) dual-targeting nanocarriers target one kind of cell; (B) dual-targeting nanocarriers target simultaneously various cells; (C) Dual-targeting nanocarriers target cells that overexpress one kind of receptor on the cell and another kind of receptor inside cells on nuclei or mitochondria. With permission from Zhu et al. [6].
Figure 7 Scheme of three types of dual-molecular targeting: (A) dual-targeting nanocarriers target one kind of cell; (B) dual-targeting nanocarriers target simultaneously various cells; (C) Dual-targeting nanocarriers target cells that overexpress one kind of receptor on the cell and another kind of receptor inside cells on nuclei or mitochondria. With permission from Zhu et al. [6].CC BY · PubMed Central
Figure 8 Scheme of the concept of cell uptake and drug release from Bio-oHA-Hyd-FA carriers. With permission from Tomeh et al. [200].
Figure 8 Scheme of the concept of cell uptake and drug release from Bio-oHA-Hyd-FA carriers. With permission from Tomeh et al. [200].CC BY · PubMed Central
Figure 9 Evolution of nanoparticulate delivery system of anticancer drugs toward improvement of efficiency and decrease of toxicity.
Figure 9 Evolution of nanoparticulate delivery system of anticancer drugs toward improvement of efficiency and decrease of toxicity.CC BY · PubMed Central

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Metadata

Authors
Jurczyk, M., Jelonek, K., Musiał-Kulik, M., Beberok, A., Wrześniok, D., & Kasperczyk, J.
Venue
Pharmaceutics
Publisher
MDPI AG
Published
2021-03-03
Volume
13
Issue
3
Pages
326
ISSN
1999-4923
DOI
10.3390/pharmaceutics13030326
PMC
PMC8001342
Cited by
133
References
4
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
Narodowe Centrum Nauki (2019/34/E/NZ7/00010)

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CoChat. (2026). Citation check: Single- versus Dual-Targeted Nanoparticles with Folic Acid and Biotin for Anticancer Drug Delivery. https://app.cochat.ai/papers/10.3390/pharmaceutics13030326
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Jurczyk, M., Jelonek, K., Musiał-Kulik, M., Beberok, A., Wrześniok, D., & Kasperczyk, J. (2021). Single- versus Dual-Targeted Nanoparticles with Folic Acid and Biotin for Anticancer Drug Delivery. Pharmaceutics. https://doi.org/10.3390/pharmaceutics13030326