ID | 61699 |
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Lim, Melissa Siaw Han
Nishiyama, Yuki
Ohtsuki, Takashi
Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
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Watanabe, Kazunori
Graduate School of Natural Science and Technology, Okayama University
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Abstract | The A3B-type Lactosome comprised of poly(sarcosine)3-block-poly(l-lactic acid), a biocompatible and biodegradable polymeric nanomicelle, was reported to accumulate in tumors in vivo via the enhanced permeability and retention (EPR) effect. Recently, the cellular uptake of Lactosome particles was enhanced through the incorporation of a cell-penetrating peptide (CPP), L7EB1. However, the ability of Lactosome as a drug delivery carrier has not been established. Herein, we have developed a method to conjugate the A3B-type Lactosome with ATP-binding cassette transporter G2 (ABCG2) siRNA for inducing in vitro apoptosis in the cancer cell lines PANC-1 and NCI-H226. The L7EB1 peptide facilitates the cellular uptake efficiency of Lactosome but does not deliver siRNA into cytosol. To establish the photoinduced cytosolic dispersion of siRNA, a photosensitizer loaded L7EB1-Lactosome was prepared, and the photosensitizer 5,10,15,20-tetra-kis(pentafluorophenyl)porphyrin (TPFPP) showed superiority in photoinduced cytosolic dispersion. We exploited the combined effects of enhanced cellular uptake by L7EB1 and photoinduced endosomal escape by TPFPP to efficiently deliver ABCG2 siRNA into the cytosol for gene silencing. Moreover, the silencing of ABCG2, a protoporphyrin IX (PpIX) transporter, also mediated photoinduced cell death via 5-aminolevulinic acid (ALA)-mediated PpIX accumulated photodynamic therapy (PDT). The synergistic capability of the L7EB1/TPFPP/siRNA-Lactosome complex enabled both gene silencing and PDT.
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Keywords | Lactosome
ABCG2
siRNA
Cancer
siRNA delivery
Photodynamic therapy
Polymeric micelle
Photosensitizer
Photochemical internalization
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Note | ©2021 Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 License. http://creativecommons.org/licenses/by-nc-nd/4.0/.
This is the accepted manuscript version. The formal published version is available at [https://doi.org/10.1016/j.xphs.2021.01.026] .
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Published Date | 2021-04-30
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Publication Title |
Journal of Pharmaceutical Sciences
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Volume | volume110
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Publisher | Elsevier
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Start Page | 1788
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End Page | 1798
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ISSN | 00223549
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NCID | AA00704450
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Content Type |
Journal Article
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language |
English
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OAI-PMH Set |
岡山大学
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File Version | author
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Related Url | isVersionOf https://doi.org/10.1016/j.xphs.2021.01.026
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Open Access (Publisher) |
non-OA
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Non-OpenArchive
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