Controlled siRNA Release of Nanopolyplex for Effective Targeted Anticancer Therapy in Animal Model
© 2024 Jia et al..
Introduction: Spatiotemporally controlled release of siRNA for anti-tumor therapy poses significant challenges. Near-infrared (NIR) light, known for its exceptional tissue penetration and minimal tissue invasiveness, holds promise as a viable exogenous stimulus for inducing controlled siRNA release in vivo. However, the majority of light-responsive chemical bonds exhibit absorption wavelengths in the ultraviolet (UV) or short-wavelength visible light range.
Methods: To achieve NIR-controlled siRNA release, the study synthesized a UV-sensitive triblock copolymer cRGD-poly(ethylene glycol)-b-poly(aspartic acid ester-5-(2'-(dimethylamino)ethoxy)-2-nitrobenzyl alcohol)-b-polyphenylalanine, abbreviated as cRGD-PEG-PAsp(EDONB)-PPHE. This copolymer is composed of a cRGD-capped PEG block (cRGD-PEG), a poly(aspartate) block modified with cationic moieties through UV-cleavable 2-nitrobenzyl ester bonds [PAsp(EDONB)], and a hydrophobic polyphenylalanine block (PPHE). The cationic amphiphilic polymer cRGD-PEG-PAsp(EDONB)-PPHE can assemble with hydrophobic upconversion nanoparticles (UCNPs) to form a cationic micelle designated as T-UCNP, which subsequently complexes with siRNA to create the final nanopolyplex T-si/UCNP. siRNA-PLK1 was employed to prepare T-PLK1/UCNP nanopolyplex for anti-tumor therapy.
Results: T-PLK1/UCNP not only exhibited outstanding tumor cell targeting through cRGD modification but also achieved 980 nm NIR-controlled PLK1 gene silencing. This was achieved by utilizing the encapsulated UCNPs to convert NIR into UV light, facilitating the cleavage of 2-nitrobenzyl ester bonds. As a result, there was a significant suppression of tumor growth.
Conclusion: The UCNPs-encapsulated nanopolyplex T-si/UCNP, capable of co-delivering siRNA and UCNPs, enables precise NIR-controlled release of siRNA at the tumor site for cancer RNAi therapy. This nanopolyplex can enhance the controllability and safety of RNAi therapy for tumors, and it also holds the potential to serve as a platform for achieving controlled release and activation of other drugs, such as mRNA and DNA.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:19 |
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| Enthalten in: |
International journal of nanomedicine - 19(2024) vom: 22., Seite 1145-1161 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Jia, Jingchao [VerfasserIn] |
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| Links: |
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| Themen: |
Anti-tumor therapy |
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| Anmerkungen: |
Date Completed 14.02.2024 Date Revised 14.02.2024 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.2147/IJN.S443636 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM368345912 |
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| 245 | 1 | 0 | |a Controlled siRNA Release of Nanopolyplex for Effective Targeted Anticancer Therapy in Animal Model |
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| 520 | |a Introduction: Spatiotemporally controlled release of siRNA for anti-tumor therapy poses significant challenges. Near-infrared (NIR) light, known for its exceptional tissue penetration and minimal tissue invasiveness, holds promise as a viable exogenous stimulus for inducing controlled siRNA release in vivo. However, the majority of light-responsive chemical bonds exhibit absorption wavelengths in the ultraviolet (UV) or short-wavelength visible light range | ||
| 520 | |a Methods: To achieve NIR-controlled siRNA release, the study synthesized a UV-sensitive triblock copolymer cRGD-poly(ethylene glycol)-b-poly(aspartic acid ester-5-(2'-(dimethylamino)ethoxy)-2-nitrobenzyl alcohol)-b-polyphenylalanine, abbreviated as cRGD-PEG-PAsp(EDONB)-PPHE. This copolymer is composed of a cRGD-capped PEG block (cRGD-PEG), a poly(aspartate) block modified with cationic moieties through UV-cleavable 2-nitrobenzyl ester bonds [PAsp(EDONB)], and a hydrophobic polyphenylalanine block (PPHE). The cationic amphiphilic polymer cRGD-PEG-PAsp(EDONB)-PPHE can assemble with hydrophobic upconversion nanoparticles (UCNPs) to form a cationic micelle designated as T-UCNP, which subsequently complexes with siRNA to create the final nanopolyplex T-si/UCNP. siRNA-PLK1 was employed to prepare T-PLK1/UCNP nanopolyplex for anti-tumor therapy | ||
| 520 | |a Results: T-PLK1/UCNP not only exhibited outstanding tumor cell targeting through cRGD modification but also achieved 980 nm NIR-controlled PLK1 gene silencing. This was achieved by utilizing the encapsulated UCNPs to convert NIR into UV light, facilitating the cleavage of 2-nitrobenzyl ester bonds. As a result, there was a significant suppression of tumor growth | ||
| 520 | |a Conclusion: The UCNPs-encapsulated nanopolyplex T-si/UCNP, capable of co-delivering siRNA and UCNPs, enables precise NIR-controlled release of siRNA at the tumor site for cancer RNAi therapy. This nanopolyplex can enhance the controllability and safety of RNAi therapy for tumors, and it also holds the potential to serve as a platform for achieving controlled release and activation of other drugs, such as mRNA and DNA | ||
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| 700 | 1 | |a Tang, Xiaodong |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Shuanghai |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Li |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Jifeng |e verfasserin |4 aut | |
| 700 | 1 | |a Kuang, Yuting |e verfasserin |4 aut | |
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