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Controlled siRNA Release of Nanopolyplex for Effective Targeted Anticancer Therapy in Animal Model.
Jia, Jingchao; Yang, Jing; Qian, Leimin; Zhou, Biao; Tang, Xiaodong; Liu, Shuanghai; Wu, Li; Chen, Jifeng; Kuang, Yuting.
Afiliación
  • Jia J; Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.
  • Yang J; Department of General Surgery, Jiangyin Hospital Affiliated to Nantong University, Wuxi, People's Republic of China.
  • Qian L; Jiangnan University Medical Center, Wuxi, People's Republic of China.
  • Zhou B; Department of General Surgery, Jiangyin Hospital Affiliated to Nantong University, Wuxi, People's Republic of China.
  • Tang X; Department of General Surgery, Jiangyin Hospital Affiliated to Nantong University, Wuxi, People's Republic of China.
  • Liu S; Department of General Surgery, Jiangyin Hospital Affiliated to Nantong University, Wuxi, People's Republic of China.
  • Wu L; Department of General Surgery, Jiangyin Hospital Affiliated to Nantong University, Wuxi, People's Republic of China.
  • Chen J; Department of Pharmaceutics, People's Hospital of Shanggao, Yichun, People's Republic of China.
  • Kuang Y; The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, Jinan University, Guangzhou, People's Republic of China.
Int J Nanomedicine ; 19: 1145-1161, 2024.
Article en En | MEDLINE | ID: mdl-38344438
ABSTRACT

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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Nanopartículas / Neoplasias Límite: Animals Idioma: En Revista: Int J Nanomedicine Año: 2024 Tipo del documento: Article Pais de publicación: Nueva Zelanda
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Nanopartículas / Neoplasias Límite: Animals Idioma: En Revista: Int J Nanomedicine Año: 2024 Tipo del documento: Article Pais de publicación: Nueva Zelanda