Details

Autor(en) / Beteiligte

• Feng, Liandong
• Chen, Zhiyou
• Dong, Wei
• Xie, Aming
• Zang, Xiaowei
• Li, Juan

Titel

An intracellular in situ assembly of ultrasmall nanoparticles as drug depots for enhanced chemotherapy

Ist Teil von

• New journal of chemistry, 2023-12, Vol.47 (47), p.21960-21968

Ort / Verlag

Cambridge: Royal Society of Chemistry

Erscheinungsjahr

2023

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• The poor tumour accumulation of nanoparticles (NPs) severely hampers the therapeutic efficacy of NPs, which is mainly attributed to the inadequate drug distribution within tumour tissues. Developing an intracellular in situ assembling system (IIAS) that can form micro-sized aggregations as drug depots for the prolonged retention of drugs inside tumour cells and deeply penetrate tumour tissues owing to the initial small size of the NPs is a promising strategy for enhancing the tumour accumulation of drugs and improving their chemotherapeutic efficacy. Herein, smart in situ assembling nanoparticles (named DOX-uNPs) with an ultrasmall size of approximately 8 nm were prepared by encapsulating doxorubicin (DOX) into the hydrophobic domains of human serum albumin (HSA). After extravasating into tumour cells, the DOX-uNPs aggregated into micro-sized particles as drug depots through a thio-disulfide exchange reaction between neighboring nanoparticles triggered by the elevated level of reduced glutathione (GSH) to achieve the sustained release of DOX, which was visually confirmed by the fluorescent imaging of the sections of tumours after systemic administration. Furthermore, the in vivo anti-lymphoma results of the DOX-uNPs demonstrated a dramatic tumour reduction of approximately 71% when compared with free DOX. Thus, this smart in situ aggregating nanoparticles system provides a promising nanoplatform for both deep tumour penetration and prolonged tumour retention, which is a robust strategy for higher tumour accumulation of intracellular targeted drugs for enhanced therapeutic efficacy.