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Vascular-confined multi-passage discoidal nanoconstructs for the low-dose docetaxel inhibition of triple-negative breast cancer growth

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Nano Research 2022年第1期15卷 482-491页

作者： Alessia Felici daniele di mascolo Miguel Ferreira Simone Lauciello Luca Bono Andrea Armirotti Arunkumar Pitchaimani Anna Lisa Palange Paolo Decuzzi Laboratory of Nanotechnology for Precision Medicine Fondazione Istituto Italiano di TecnologiaGenoa 16163Italy Department of Informatics BioengineeringRobotics and System EngineeringUniversity of GenoaGenoa 16126Italy Nanochemistry Laboratory Fondazione Istituto Italiano di TecnologiaGenoa 16163Italy Analytical Chemistry Laboratory Fondazione Istituto Italiano di TecnologiaGenoa 16163Italy

Taxane efficacy in triple negative breast cancer(TNBC)is limited by insufficient tumor accumulation and severe off-target *** offer a unique opportunity to enhance the anti-cancer potency of this ***,1,000 nm×400 nm discoidal polymeric nanoconstructs(DPN)encapsulating docetaxel(DTXL)and the near infrared compound Iipid-Cy5 were *** were obtained by filling multiple times cylindrical wells in a poly(vinyl alcohol)template with a polymer mixture comprising poly(lactic-co-glycolic acid)(PLGA)and poly(ethylene glycol)diacrylate(PEG-DA)chains together with therapeutic and imaging *** resulting“multi-passage”DPN exhibited higher DTXL loading,Iipid-Cy5 stability,and stiffness as compared to the conventional"single-passage"*** microscopy confirmed that DTXL-DPN were not taken up by MDA-MB-231 cells but would rather sit next to the cell membrane and slowly release DTXL *** DPN had no toxicity on TNBC cells,whereas DTXL-DPN presented a cytotoxic potential comparable to free DTXL(IC_(50)=2.6 nM±1.0 nM vs.7.0 nM±1.09 nM at 72 h).In orthotopic murine models,DPN accumulated in TNBC more efficiently than *** only 2 mg/kg DTXL,intravenously administered every 2 days for a total of 13 treatments,DTXL-DPN induced tumor regression and were associated to an overall 80%survival rate as opposed to a 30%survival rate for free-DTXL,at 120 *** untreated mice succumbed before 90 ***,this data demonstrates that vascular confined multi-passage DPN,biomimicking the behavior of circulating platelets,can efficiently deliver chemotherapeutic molecules to malignant tissues and effectively treat orthotopic TNBC at minimal taxane doses.

关键词： hydrogel particles template strategy vascular targeting biomimicry cancer therapy

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