Ultralong Circulating Lollipop‐Like Nanoparticles Assembled with Gossypol, Doxorubicin, and Polydopamine via π–π Stacking for Synergistic Tumor Therapy. (14th November 2018)

• Record Type: Journal Article
• Authors: Wang, Ya; Wu, Youshen; Li, Ke; Shen, Shihong; Liu, Zeying; Wu, Daocheng
• Is Part Of: Advanced functional materials. Volume 29:Number 1(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-11-14
• Subjects: π–π stacking -- self‐assembly -- synergistic therapy -- tumor -- ultralong circulating nanoparticles; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adfm.201805582
• Languages: English
• ISSNs: 1616-301X

Abstract

Abstract: Long blood circulation in vivo remains a challenge to dual‐drug‐loaded nanocarriers for synergistic chemotherapy. Herein, a novel strategy to prepare lollipop‐like dual‐drug‐loaded nanoparticles (DOX–PDA–gossypol NPs) is developed based on the self‐assembly of gossypol, doxorubicin (DOX), and polydopamine (PDA) via π–π stacking. Dopamine polymerizes to PDA and fills the gaps between the gossypol and DOX molecules to form the super compact long‐circulating nanoparticles. The DOX–PDA–gossypol NPs show a suitable particle size of 59.6 ± 9.6 nm, high drug loading of 91%, superb stability, high maximum‐tolerated dose (MTD) of over 60 mg kg ‐1, and negligible toxicity. These NPs also exhibit pH‐dependent drug release and low combination index (0.23). Notably, they show dramatically ultralong blood circulation (>192 h) with elimination half times 458‐fold and 258‐fold longer than that of free DOX and free gossypol, respectively. These values are markedly higher than most of the reported results. Therefore, the DOX–PDA–gossypol NPs have a high tumor accumulation of 12% remaining on the 8th day postinjection. This characteristic contributes to the excellent tumor comprehensive synergistic therapeutic efficacy (TIR > 90%) with low administration dosage and is benefitted for widening the drug therapeutic window. Thus, the proposed strategy has remarkable potential for tumor synergistic therapy. Abstract : An efficient strategy is developed to prepare a long‐circulating dual‐drug‐loaded nanocarrier system based on π–π stacking of gossypol, doxorubicin, and polydopamine for synergistic chemotherapy. In this system, polydopamine fills the gaps between the dual‐drug to form lollipop‐like supercompact nanoparticles. The system has the advantages of ultralong blood circulation in vivo, negligible toxicity, and excellent tumor comprehensive synergistic therapeutic efficacy.