ROS-responsive nanoparticles based on amphiphilic hyperbranched polyphosphoester for drug delivery: Light-triggered size-reducing and enhanced tumor penetration

Up to now, limited tumor penetration and poor therapeutic efficiency of drug-loaded nanoparticles are still the major challenges in nanomedicines for cancer chemotherapy. In photodynamic therapy, photosensitizers are often used to generate cytotoxic reactive oxygen species to kill cancer cells. Here...

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Bibliographic Details
Published in:Biomaterials 2019-08, Vol.211, p.68-80
Main Authors: Jin, Hua, Zhu, Ting, Huang, Xiange, Sun, Mo, Li, Hegen, Zhu, Xinyuan, Liu, Mingliang, Xie, Yibin, Huang, Wei, Yan, Deyue
Format: Article
Language:English
Subjects:
Hyperbranched polyphosphoester
Light-triggered
ROS-Responsive
Size reducing nanoparticle
Tumor penetration
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Summary:Up to now, limited tumor penetration and poor therapeutic efficiency of drug-loaded nanoparticles are still the major challenges in nanomedicines for cancer chemotherapy. In photodynamic therapy, photosensitizers are often used to generate cytotoxic reactive oxygen species to kill cancer cells. Here, we report a kind of ROS-responsive nanoparticles with light-triggered size-reducing for enhanced tumor penetration and in vivo drug delivery to improve therapeutic efficiency. The nanoparticles were constructed by the self-assembly of an amphiphilic hyperbranched polyphosphoester containing thioketal units and photosensitizers, which is synthesized through the self-condensing ring-opening polymerization of a novel cyclic phosphate monomer and then end-capped with photosensitizer Chlorin e6. These nanoparticles have an initial averaged diameter of ∼210 nm, which can be used as drug carriers to load camptothecin with relatively stable in blood circulation. The CPT-loaded nanoparticles can be concentrated in tumor tissues through the long blood circulation and enhanced permeability and retention effect. Upon 660 nm laser irradiation on tumor tissues, the Ce6s in nanoparticles can effectively generate ROS to kill cancer cells meanwhile cleave the thioketal units to sequentially reduce the size of nanoparticles, which facilitate them more efficient tumor penetration with a programmable release of CPT. Both in vitro and in vivo studies confirmed the above results. Such ROS-responsive nanoparticles with light-triggered size-reducing provided a feasible approach to improve drug tumor penetration and achieve satisfied therapeutic efficacy. [Display omitted]
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2019.04.029