Abstract
The integration of multiple functions with organic polymers-based nanoagent holds great potential to potentiate its therapeutic efficacy, but still remains challenges. In the present study, we design and prepare an organic nanoagent with oxygen-evolved and targeted ability for improved phototherapeutic efficacy. The iron ions doped poly diaminopyridine (FeD) is prepared by oxidize polymerization and modified with hyaluronic acid (HA). The obtained FeDH appears uniform morphology and size. Its excellent colloidal stability and biocompatibility are demonstrated. Specifically, the FeDH exhibits catalase-like activity in the presence of hydrogen peroxide. After loading of photosensitizer indocyanine green (ICG), the ICG@FeDH not only demonstrates favorable photothermal effect, but also shows improved generation ability of reactive oxygen species (ROS) under near-infrared laser irradiation. Moreover, the targeted uptake of ICG@FeDH in tumor cells is directly observed. As consequence, the superior phototherapeutic efficacy of the targeted ICG@FeDH over non-targeted counterparts is also confirmed in vitro and in vivo. Hence, the results demonstrate that the developed nanoagent rationally integrates the targeted ability, oxygen-evolved capacity and combined therapy in one system, offering a new paradigm of polymer-based nanomedicine for tumor therapy.
Highlights
Nanomaterials-enabled therapy provides unprecedented opportunities to increase the therapeutic efficacy and specificity of tumor treatments in the past decades [1,2,3]
Roswell Park Memorial Institute (RPMI) 1640, fetal bovine serum (FBS), penicillin–streptomycin, and trypsin were supplied by GIBCO Invitrogen Corp. (USA)
Synthesis and characterization of FeDH As depicted in Scheme 1, the FeD was first prepared by iron ions-initiated polymerization of DAP monomer [37]
Summary
Nanomaterials-enabled therapy provides unprecedented opportunities to increase the therapeutic efficacy and specificity of tumor treatments in the past decades [1,2,3]. As a newly emerged type of nanocarriers, covalent organic polymers still needs to be rationally functionalized for improved therapeutic efficacy. Liu’s group demonstrated nanoscale covalent organic polymers as a biodegradable nanomedicine for combined chemotherapy and photodynamic therapy [24, 25]. Porphyrinic covalent organic polymers have been prepared for photothermal and photodynamic therapy [26]. The hypoxia condition in tumor microenvironment severely hinders the efficacy of oxygen-dependent photodynamic therapy and even causes drug resistance or tumor metastasis [27, 28]. Nanoenzyme, who can mimic the activity of natural catalase, has been widely integrated with nanoagents for oxygen-evolving therapy by catalyzing the decomposition of hydrogen peroxide in tumor microenvironment [29, 30]. The fabrication of covalent organic polymers with catalase-like activity is worthwhile to realize more efficient phototherapy
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