Journal
THERANOSTICS
Volume 12, Issue 2, Pages 944-962Publisher
IVYSPRING INT PUBL
DOI: 10.7150/thno.67572
Keywords
chemodynamic therapy; one-pot strategy; tumor-specific; GSH depletion; self-amplified therapy
Categories
Funding
- National Key Research and Development Program of China [2020YFA0211200, 2020YFA0710700, 2018YFA 0208900]
- National Science Foundation of China [31972927, 82172757]
- Scientific Research Foundation of Huazhong University of Science and Technology [3004170130]
- Program for HUST Academic Frontier Youth Team [2018QYTD01]
- HCP Program for HUST
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This study developed an intelligent nanoplatform that can activate chemodynamic therapy specifically in tumor tissues and provide photoacoustic imaging and amplified combined therapy. The nanoplatform releases therapeutic drugs through interactions with the tumor microenvironment and induces intratumoral oxidative stress. Additionally, the nanoplatform exhibits good biosafety.
Rationale: Chemodynamic therapy (CDT) is an emerging tumor-specific therapeutic strategy. However, the anticancer activity of CDT is impeded by the insufficient Fenton catalytic efficiency and the high concentration of glutathione (GSH) in the tumor cells. Also, it is challenging to eliminate tumors with CDT alone. Thus, simple strategies aimed at constructing well-designed nanomedicines that can improve therapeutic efficiency of CDT and simultaneously incorporate extra therapeutic modes as helper are meaningful and highly required. Method: Tailored to specific features of tumor microenvironment (TME), in this study, we developed a biosafe, stable and TME-activated theranostic nanoplatform (P(HSD-Cu-DA)) for photoacoustic imaging (PAI) and self-amplified cooperative therapy. This intelligent nanoplatform was fabricated following a simple one-pot coordination and polymerization strategy by using dopamine and Cu2+ as precursors and redox-responsive hydroxyethyl starch prod rugs (HES-SS-DOX) as stabilizer. Results: Interestingly, the pre-doped Cu2+ in polydopamine (PDA) framework can endow P(HSD-Cu-DA) NPs with tumor-specific CDT ability and remarkably enhance NIR absorption of PDA. PAI and biodistribution tests proved such nanoplatform can effectively accumulate in tumor tissues. Following enrichment, massive amounts of toxic hydroxyl radicals (OH, for CDT) and free DOX (for chemotherapy) were generated by the stimulation of TME, which was further boosted by local hyperthermia. Concomitantly, in the process of activating these therapeutic functions, GSH depletion triggered by disulfide bond (-SS-) breakage and Cu2+ reduction within tumor cells occurred, further amplifying intratumoral oxidative stress. Importantly, the framework structure dominated by bioinspi red polydopamine and clinical-used HES guaranteed the long-term biosafety of in vivo treatment. As a result, the mutual promotion among different components yields a potent tumor suppression outcome and minimized systemic toxicity, with one dosage of drug administration and laser irradiation, respectively. Conclusion: This work provides novel insights into designing efficient and tumor-specific activatable nanotherapeutics with significant clinical translational potential for cancer therapy.
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