Theranostics 2019; 9(10):2897-2909. doi:10.7150/thno.33534 This issue

Research Paper

Nano-drug System Based on Hierarchical Drug Release for Deep Localized/Systematic Cascade Tumor Therapy Stimulating Antitumor Immune Responses

Yuchu He1,2, Cong Cong1, Xiaoling Li1, Ruiyan Zhu1,3, Anshuo Li4, Shuxian Zhao1, Xiaowei Li1, Xin Cheng1, Mengxue Yang1, Dawei Gao1,2✉

1. Applyied Chemistry Key Laboratory of Hebei Province, Department of Bioengineering, Yanshan University, No.438 Hebei Street, Qinhuangdao, 066004, China.
2. State Key Laboratory of Metastable Materials Science and Technology, Yanshan University, Qinhuangdao 066004, P. R. China.
3. Hebei Province Asparagus Industry Technology Research Institute, Qinhuangdao, 066004, China.
4. Department of Prosthodontics Ninth People's Hospital Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( See for full terms and conditions.
He Y, Cong C, Li X, Zhu R, Li A, Zhao S, Li X, Cheng X, Yang M, Gao D. Nano-drug System Based on Hierarchical Drug Release for Deep Localized/Systematic Cascade Tumor Therapy Stimulating Antitumor Immune Responses. Theranostics 2019; 9(10):2897-2909. doi:10.7150/thno.33534. Available from

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Graphic abstract

Inaccessibility of deep-seated malignant cells in the central region of tumors and uncontrollable tumor recurrence represent a significant challenge for conventional synergistic cancer therapy. Herein, we designed a novel nanoplatform based on hierarchical drug release for deep cascade cancer therapy including localized photothermal therapy, systematic chemotherapy, and elicited immune responses.

Methods: The first-step chemotherapy could be carried out by polydopamine (PDA) releasing doxorubicin (DOX) in the specific microenvironment of lysosomes (pH 5.5). The branched gold nanoshells and PDA converted the light to heat efficiently to accomplish the second-step photothermal therapy and collapsed biomimetic vesicles (BVs) to release paclitaxel (PTX), which promoted the third-step of chemotherapy and triggered immune responses.

Results: After 10 days of treatment, there were no obvious residual tumors in tumor-bearing mice. Significantly, 10 days after stopping treatment, mice in the drug immune-therapeutic group showed little tumor recurrence (1.5 times) compared to substantial recurrence (20 times) in the conventional treatment group.

Conclusion: The hierarchical drug release and cascade therapeutic modality enhance the penetration of drugs deep into the tumor tissue and effectively inhibit recurrence. This cascade therapeutic modality provides a novel approach for more effective cancer therapy.

Keywords: Hierarchical drug release, Tumor recurrence, Biomimetic vesicles, Cascade cancer therapy, Immune responses