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.
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