Abstract
Currently, single chemotherapeutics or photosensitizers implemented in clinic present huge challenges in terms of unfavorable therapeutic efficacy, physiological instability and non-selective toxicity. In order to remedy the faultiness of insufficient efficiency of monotherapy, we herein synthesized an “all-in-one” targeting drug delivery system with multimodal therapy based on chemo-photodynamic synergistic therapy. Specifically, mesoporous silica nanorods were first synthesized through doping chlorin e6 (Ce6) in the sol–gel process, and then were used to load chemotherapy drug. After the amino groups and boronic acid groups were sequentially modified on the surface of nanoparticles, lactobionic acid (LA) was chosen as an intermediary to achieve simultaneous crosslinking of targeting agent LA and sealing agent sericin through pH responsive boronic ester linkage. The obtained ultimate nanocomposites possessed good biocompatibility, colloidal stability and hemocompatibility. Besides, in vitro endocytosis experiment performed with confocal laser scanning microscopy and flow cytometry testified the LA-mediated accurate tumor-specific targeting ability of synthesized nanocarriers. Moreover, a series of in vitro assays demonstrated that fabricated therapeutic nanoplatform could not only release loaded drugs in response to acidic environment to achieve chemotherapy, but also could generate singlet oxygen from photosensitizer Ce6 under external light stimulation to realize photodynamic therapy. Most interestingly, the combination therapy including photodynamic therapy and chemotherapy exhibited a synergistic effect against tumor cells in both in vivo and ex vivo experiments. Briefly, the drug delivery system reported here could attain effective chemo-photodynamic synergistic therapy to dispose of the insufficient lethality of monotherapy while guaranteeing the safety during in vivo application.
| Original language | English (US) |
|---|---|
| Article number | 130536 |
| Journal | Chemical Engineering Journal |
| Volume | 424 |
| DOIs | |
| State | Published - Nov 15 2021 |
Bibliographical note
Funding Information:This work was sponsored by the National Natural Science Foundation of China (Nos. 21908059, 41907318 and 21636003), the China Postdoctoral Science Foundation (No. 2019M651419), Shanghai Sailing Program (No. 19YF1410900), the Fundamental Research Funds for the Central Universities (No. 22221818014), the Shanghai Post-doctoral Excellence Program (No. 2018011), the Open Funding Project of the State Key Laboratory of Bioreactor Engineering, and the Project Supported by the Foundation (No. GZKF202031) of State Key Laboratory of Biobased Material and Green Papermaking, Qilu University of Technology, Shandong Academy of Sciences. All animal experiments were conducted in accordance with Chinese legislation on the Use and Care of Research Animals (Document No. 55, 2001), and institutional guidelines for the Care and Use of Laboratory Animals established by the East China University of Science and Technology Animal Studies Committee, and this committee approved the experiments.
Funding Information:
This work was sponsored by the National Natural Science Foundation of China (Nos. 21908059 , 41907318 and 21636003 ), the China Postdoctoral Science Foundation (No. 2019M651419 ), Shanghai Sailing Program (No. 19YF1410900 ), the Fundamental Research Funds for the Central Universities (No. 22221818014 ), the Shanghai Post-doctoral Excellence Program (No. 2018011), the Open Funding Project of the State Key Laboratory of Bioreactor Engineering , and the Project Supported by the Foundation (No. GZKF202031 ) of State Key Laboratory of Biobased Material and Green Papermaking, Qilu University of Technology, Shandong Academy of Sciences .
Publisher Copyright:
© 2021 Elsevier B.V.
Keywords
- Ce6-doped nanoparticle
- Chemo-photodynamic synergistic therapy
- Drug delivery
- Dual response
- Tumor targeting