Abstract
Numerous nanocarriers with pH-responsive properties have been designed and fabricated to reduce the adverse side effects of traditional chemotherapeutics, but these traditional nanocarriers are rarely reversible; this may cause "secondary"side effects on normal tissues, because the nanocarriers cannot be sealed again to prevent the leakage of incompletely released drugs after re-entering blood circulation. To overcome these limitations, we report herein the synthesis of a reversibly pH-responsive drug delivery system, which can achieve regulated drug release in a "release-stop-release"manner corresponding to changes in pH. Specifically, poly(tannic acid) as the "gatekeeper"was firstly deposited and polymerized on the surface of mesoporous silica nanoparticles (MSNs) via a modified mussel-inspired method similar to dopamine, and the formed polymer shell can be easily decorated with a targeting ligand HER2 antibody for the selective delivery of drugs to specific cells. The resulting nanocomposites exhibited good colloidal stability, good biocompatibility, high drug loading capacity and accurate HER2 antibody mediated targeting ability. Interestingly, a series of experiments fully demonstrated that the fabricated nanocomposites possessed intelligent reversible pH-responsive controlled release behavior through adjusting the density of the "gatekeeper"under different pH conditions, thereby achieving reversible switching from "on"to "off". Furthermore, in vitro and in vivo experiments verified that the fabricated targeting nanoparticles could efficiently inhibit tumor growth with minimal side effects. Meanwhile, these nanocarriers exhibited excellent reusability, in vitro cytotoxicity and minimal in vivo myocardial damage. Collectively, the reversible pH-operated nanovalve on the MSNs constructed here could serve as a nanoplatform to solve the problem of "secondary"side effects caused by residual drugs in irreversible "gatekeeper"systems.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 986-998 |
| Number of pages | 13 |
| Journal | Nanoscale Horizons |
| Volume | 5 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 2020 |
Bibliographical note
Funding Information:This work was sponsored by the National Natural Science Foundation of China (No. 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), and the Open Funding Project of the State Key Laboratory of Bioreactor Engineering. All animal experiments were conducted in conformity with Chinese legislation on the Use and Care of Research Animals (Document No. 55, 2001). This experiment was approved by the East China University of Science and Technology Animal Studies Committee, complying with established institutional guidelines for the Care and Use of Laboratory Animals.
Publisher Copyright:
© 2020 The Royal Society of Chemistry.
