Tumor targeting antibody-conjugated nanocarrier with pH/thermo dual-responsive macromolecular film layer for enhanced cancer chemotherapy

Jiafeng Zhuang, Lina Zhou, Wen Tang, Tonghao Ma, Hui Li, Xiaoli Wang, Chao Chen, Ping Wang

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

In response to changeful tumor environment, self-targeting antibody-mediated drug nanocarrier with functionalization have been broadly developed to realize specific antitumor efficacy. In this work, an antibody-conjugated drug delivery system with pH/temperature dual-responsive property was devised and fabricated based on mesoporous silica nanoparticle (MSN). Briefly, MSN was first modified with the pH/temperature dual-responsive macromolecular copolymer P(NIPAm-co-MAA) via a precipitation polymerization method, and then grafted with the anti-human epidermal growth factor receptor 2 (HER2) single chain antibody fragment (scFv) to specifically target HER2 positive breast cancer cells. With this structure, such targeting nanoparticles eventually exhibited high drug loading capacity and good biocompatibility. Meanwhile, the cumulative in vitro drug release profile displayed a low-level early leakage at neutral pH values/low temperature while remarkably enhanced release at an acidic pH value/high temperature, indicating an apparent pH/temperature-triggered drug release pattern. Moreover, tumor-targeting assay revealed that the anti-HER2 scFv-surface decoration greatly enhanced the cellular uptake of as-prepared nanoparticle through HER2-antibody-mediated endocytosis, as well as improved the uptake selectivity between normal and cancer cells. More importantly, both the in vitro and in vivo anticancer experiments indicated that such targeting dual-responsive nanoplatform could efficiently inhibit the growth of HER2 positive breast cancer with minimal side effects. Collectively, all these results promised such specific-targeted and dual-responsive nanoparticle a smart drug delivery system, and it provided a promising perspective in efficient and controllable cancer therapeutic application.

Original languageEnglish (US)
Article number111361
JournalMaterials Science and Engineering C
Volume118
DOIs
StatePublished - Jan 2021

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 “Super Postdoctoral” Incentive Plan , and the Open Funding Project of the State Key Laboratory of Bioreactor Engineering .

Publisher Copyright:
© 2020 Elsevier B.V.

Keywords

  • HER2 targeting
  • Mesoporous silica nanoparticle
  • pH/temperature dual-responsive

PubMed: MeSH publication types

  • Journal Article

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