Tóm tắt

In response to changeful tumor environment, self-targeting antibody-mediated drug nanocarrier with functio-nalization have been broadly developed to realize specific antitumor efficacy. In this work, an antibody-con-jugated drug delivery system with pH/temperature dual-responsive property was devised and fabricated basedrnon mesoporous silica nanoparticle (MSN). Briefly, MSN was first modified with the pH/temperature dual-re-sponsive macromolecular copolymer P(NIPAm-co-MAA) viaa precipitation polymerization method, and thenrngrafted with the anti-human epidermal growth factor receptor 2 (HER2) single chain antibody fragment (scFv) tornspecifically target HER2 positive breast cancer cells. With this structure, such targeting nanoparticles eventuallyrnexhibited high drug loading capacity and good biocompatibility. Meanwhile, the cumulativein vitrodrug releasernprofile displayed a low-level early leakage at neutral pH values/low temperature while remarkably enhancedrnrelease at an acidic pH value/high temperature, indicating an apparent pH/temperature-triggered drug releasernpattern. Moreover, tumor-targeting assay revealed that the anti-HER2 scFv-surface decoration greatly enhancedrnthe cellular uptake of as-prepared nanoparticle through HER2-antibody-mediated endocytosis, as well as im-proved the uptake selectivity between normal and cancer cells. More importantly, both thein vitro andin vivornanticancer experiments indicated that such targeting dual-responsive nanoplatform could efficiently inhibit therngrowth of HER2 positive breast cancer with minimal side effects. Collectively, all these results promised suchrnspecific-targeted and dual-responsive nanoparticle a smart drug delivery system, and it provided a promisingrnperspective in efficient and controllable cancer therapeutic application.