nn3c04059_si_001.pdf (1.73 MB)
Amplified Targeted Drug Delivery Independent of Target Number through Alternative Administration of Two Matched Nanoparticles
journal contributionposted on 2023-12-01, 19:00 authored by Mengwen Song, Ruiyuan Cao, Xingjuan Chen, Cui Wang, Xiaowen Xing, Wei Li, Yuexiang Li, Yajin Liao, Wu Zhong, Qihong Li, Zhiqiang Liu
Targeting nanoparticles (NPs) based on the specific binding of ligands with molecular targets provides a promising tool for tissue-selective drug delivery. However, the number of molecular targets on the cell surface is limited, hindering the number of NPs that can bind and, thus, limiting the therapeutic outcome. Although several strategies have been developed to enhance drug delivery, such as enhancing drug loading and circulation time or increasing the enhanced permeability and retention effect of nanocarriers, none have resolved this issue. Herein, we designed a simple method for amplified and targeted drug delivery using two matched NPs. One NP was aptamer-functionalized to specifically bind to target cells, while the other was aptamer-complementary DNA-functionalized to specifically bind to aptamer-NPs. Alternate administration of the two matched NPs enables their continuous accumulation in the disease site despite their limited molecular targets. As a proof of concept, the method was tested in a breast cancer model and significantly enhanced chemotherapy of tumor cells in vitro and in vivo. The potential applications of this method in a brain injury model were also demonstrated. Overall, the study describes a method for amplified targeted drug delivery independent of the target number.
selective drug deliveryenhancing drug loadingenhance drug deliverydisease site despitebreast cancer modelbrain injury modelalthough several strategiessignificantly enhanced chemotherapymolecular targets provideslimited molecular targetsmolecular targetsenhanced permeabilityvivo vitro tumor cellstherapeutic outcometarget cellsstudy describesspecific bindingretention effectpromising toolpotential applicationsone npcontinuous accumulationcomplementary dnacirculation timecell surfacealternative administrationalternate administrationalso demonstrated