A size-tunable and multi-responsive nanoplatform for deep tumor penetration and targeted combinatorial radio-/chemotherapy. Issue 29 (10th July 2019)

• Record Type: Journal Article
• Authors: Dahmani, Fatima Zohra; Zhong, Danni; Qi, Yuchen; Dahmani, Aboubaker El G.; Xie, Tingting; Zhou, Bo; Li, Wanli; Yao, Ke; Li, Lei; Zhou, Min
• Is Part Of: Journal of materials chemistry. Volume 7:Issue 29(2019)
• Page Start: 4484
• Page End: 4498
• Publication Date: 2019-07-10
• Subjects: Materials -- Periodicals; Chemistry, Analytic -- Periodicals; Biomedical materials -- Research -- Periodicals; 543.0284
• DOI: 10.1039/c9tb00716d
• Languages: English
• ISSNs: 2050-750X

Abstract

Abstract : We report a versatile nanoplatform with size tunability, pH-responsiveness, active targeting and radio-/chemotherapeutic features as an efficient tool for tumor therapy. Abstract : Nowadays, the design of multistimuli-responsive and deep penetrating nanotherapeutics remains an auspicious means for improving the efficiency of anticancer therapeutics. Herein, we develop a targeted size-tunable nanosystem that would concurrently and uniformly release its therapeutic cargo into tumor cells by exploiting both extracellular and intracellular signals. This nanosystem (HPDAu) is composed of self-assembled pH-responsive DOX–PAMAM (PD) conjugates and ultrasmall PAMAM-stabilized gold nanoparticles (AuNPs), incorporated into a hyaluronidase-responsive hyaluronic acid nanoshell. HPDAu nanoparticles with an initial particle size of ∼100 nm could disassemble into tiny cationic nanostructures (∼5 nm, PD and AuNPs) upon incubation with HAase, and showed a burst drug-release under tumor microenvironment-mimicking conditions (HAase and acidic conditions). Such characteristics resulted in significantly improved tumor penetration both in vitro and in vivo, along with a higher cellular uptake efficiency and tumor accumulation as compared to free drug solutions. Taking advantage of these features along with the chemotherapeutic effect (DOX) and AuNP/DOX-induced radiosensitization, HPDAu plus radiotherapy (RT) treatment resulted in a substantial increase of apoptotic and cytotoxic effects against 4T1 cells. More importantly, the radio-/chemotherapeutic feasibility of HPDAu was further validated in a 4T1 orthotropic model, revealing a prominent antitumor efficacy and reduced side-toxicity compared to monotherapy and free drug solutions. Therefore, this versatile nanoplatform with active targeting, size tunability and radio-/chemotherapeutic features could be a promising tool for tumor combinatorial therapy.