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T7 peptide-modified erythrocyte membrane-camouflaged amphiphilic self-delivery biomimetic nanodrug for targeting therapy oral squamous cell carcinoma

Year: 2025

Type: article

Abstract: Oral squamous cell carcinoma (OSCC) is a common oral malignancy. However, conventional chemotherapeutic strategies present many limitations. To overcome these challenges, a cell membrane-camouflaged amphiphilic self-delivery nano-prodrug was developed for the targeted treatment of OSCC. In this system, the hydrophobic anticancer drug methotrexate (MTX) and the hydrophilic drug gemcitabine (GEM) were conjugated via amide bonds to form an amphiphilic drug-drug conjugate (ADDC), which self-assembled into nanoparticles (MG NPs). Phospholipids were modified with T7 peptide, capable of targeting the highly expressed transferrin receptor (TFR) on tumor cell surfaces, and subsequently loaded onto red blood cell membranes (RBCM) to prepare T7 peptide-modified RBCM (T7-RBCM). The MG NPs were then encapsulated with T7-RBCM by co-extrusion to form T7-RBCM@MG NPs. In vitro studies demonstrated that T7-RBCM@MG NPs were more efficiently internalized by tumor cells due to specific recognition between the T7 peptide and TFR, exhibited stronger inhibitory activity against SCC-7 cells, and significantly induced apoptosis. In vivo experiments confirmed that T7-RBCM@MG NPs exhibited favourable biosafety, prolonged circulation, and enhanced tumor-targeting delivery, resulting in significant tumor growth inhibition without notable toxicity to major organs. • The design of a dual-drug amphiphilic conjugate: Hydrophobic methotrexate (MTX) and hydrophilic gemcitabine (GEM) were conjugated via amide bonds to form an amphiphilic drug-drug conjugate (ADDC), which self-assembled into nanoparticles (MG NPs). This eliminated the need for additional carriers, improving drug stability and synergistic effects. • T7 peptide-modified RBCM camouflage: T7-modified RBCM was used to coat MG NPs. The T7 peptide specifically targets TFR overexpressed on tumor cells, enabling active targeting. Meanwhile, CD47 protein on RBCM provides a “don’t eat me” signal, allowing prolonged circulation, enhanced tumor targeting, and extended drug action. • Potent tumor inhibitory activity: In vitro experiments on SCC-7 cells demonstrated that T7-RBCM@MG NPs significantly inhibited tumor growth, reducing the IC50 value to 7.49 ± 1.38 μg/mL, nearly threefold lower than free MTX. Furthermore, apoptosis was significantly induced, with an apoptosis rate of 39.47 ± 2.77%. • Precise tumor targeting: In a tumor-bearing mouse model, T7-RBCM@DiD NPs exhibited markedly higher fluorescence intensity at tumor sites compared with RBCM@DiD NPs and DiD NPs. The fluorescence signal of T7-RBCM@DiD NPs was about 2.9-fold and 3.1-fold stronger than that of RBCM@DiD NPs and DiD NPs, respectively.

Source: Materials Today Bio

DOI: 10.1016/j.mtbio.2025.102345

Authors: Yun Deng, Wangxiang Yan, Dalong Shu, Li Zhu, Songling Chen, Yu Chen

Institutions: The First Affiliated Hospital, Sun Yat-sen University, Chongqing University

Language: English

Topic: Nanoparticle-Based Drug Delivery

Subfield: Biomaterials

Field: Materials Science

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,400