Yeast cell membrane-camouflaged PLGA nanoparticle platform for enhanced cancer therapy

• Published in: Journal of controlled release 2023-07, Vol.359, p.347-358
• Main Authors: He, Yu, Chen, Qi-Wen, Yu, Jin-Xin, Qin, Si-Yong, Liu, Wen-Long, Ma, Yi-Han, Chen, Xiao-Sui, Zhang, Ai-Qing, Zhang, Xian-Zheng, Cheng, Yin-Jia
• Format: Article
• Language: English
• Subjects: biomimetics; cancer therapy; cell death; chitosan; colon; Colorectal cancer therapy; colorectal neoplasms; drug therapy; drugs; fluorescence; growth retardation; ileum; nanoparticles; neoplasm cells; Oral drug delivery system; oral gavage; PLGA; Temozolomide; Tumor-specific accumulation; Yeast shell wall; yeasts
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2023.05.043

Temozolomide (TMZ) is an oral DNA-alkylating drug used in colorectal cancer (CRC) chemotherapy. In this work, we proposed a safe and biomimetic platform for macrophages-targeted delivery of TMZ and O6-benzylguanine (O6-BG). TMZ was loaded in poly (D, l-lactide-coglycolide) (PLGA) nanoparticles, followed by sequential coating with O6-BG-grafted chitosan (BG-CS) layers and yeast shell walls (YSW) via layer-by-layer assembly (LBL) process, forming TMZ@P-BG/YSW biohybrids. Due to the yeast cell membrane-camouflage, TMZ@P-BG/YSW particles exhibited significantly enhanced colloidal stability as well as low premature drug leakage in simulated gastrointestinal conditions. In vitro drug release profiles of TMZ@P-BG/YSW particles revealed noticeable higher TMZ release in simulated tumor acidic environment within 72 h. Meanwhile, O6-BG could down-regulate MGMT expression in CT26 colon carcinoma cells, ultimately facilitating TMZ-induced tumor cell death. After oral delivery of yeast cell membrane-camouflaged particles containing fluorescent tracer (Cy5), TMZ@P-BG/YSW and bare YSW displayed high retention time of 12 h in the colon and small intestine (ileum). Correspondingly, oral gavage administration of TMZ@P-BG/YSW particles afforded favorable tumor-specific retention and superior tumor growth inhibition. Overall, TMZ@P-BG/YSW is validated to be a safe, targetable and effective formulation, paving a new avenue towards highly effective and precise treatment of malignancies. PLGA-based bioinspired platform for tumor-specific retention and enhanced colorectal cancer therapy. [Display omitted]