Cetin Ersen Busra, Goncu Beyza, Dag Aydan, Birlik Demirel Gokcen
Institute of Graduate Programs and Department of Chemistry, Polatlı Faculty of Arts and Sciences, Ankara Hacı Bayram Veli University, Ankara 06900, Turkey.
Experimental Research Center, Bezmialem Vakif University, İstanbul 34093, Turkey.
ACS Appl Mater Interfaces. 2023 Feb 13. doi: 10.1021/acsami.2c21180.
The combination of multimodal therapies into one nanocarrier system is promising for its potential to enhance treatment performance by overcoming the efficacy problems encountered in conventional monomodal therapy. In this study, targeted and multimodal therapeutic hybrid nanocarriers are fabricated for breast cancer treatments. In this context, the synthesized gold nanorods (AuNRd), photothermal therapy (PTT) agent, are coated with doxorubicin (DOX) conjugated, targeted, and biocompatible tetrablock glycopeptide (P(DMAEMA--HMBAMA--FrucMA)--P(Lys)/DOX, P-DOX) polymer. Here, fructose-based (Fruc) glycopeptide polymer enhances cellular uptake into breast cancer through GLUT5. A photosensitizer molecule, indocyanine green (ICG), was loaded into the particles to provide photodynamic therapy (PDT) upon NIR light at 808 nm. In the final step of the fabrication, the polymer-coated nanoparticles are integrated with antisense ISIS5132 oligonucleotides to prevent apoptotic resistance of cells against drug molecules. The biocompatibility and therapeutic efficacy of the nanoparticles are evaluated on both human normal skin fibroblast cell (CCD-1079Sk) and human breast cancer cell (MCF7) lines. These multimodal therapeutic AuNRd@P-DOX/ICG/ISIS5132 nanoparticles demonstrate an efficient triple synergistic effect of chemo-/PTT/PDT, which is desired for breast cancer treatment. We believe that this promising multimodal therapeutic nanoparticle system can promote the further clinical application in the treatment of breast cancer and can also be adapted to other types of cancer.
将多种治疗方式整合到一个纳米载体系统中，有望克服传统单模态治疗中遇到的疗效问题，从而提高治疗效果。在本研究中，制备了用于乳腺癌治疗的靶向多模态治疗性杂化纳米载体。在此背景下，将合成的金纳米棒（AuNRd），即光热治疗（PTT）剂，用与阿霉素（DOX）偶联的、靶向且生物相容的四嵌段糖肽（P(DMAEMA-HMBAMA-FrucMA)-P(Lys)/DOX，P-DOX）聚合物进行包覆。在此，基于果糖（Fruc）的糖肽聚合物通过GLUT5增强对乳腺癌细胞的摄取。将一种光敏剂分子吲哚菁绿（ICG）负载到颗粒中，以便在808 nm的近红外光照射下提供光动力治疗（PDT）。在制备的最后一步，将聚合物包覆的纳米颗粒与反义ISIS5132寡核苷酸整合，以防止细胞对药物分子产生凋亡抗性。在人正常皮肤成纤维细胞系（CCD-1079Sk）和人乳腺癌细胞系（MCF7）上评估了纳米颗粒的生物相容性和治疗效果。这些多模态治疗性AuNRd@P-DOX/ICG/ISIS5132纳米颗粒展现出化疗/光热治疗/光动力治疗的高效三联协同效应，这正是乳腺癌治疗所期望的。我们相信，这种有前景的多模态治疗性纳米颗粒系统能够促进乳腺癌治疗的进一步临床应用，并且也可适用于其他类型的癌症。
