Sequential Modulations of Tumor Vasculature and Stromal Barriers Augment the Active Targeting Efficacy of Antibody‐Modified Nanophotosensitizer in Desmoplastic Ovarian Carcinoma

• Published in: Advanced science 2021-02, Vol.8 (3), p.2002253-n/a
• Main Authors: Yan, Yue, Chen, Binlong, Wang, Zenghui, Yin, Qingqing, Wang, Yaoqi, Wan, Fangjie, Mo, Yulin, Xu, Bo, Zhang, Qiang, Wang, Siling, Wang, Yiguang
• Format: Article
• Language: English
• Subjects: Acids; active tumor targeting; Antibodies; antibody‐modified nanophotosensitizer; Cancer therapies; Chemotherapy; Drug delivery systems; FDA approval; Investigations; Nanoparticles; nonspecific uptake; Photodynamic therapy; Polymers; Radiation therapy; stromal barriers; tumor accumulation; Tumors
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202002253

Active‐targeted nanoparticles are attractive carriers due to their potentials to facilitate specific delivery of drugs into tumor cells while sparing normal cells. However, the therapeutic outcomes of active‐targeted nanomedicines are hampered by the multiple physiological barriers in the tumor microenvironment (TME). Herein, an epidermal growth factor receptor‐targeted ultra‐pH‐sensitive nanophotosensitizer is fabricated, and the regulation of the TME to augment the active targeting ability and therapeutic efficacy is pinpointed. The results reveal that tumor vasculature normalization with thalidomide indiscriminately enhance the tumor accumulation of passive and active targeted nanoparticles, both of which are sequestered in the stromal bed of tumor mass. Whereas, photoablation of stromal cells located in perivascular regions significantly improves the accessibility of antibody‐modified nanophotosensitizer to receptor‐overexpressed cancer cells. After sequential regulation of TME, the antitumor efficacy of antibody‐modified nanophotosensitizer is drastically enhanced through synergistic enhancements of tumor accumulation and cancer cell accessibility of active‐targeted nanoparticles. The study offers deep insights about the intratumoral barriers that hinder the active‐targeted nanoparticles delivery, and provides a basis for developing more effective strategies to accelerate the clinical translation of active‐targeted nanomedicines. Sequential regulations of tumor microenvironment by thalidomide and pre‐photodynamic therapy (pre‐PDT) treatments are exploited to achieve synergistic enhancements of tumor accumulation and cancer cell accessibility of epidermal growth factor receptor (EGFR)‐targeted micelle, thereby improve the targeting ability and therapeutic outcome of the active‐targeted nanoparticles.