Department of Pharmacy, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China.
College of Pharmacy, Southwest Minzu University, Chengdu 610000, China.
Acta Biomater. 2022 Sep 1;149:321-333. doi: 10.1016/j.actbio.2022.06.033. Epub 2022 Jun 30.
B-cell lymphoma is one of the most common types of lymphoma, and chemotherapy is still the current first-line treatment. However, due to the systemic side effects caused by chemotherapy drugs, traditional regimens have limitations and are difficult to achieve ideal efficacy. Recent studies have found that CD22 (also known as Siglec-2), as a specific marker of B-cells, is significantly up-regulated on B-cell lymphomas. Inspired by the specific recognition and binding of sialic acid residues by CD22, a polysialic acid (PSA)-modified PLGA nanocarrier (SAPC NP) designed to target B-cell lymphoma was fabricated. Mitoxantrone (MTO) was further loaded into SAPC NP through hydrophobic interactions to obtain polysialylated immunogenic cell death (ICD) nanoinducer (MTO@SAPC NP). Cellular experiments confirmed that MTO@SAPC NP could be specifically taken up by two types of CD22 B lymphoma cells including Raji and Ramos cells, unlike the poor endocytic performance in other lymphocytes or macrophages. MTO@SAPC NP was determined to enhance the ICD and show better apoptotic effect on CD22 cells. In the mouse model of B-cell lymphoma, MTO@SAPC NP significantly reduced the systemic side effects of MTO through lymphoma targeting, then achieved enhanced anti-tumor immune response, better tumor suppressive effect, and improved survival rate. Therefore, the polysialylated ICD nanoinducer provides a new strategy for precise therapy of B-cell lymphoma. STATEMENT OF SIGNIFICANCE: • Polysialic acid functionalized nanocarrier (SAPC NP) was designed and prepared. • SAPC NP is specifically endocytosed by two CD22 B lymphoma cells. • Mitoxantrone-loaded nanoinducer (MTO@SAPC NP) promote immunogenic cell death and anti-tumor immune response. • "Polysialylation" is a potential new approach for precision treatment of B-cell lymphoma.
B 细胞淋巴瘤是最常见的淋巴瘤类型之一，化疗仍然是目前的一线治疗方法。然而，由于化疗药物引起的全身副作用，传统方案存在局限性，难以达到理想的疗效。最近的研究发现，CD22（也称为 Siglec-2）作为 B 细胞的特异性标志物，在 B 细胞淋巴瘤上显著上调。受 CD22 对唾液酸残基的特异性识别和结合的启发，设计了一种针对 B 细胞淋巴瘤的多涎酸（PSA）修饰的 PLGA 纳米载体（SAPC NP）。通过疏水相互作用进一步将米托蒽醌（MTO）装载到 SAPC NP 中，得到多涎酸化免疫原性细胞死亡（ICD）纳米诱导剂（MTO@SAPC NP）。细胞实验证实，MTO@SAPC NP 可以被两种类型的 CD22 B 淋巴瘤细胞（包括 Raji 和 Ramos 细胞）特异性摄取，而不是在其他淋巴细胞或巨噬细胞中摄取不良。MTO@SAPC NP 被确定可增强 ICD，并对 CD22 细胞显示出更好的凋亡作用。在 B 细胞淋巴瘤小鼠模型中，MTO@SAPC NP 通过淋巴瘤靶向显著降低了 MTO 的全身副作用，从而增强了抗肿瘤免疫反应，更好地抑制肿瘤生长，提高了存活率。因此，多涎酸化 ICD 纳米诱导剂为 B 细胞淋巴瘤的精准治疗提供了一种新策略。
