Abstract：
The therapeutic efficacy of camptothecin (CPT), a potent antitumor alkaloid, is hindered by its hydrophobic nature and instability, limiting its clinical use in treating cutaneous squamous cell carcinoma (SCC). This study introduces a novel nano drug delivery system (NDDS) utilizing functionalized mesoporous silica nanoparticles (FMSNs) for efficient CPT delivery. The FMSNs were loaded with CPT and subsequently coated with chitosan (CS) for enhanced stability and bioadhesion. Importantly, CpG oligodeoxynucleotide (CpG ODN) was attached onto the CS-coated FMSNs to leverage the immunostimulatory properties of CpG ODN, augmenting the chemotherapy\'s efficacy. The final formulation FMSN-CPT-CS-CpG displayed an average size of 241 nm and PDI of 0.316 with an encapsulation efficiency of 95 %. Comprehensive in vitro and in vivo analyses, including B16F10 cells and DMBA/TPA-induced SCC murine model, demonstrated that the FMSN-CPT-CS-CpG formulation significantly enhanced cytotoxicity against B16F10 cells and induced complete regression in 40 % of the in vivo subjects, surpassing the efficacy of standard CPT and FMSN-CPT treatments. This study highlights the potential of combining chemotherapeutic and immunotherapeutic agents in an NDDS for targeted, efficient skin cancer treatment.
摘要：
喜树碱（CPT）的治疗效果，一种有效的抗肿瘤生物碱，受到其疏水性质和不稳定性的阻碍，限制了其在治疗皮肤鳞状细胞癌（SCC）中的临床使用。这项研究介绍了一种新型的纳米药物递送系统（NDDS），利用功能化的介孔二氧化硅纳米颗粒（FMSNs）进行有效的CPT递送。用CPT加载FMSN,随后用壳聚糖(CS)包被以增强稳定性和生物粘附性。重要的是,CpG寡脱氧核苷酸（CpGODN）连接到CS包被的FMSN上，以利用CpGODN的免疫刺激特性，增强化疗的疗效。最终制剂FMSN-CPT-CS-CpG显示出241nm的平均尺寸和0.316的PdI,包封效率为95%。全面的体外和体内分析，包括B16F10细胞和DMBA/TPA诱导的SCC小鼠模型，证明了FMSN-CPT-CS-CpG制剂显着增强了对B16F10细胞的细胞毒性，并在40％的体内受试者中诱导了完全消退，超越标准CPT和FMSN-CPT治疗的疗效。这项研究强调了在NDDS中联合化疗和免疫治疗剂的潜力，有效的皮肤癌治疗。
