Chueahongthong Fah, Chiampanichayakul Sawitree, Viriyaadhammaa Natsima, Dejkriengkraikul Pornngarm, Okonogi Siriporn, Berkland Cory, Anuchapreeda Songyot
Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand.
Department of Medical Technology, School of Allied Health Sciences, University of Phayao, Phayao 56000, Thailand.
Polymers (Basel). 2024 Sep 2;16(17):2498. doi: 10.3390/polym16172498.
A targeted micellar formation of doxorubicin (Dox) and curcumin (Cur) was evaluated to enhance the efficacy and reduce the toxicity of these drugs in KG1a leukemic stem cells (LSCs) compared to EoL-1 leukemic cells. Dox-Cur-micelle (DCM) was developed to improve the cell uptake of both compounds in LSCs. Cur-micelle (CM) was produced to compare with DCM. DCM and CM were conjugated with two FLT3 (FMS-like tyrosine kinase)-specific peptides (CKR; C and EVQ; E) to increase drug delivery to KG1a via the FLT3 receptor (AML marker). They were formulated using a film-hydration technique together with a pH-induced self-assembly method. The optimal drug-to-polymer weight ratios for the DCM and CM formulations were 1:40. The weight ratio of Dox and Cur in DCM was 1:9. DCM and CM exhibited a particle size of 20-25 nm with neutral charge and a high %EE. Each micelle exhibited colloidal stability and prolonged drug release. Poloxamer 407 (P407) was modified with terminal azides and conjugated to FLT3-targeting peptides with terminal alkynes. DCM and CM coupled with peptides C, E, and C + E exhibited a higher particle size. Moreover, DCM-C + E and CM-C + E showed the highest toxicity in KG-1a and EoL-1 cells. Using two peptides likely improves the probability of micelles binding to the FLT3 receptor and induces cytotoxicity in leukemic stem cells.
评估了阿霉素（Dox）和姜黄素（Cur）的靶向胶束形成，以增强这些药物在KG1a白血病干细胞（LSC）中的疗效并降低其毒性，与EoL-1白血病细胞进行比较。开发了Dox-Cur-胶束（DCM）以提高这两种化合物在LSC中的细胞摄取。制备了Cur-胶束（CM）以与DCM进行比较。DCM和CM与两种FLT3（FMS样酪氨酸激酶）特异性肽（CKR；C和EVQ；E）偶联，以增加通过FLT3受体（AML标志物）向KG1a的药物递送。它们采用薄膜水化技术和pH诱导的自组装方法进行配制。DCM和CM制剂的最佳药物与聚合物重量比为1:40。DCM中Dox和Cur的重量比为1:9。DCM和CM的粒径为20-25nm，电荷中性，包封率高。每个胶束都表现出胶体稳定性和延长的药物释放。泊洛沙姆407（P407）用末端叠氮化物修饰，并与带有末端炔烃的FLT3靶向肽偶联。与肽C、E和C + E偶联的DCM和CM表现出更大的粒径。此外，DCM-C + E和CM-C + E在KG-1a和EoL-1细胞中表现出最高的毒性。使用两种肽可能会提高胶束与FLT3受体结合的概率，并诱导白血病干细胞的细胞毒性。
