Abstract
Dacarbazine (DTIC) dominates chemotherapy for malignant melanoma (MM). However, the hydrophobicity, photosensitivity, instability, and toxicity to normal cells of DTIC limit its efficacy in treating MM. In the present study, we constructed star-shaped block polymers nanoparticles (NPs) based on Cholic acid -poly (lactide-co-glycolide)-b-polyethylene glycol (CA-PLGA-b-PEG) for DTIC encapsulation and MM targeted therapy. DTIC-loaded CA-PLGA-b-PEG NPs (DTIC-NPs) were employed to increase the drug loading and achieve control release of DTIC, followed by further modification with nucleic acid aptamer AS1411 (DTIC-NPs-Apt), which played an important role for active targeted therapy of MM. In vitro, DTIC-NPs-Apt showed good pH-responsive release and the strongest cytotoxicity to A875 cells compared with DTIC-NPs and free DTIC. In vivo results demonstrated that the versatile DTIC-NPs-Apt can actively target the site of MM and exhibited excellent anti-tumor effects with no obvious side effects. Overall, this research provided multi-functional NPs, which endow a new option for the treatment of MM.
Highlights
Malignant melanoma (MM) is one of the most life-threatening malignancies (Li et al, 2015; Liu et al, 2017)
The average survival time of patients with MM is about 8–9 months, and overall survival rate is less than 15% with 3 years (Balch et al, 2009)
DTIC has limited efficacy in treating melanoma due to its Nanoparticles for Malignant Melanoma Therapy hydrophobicity and short half-life (Tagne et al, 2008; Koyama et al, 2016) In addition, DTIC has photosensitivity and instability, which increase the difficulty of drug storage and transportation
Summary
Malignant melanoma (MM) is one of the most life-threatening malignancies (Li et al, 2015; Liu et al, 2017). Tumor active targeted drug therapy based on nanoparticles (NPs) drug delivery systems achieved the most success. AS1411 can bind to nucleolin, which was highly expressed on the surface of tumor cells, to achieve the purpose of targeted therapy (Destouches et al, 2011; Ding et al, 2011). Starshaped block polymers based on Poly (lactide-co-glycolide) (PLGA) is a simple example of highly specific targeting carrier material. They are branched polymer with all branches extending from a single core, which endow them a higher drug loading capacity and encapsulation efficiency than linear polymers with the same molar mass (Nguyen-Van et al, 2011; Ma et al, 2013; Tao et al, 2014; Peng et al, 2018; Liu et al, 2019). The results show the NPs exhibited an excellent anti-tumor effect, providing a new option for MM patients
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