title: DR5 mAb-conjugated, DTIC-loaded immuno-nanoparticles effectively and specifically kill malignant melanoma cells in vivo.
abstract: We combined chemo- and immunotherapies by constructing dual therapeutic function immuno-nanoparticles (NPs) consisting of death receptor 5 monoclonal antibody (DR5 mAb)-conjugated nanoparticles loaded with dacarbazine (DTIC) (DTIC-NPs-DR5 mAb). We determined the in vivo targeting specificity of DTIC-NPs-DR5 mAb by evaluating distribution in tumor-bearing nude mice using a real-time imaging system. Therapeutic efficacy was assessed in terms of its effect on tumor volume, survival time, histomorphology, microvessel density (MVD), and apoptotic index (AI). Systemic toxicity was evaluated by measuring white blood cells (WBC) counts, alanine aminotransferase (ALT) levels, and creatinine clearance (CR).In vivo and ex vivo imaging indicates that DR5 mAb modification enhanced the accumulation of NPs within the xenograft tumor. DTIC-NPs-DR5 mAb inhibited tumor growth more effectively than DTIC or DR5 mAb alone, indicating that combining DTIC and DR5 mAb through pharmaceutical engineering achieves a better therapeutic effect. Moreover, the toxicity of DTIC-NPs-DR5 mAb was much lower than that of DTIC, implying that DR5 mAb targeting reduces nonspecific uptake of DTIC into normal tissue and thus decreases toxic side effects. These results demonstrate that DTIC-NPs-DR5 mAb is a safe and effective nanoparticle formulation with the potential to improve the efficacy and specificity of melanoma treatment.
authors: Department of Pharmaceutics, Medical College of Jiaxing University, Jiaxing, PR China.|Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, PR China.|Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, USA.
authors: Baoyue
authors: B
authors: Ding
authors: Department of Pharmaceutics, Shanghai Pulmonary Hospital, Tongji University, Shanghai, PR China.
authors: Wei
authors: W
authors: Zhang
authors: Department of Pharmaceutics, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, PR China.
authors: Xin
authors: X
authors: Wu
authors: Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, USA.
authors: Jeffrey
authors: J
authors: Wang
authors: Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, USA.
authors: Chen
authors: C
authors: Xie
authors: Department of Pharmaceutics, Medical College of Jiaxing University, Jiaxing, PR China.
authors: Xuan
authors: X
authors: Huang
authors: Department of Pharmaceutics, Medical College of Jiaxing University, Jiaxing, PR China.
authors: Shuyu
authors: S
authors: Zhan
authors: Department of Pharmaceutics, Medical College of Jiaxing University, Jiaxing, PR China.
authors: Yongxia
authors: Y
authors: Zheng
authors: Department of Pharmaceutics, Medical College of Jiaxing University, Jiaxing, PR China.
authors: Yueyan
authors: Y
authors: Huang
authors: Department of Pharmaceutics, Medical College of Jiaxing University, Jiaxing, PR China.
authors: Ningyin
authors: N
authors: Xu
authors: Department of Pharmaceutics, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, PR China.
authors: Xueying
authors: X
authors: Ding
authors: Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, PR China.
authors: Shen
authors: S
authors: Gao
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D017209:Apoptosis; D045744:Cell Line, Tumor; D003404:Creatinine / Q000378:metabolism; D003606:Dacarbazine / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems; D006801:Humans; D007167:Immunotherapy; D007962:Leukocytes / Q000187:drug effects; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D009368:Neoplasm Transplantation; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000737:chemistry*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; C505639:TNFRSF10B protein, human; D003606:Dacarbazine; D003404:Creatinine; D000410:Alanine Transaminase
keywords: DR5 monoclonal antibodies; active targeting nanoparticles; chemoimmunotherapy; dacarbazine; malignant melanoma