Enhanced Precision Therapy of Multiple Myeloma Through Engineered Biomimetic Nanoparticles with Dual Targeting
Ruogu Qi,
Shanshan Wang,
Jiayi Yu,
Tianming Lu,
Zhiqiang Bi,
Weibo Liu,
Yuanyuan Guo,
Yong Bian,
Jianliang Shen,
Xuesong Zhang,
Wenhao Hu
Affiliations
Ruogu Qi
School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China; Corresponding authors.
Shanshan Wang
School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China; Laboratory Animal Center, Nanjing University of Chinese Medicine, Nanjing 210023, China
Jiayi Yu
Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing, Department of Radiation Oncology, Beijing Cancer Hospital, Beijing 100142, China
Tianming Lu
School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
Zhiqiang Bi
School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
Weibo Liu
Department of Orthopedics, The Fourth Medical Center, The Chinese People's Liberation Army General Hospital, Beijing 100853, China
Yuanyuan Guo
School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
Yong Bian
Laboratory Animal Center, Nanjing University of Chinese Medicine, Nanjing 210023, China
Jianliang Shen
State Key Laboratory of Ophthalmology, Optometry and Vision Science, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou 325027, China; Corresponding authors.
Xuesong Zhang
Department of Orthopedics, The Fourth Medical Center, The Chinese People's Liberation Army General Hospital, Beijing 100853, China; Corresponding authors.
Wenhao Hu
Department of Orthopedics, The Fourth Medical Center, The Chinese People's Liberation Army General Hospital, Beijing 100853, China; Corresponding authors.
Multiple myeloma (MM) is the second most prevalent hematological malignancy. Current MM treatment strategies are hampered by systemic toxicity and suboptimal therapeutic efficacy. This study addressed these limitations through the development of a potent MM-targeting chemotherapy strategy, which capitalized on the high binding affinity of alendronate for hydroxyapatite in the bone matrix and the homologous targeting of myeloma cell membranes, termed T-PB@M. The results from our investigations highlight the considerable bone affinity of T-PB@M, both in vitro and in vivo. Additionally, this material demonstrated a capability for drug release triggered by low pH conditions. Moreover, T-PB@M induced the generation of reactive oxygen species and triggered cell apoptosis through the poly(ADP-ribose) polymerase 1 (PARP1)–Caspase-3–B-cell lymphoma-2 (Bcl-2) pathway in MM cells. Notably, T-PB@M preferentially targeted bone-involved sites, thereby circumventing systemic toxic side effects and leading to prolonged survival of MM orthotopic mice. Therefore, this designed target-MM nanocarrier presents a promising and potentially effective platform for the precise treatment of MM.
