Anti-BCMA surface engineered biomimetic photothermal nanomissile enhances multiple myeloma cell apoptosis and overcomes the disturbance of NF-κB signaling in vivo

Xiaojuan Xiao; Zekang Ma; Zhenzhen Li; Yiyi Deng; Yibin Zhang; Ruohong Xiang; Lin Zhu; Yilang He; Hui Li; Yu Jiang; Yu Zhu; Yifang Xie; Hongling Peng; Xifeng Liu; Haiqin Wang; Mao Ye; Yuetao Zhao; Jing Liu

doi:10.1016/j.biomaterials.2023.122096

Anti-BCMA surface engineered biomimetic photothermal nanomissile enhances multiple myeloma cell apoptosis and overcomes the disturbance of NF-κB signaling in vivo

Biomaterials. 2023 Jun:297:122096. doi: 10.1016/j.biomaterials.2023.122096. Epub 2023 Mar 17.

Authors

Xiaojuan Xiao¹, Zekang Ma², Zhenzhen Li², Yiyi Deng², Yibin Zhang³, Ruohong Xiang², Lin Zhu², Yilang He², Hui Li⁴, Yu Jiang², Yu Zhu², Yifang Xie², Hongling Peng², Xifeng Liu², Haiqin Wang², Mao Ye⁵, Yuetao Zhao⁶, Jing Liu⁷

Affiliations

¹ Department of Hematology, The Second Xiangya Hospital; Department of Biochemistry and Molecular Biology, School of Life Sciences; Hunan Province Key Laboratory of Basic and Applied Hematology, Central South University, Changsha, 410011, Hunan, China. Electronic address: xiaojuan_xiao@csu.edu.cn.
² Department of Hematology, The Second Xiangya Hospital; Department of Biochemistry and Molecular Biology, School of Life Sciences; Hunan Province Key Laboratory of Basic and Applied Hematology, Central South University, Changsha, 410011, Hunan, China.
³ Department of Pathology, Xiangya Hospital, Central South University, 410008, Changsha, China.
⁴ Department of Dermatology, Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Clinical Research Center for Cancer Immunotherapy, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
⁵ Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Biosensing and Chemometrics; College of Biology; College of Chemistry and Chemical Engineering, Hunan University, Changsha, 410082, China. Electronic address: goldleaf@hnu.edu.cn.
⁶ Department of Hematology, The Second Xiangya Hospital; Department of Biochemistry and Molecular Biology, School of Life Sciences; Hunan Province Key Laboratory of Basic and Applied Hematology, Central South University, Changsha, 410011, Hunan, China. Electronic address: ytzhao@csu.edu.cn.
⁷ Department of Hematology, The Second Xiangya Hospital; Department of Biochemistry and Molecular Biology, School of Life Sciences; Hunan Province Key Laboratory of Basic and Applied Hematology, Central South University, Changsha, 410011, Hunan, China. Electronic address: liujing2018@csu.edu.cn.

PMID: 37075614
DOI: 10.1016/j.biomaterials.2023.122096

Abstract

Conventional chemotherapy for multiple myeloma (MM) faces the challenges of a low complete remission rate and transformation to recurrence/refractory. The current MM first-line clinical drug Bortezomib (BTZ) faces the problem of enhanced tolerance and nonnegligible side effects. B cell maturation antigen (BCMA), for its important engagement in tumor signaling pathways and novel therapy technologies such as Chimeric antigen receptor T-Cell immunotherapy (CAR-T) and Antibody Drug Conjugate (ADC), has been identified as an ideal target and attracted attention in anti-MM therapy. Emerging nanotechnology provided feasible methods for drug delivery and new therapeutic strategies such as photothermal therapy (PTT). Herein, we developed a BCMA-Targeting biomimetic photothermal nanomissile BTZ@BPQDs@EM @anti-BCMA (BBE@anti-BCMA) by integration of BTZ, black phosphorus quantum dots (BPQDs), Erythrocyte membrane (EM) and BCMA antibody (anti-BCMA). We hypothesized that this engineered nanomissile could attack tumor cells in triple ways and achieve effective treatment of MM. Consequently, the intrinsic biomimetic nature of EM and the active targeting property of anti-BCMA enhanced the accumulation of therapeutic agents in the tumor site. Besides, owing to the decrease in BCMA abundance, the potential apoptosis-inducing ability was revealed. With the support of BPQDs' photothermal effect, Cleaved-Caspase-3 and Bax signal increased significantly, and the expression of Bcl-2 was inhibited. Furthermore, the synergistic photothermal/chemo therapy can effectively inhibit tumor growth and reverse the disorder of NF-κB in vivo. Importantly, this biomimetic nanodrug delivery system and antibody induced synergistic therapeutic strategy efficiently killed MM cells with ignorable systemic toxicity, which is a promising method for the future anticancer treatment of hematological malignancies in clinics.

Keywords: B cell maturation antigen; Biomimetic photothermal nanomedicine; Cell apoptosis; Multiple myeloma; NF-κB.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomimetics
Humans
Immunotherapy, Adoptive / methods
Multiple Myeloma* / pathology
Multiple Myeloma* / therapy
NF-kappa B / metabolism
Receptors, Chimeric Antigen* / metabolism
Receptors, Chimeric Antigen* / therapeutic use
T-Lymphocytes

Substances

Receptors, Chimeric Antigen
NF-kappa B