Precision combination therapy for triple negative breast cancer via biomimetic polydopamine polymer core-shell nanostructures.
Photothermal-based combination therapy using functional nanomaterials shows great promise in eradication of aggressive tumors and improvement of drug sensitivity. The therapeutic efficacy and adverse effects of drug combinations depend on the precise control of timely tumor-localized drug release. Here a polymer-dopamine nanocomposite is designed for combination therapy, thermo-responsive drug release and prevention of uncontrolled drug leakage. The thermo-sensitive co-polymer poly (2-(2-methoxyethoxy) ethyl methacrylate-co-oligo (ethylene glycol) methacrylate)-co-2-(dimethylamino) ethyl methacrylate-b-poly (D, l-lactide-co-glycolide) is constructed into core-shell structured nanoparticles for co-encapsulation of two cytotoxic drugs and absorption of small interfering RNAs against survivin. The drug-loaded nanoparticles are surface-coated with polydopamine which confers the nanoformulation with photothermal activity and protects drugs from burst release. Under tumor-localized laser irradiation, polydopamine generates sufficient heat, resulting in nanoparticle collapse and instant drug release within the tumor. The combination strategy of photothermal, chemo-, and gene therapy leads to triple-negative breast cancer regression, with a decrease in the chemotherapeutic drug dosage to about 1/20 of conventional dose. This study establishes a powerful nanoplatform for precisely controlled combination therapy, with dramatic improvement of therapeutic efficacy and negligible side effects.
CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology (NCNST), 11 Beiyitiao, Zhongguancun, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Yanping
Y
Ding
CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology (NCNST), 11 Beiyitiao, Zhongguancun, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Shishuai
S
Su
CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology (NCNST), 11 Beiyitiao, Zhongguancun, Beijing 100190, China.
Ruirui
R
Zhang
CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology (NCNST), 11 Beiyitiao, Zhongguancun, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Leihou
L
Shao
CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology (NCNST), 11 Beiyitiao, Zhongguancun, Beijing 100190, China; College of Pharmaceutical Science, Jilin University, Changchun 130021, China.
Yinlong
Y
Zhang
CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology (NCNST), 11 Beiyitiao, Zhongguancun, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Bin
B
Wang
CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology (NCNST), 11 Beiyitiao, Zhongguancun, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Yiye
Y
Li
CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology (NCNST), 11 Beiyitiao, Zhongguancun, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Long
L
Chen
Department of Immunohematology, Beijing Institute of Transfusion Medicine, 27 Taiping Road, Beijing 100850, China.
Qun
Q
Yu
CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology (NCNST), 11 Beiyitiao, Zhongguancun, Beijing 100190, China. Electronic address: wuy@nanoctr.cn.
Yan
Y
Wu
CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology (NCNST), 11 Beiyitiao, Zhongguancun, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: niegj@nanoctr.cn.
Guangjun
G
Nie
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D032701:Biomimetics; D001940:Breast / Q000187:drug effects / Q000473:pathology; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy / Q000379:methods; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods; D007211:Indoles / Q000737:chemistry / Q000627:therapeutic use*; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D049329:Nanostructures / Q000737:chemistry / Q000627:therapeutic use; D010789:Phototherapy / Q000379:methods; D011108:Polymers / Q000737:chemistry / Q000627:therapeutic use*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use*; D000067492:RNAi Therapeutics / Q000379:methods; D012097:Repressor Proteins / Q000235:genetics; D000077022:Survivin; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*
D000970:Antineoplastic Agents; C117749:Birc5 protein, mouse; D003692:Delayed-Action Preparations; D007211:Indoles; D051034:Inhibitor of Apoptosis Proteins; D011108:Polymers; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D000077022:Survivin; C568283:polydopamine
Chemotherapy; Photothermal therapy; Small interfering RNA; Spatiotemporal-controlled drug release; Thermo-responsive