TY - JOUR
T1 - Multistage targeted “Photoactive neutrophil” for enhancing synergistic photo-chemotherapy
AU - Xu, Yurui
AU - Zhang, Xiaomin
AU - Hu, Getian
AU - Wu, Xiaotong
AU - Nie, Yuanyuan
AU - Wu, Heming
AU - Kong, Desheng
AU - Ning, Xinghai
N1 - Funding Information:
The works were supported by the National Key Research and Development Program of China (Grant No. 2019YFA0802800 ), the National Key Research and Development Program of China (Grant No. 2018YFB1105400 ), National Natural Science Foundation of China (Grant No. 21472090 ), Natural Science Foundation of Jiangsu Province (Grant No. BK20180334 ), Fundamental Research Funds for Central Universities Nanjing University , and Key Research and Development Program of Jiangsu Provincial Department of Science and Technology of China (Nos. BE2019002 ).
Publisher Copyright:
© 2021
PY - 2021/12
Y1 - 2021/12
N2 - Cell-based drug delivery system holds a great promise in anticancer treatment, due to its potential of maximizing therapeutic efficacy while minimizing adverse effects. However, current cell system can only deliver drugs in tumor lesions, but lack an ability to target subcellular locus of therapeutic actions, thereby compromising anticancer efficacy. Herein, we bioengineered living neutrophils as a novel type of “Photoactive neutrophil” (PAN) with capabilities of self-amplified multistage targeting and inflammation response for enhancing mitochondria-specific photo-chemotherapy. PAN encapsulated multifunctional nanocomplex (RA/Ce6) of RGD-apoptotic peptide conjugate (RA) decorated liposomal photosensitizer Ce6, and could overcome tumor barriers to selectively release RA/Ce6 within tumor. Consequently, RA/Ce6 actively entered cancer cells and accumulated in mitochondria to trigger combined photodynamic therapy (PDT) and RA-induced mitochondrial membrane disruption, resulting in enhanced therapeutic effects. Importantly, PAN exhibited inflammation amplified tumor targeting after PDT, and initiated combined photo-chemotherapy to suppress tumor growth without adverse effects, leading to prolonged mice survival. Therefore, PAN represents the first multistage targeted cell therapy, and brings new insights into cancer treatment.
AB - Cell-based drug delivery system holds a great promise in anticancer treatment, due to its potential of maximizing therapeutic efficacy while minimizing adverse effects. However, current cell system can only deliver drugs in tumor lesions, but lack an ability to target subcellular locus of therapeutic actions, thereby compromising anticancer efficacy. Herein, we bioengineered living neutrophils as a novel type of “Photoactive neutrophil” (PAN) with capabilities of self-amplified multistage targeting and inflammation response for enhancing mitochondria-specific photo-chemotherapy. PAN encapsulated multifunctional nanocomplex (RA/Ce6) of RGD-apoptotic peptide conjugate (RA) decorated liposomal photosensitizer Ce6, and could overcome tumor barriers to selectively release RA/Ce6 within tumor. Consequently, RA/Ce6 actively entered cancer cells and accumulated in mitochondria to trigger combined photodynamic therapy (PDT) and RA-induced mitochondrial membrane disruption, resulting in enhanced therapeutic effects. Importantly, PAN exhibited inflammation amplified tumor targeting after PDT, and initiated combined photo-chemotherapy to suppress tumor growth without adverse effects, leading to prolonged mice survival. Therefore, PAN represents the first multistage targeted cell therapy, and brings new insights into cancer treatment.
KW - Bioengineered neutrophil
KW - Combined treatment
KW - Mitochondrial specificity
KW - Multistage targeting
KW - Photo-chemotherapy
UR - http://www.scopus.com/inward/record.url?scp=85117720551&partnerID=8YFLogxK
U2 - 10.1016/j.biomaterials.2021.121224
DO - 10.1016/j.biomaterials.2021.121224
M3 - Article
C2 - 34710792
AN - SCOPUS:85117720551
SN - 0142-9612
VL - 279
JO - Biomaterials
JF - Biomaterials
M1 - 121224
ER -
